ETHNOPHARMACOLOGICAL RELEVANCE:Ligusticum chuanxiong Hort (LCH), with the accepted name of Ligusticum striatum DC in "The Plant List" database, is a widely used ethnomedicine in treating ischemic stroke, and borneol (BO) is usually prescribed with LCH for better therapy. Our previous study confirmed their synergistic effect on neurogenesis against cerebral ischemia. However, the underlying mechanism is still unclear. AIM OF THE STUDY:More and more evidence indicated that astrocytes (ACs) might be involved in the modulation of neurogenesis via polarization reaction. The study was designed to explore the synergic mechanism between LCH and BO in promoting astrocyte-mediated neurogenesis. MATERIALS AND METHODS:After primary cultures and identifications of ACs and neural stem cells (NSCs), the oxygen-glucose deprivation (OGD) model and the concentrations of LCH and BO were optimized. After the OGD-injured ACs were treated by LCH, BO, and their combination, the conditioned mediums were used to culture the OGD-injured NSCs. The proliferation, migration, and differentiation of NSCs were assessed, and the secretions of BDNF, CNTF, and VEGF from ACs were measured. Then the expressions of C3 and PTX3 were detected. Moreover, the mice were performed a global cerebral ischemia/reperfusion model and treated with LCH and (or) BO. After the assessments of Nissl staining, the expressions of Nestin, DCX, GFAP, C3, PTX3, p65 and p-p65 were probed. RESULTS:The most appropriate duration of OGD for the injury of both NSCs and ACs was 6 h, and the optimized concentrations of LCH and BO were 1.30 μg/mL and 0.03 μg/mL, respectively. The moderate OGD environment induced NSCs proliferation, migration, astrogenesis, and neurogenesis, increased the secretions of CNTF and VEGF from ACs, and upregulated the expressions of C3 and PTX3. For the ACs, LCH further increased the secretions of BDNF and CNTF, enhanced PTX3 expression, and reduced C3 expression. Additionally, the conditioned medium from LCH-treated ACs further enhanced NSC proliferation, migration, and neurogenesis. The in vivo study showed that LCH markedly enhanced the Nissl score and neurogenesis, and decreased astrogenesis which was accompanied by downregulations of C3, p-p65, and p-p65/p65 and upregulation of PTX3. BO not only decreased the expression of C3 in ACs both in vitro and in vivo but also downregulated p-p65 and p-p65/p65 in vivo. Additionally, BO promoted the therapeutic effect of LCH for most indices. CONCLUSION:A certain degree of OGD might induce ACs to stimulate the proliferation, astrogenesis, and neurogenesis of NSCs. LCH and BO exhibited a marked synergy in promoting ACs-mediated neurogenesis and reducing astrogenesis, in which LCH played a dominant role and BO boosted the effect of LCH. The mechanism of LCH might be involved in switching the polarization of ACs from A1 to A2, while BO preferred to inhibit the formation of A1 phenotype via downregulating NF-κB pathway.

Ethnopharmacological relevance: Ligusticum striatum DC., also known as Ligusticum chuanxiong Hort. (LCH), is widely used in China for its excellent effect in ischaemic stroke (IS) patients, and borneol (BO) has been confirmed to maintain the blood-brain barrier (BBB) after stroke. They are often used as a combination in the prescriptions of IS patients. Although the advantage of their combined treatment in improving brain ischaemia has been verified, their synergistic mechanism on BBB maintenance is still unclear.Aim of the study: This study was designed to evaluate the synergistic effect of maintaining the BBB between LCH and BO against IS and to further explore the potential mechanism.Materials and methods: After primary mouse brain microvascular endothelial cells (BMECs) were extracted and identified, the duration of oxygen-glucose deprivation (OGD) and the doses of LCH and BO were optimized. Then, the cells were divided into five groups: control, model, LCH, BO, and LCH + BO. Cell viability, injury degree, proliferation and migration were detected by CCK-8, LDH, EdU and wound-healing assays, respectively. Hoechst 33342 staining was adopted to detect the apoptosis rate, and western blotting was employed to observe the expressions of Bax, Bcl-2, caspase-3 and cleaved caspase-3. The TEER value and NaF permeability were measured to assess tight junction (TJ) function, while ZO-1, occludin and claudin-5 were also probed by western blotting. Moreover, the HIF-1 alpha/VEGF pathway was observed to explore the underlying mechanism of BBB maintenance. In vivo, global cerebral ischaemia/reperfusion (GCIR) surgery was performed to establish an IS model. After treatment with LCH (200 mg/kg) and/or BO (160 mg/kg), histopathological structure and BMECs repair were observed by HE staining and immunohistochemistry of vWF. Meanwhile, TJ-associated proteins in vivo were also detected by western blotting. Results: Basically, LCH and BO had different emphases. LCH significantly attenuated the vacuolar structure, nuclear pyknosis and neuronal loss of GCIR mice, while BO focused on promoting BMECs proliferation and angiogenesis and inhibiting the degradation of TJ-associated proteins in vivo after IS. Interestingly, their combination further enhanced these effects. OGD injury markedly reduced the viability, proliferation and migration of primary BMECs; decreased the ratio of Bcl-2/Bax, TEER value, and the expressions of ZO-1, occludin and claudin-5; induced LDH release and apoptosis; and increased the cleaved caspase-3/caspase-3 ratio and NaF permeability. Meanwhile, BO might be the main contributor to the combinative treatment in ameliorating OGDinduced damage of BMECs and degradation of TJ-related proteins, and the potential mechanism might be involved in upregulating the HIF-1 alpha/VEGF signalling pathway. Although LCH showed no obvious improvement, it could enhance the therapeutic effect of BO. Interestingly, their combination even produced some new improvements, including the reduction of cleaved caspase-3 and increase in TEER value, none of which were exhibited in their monotherapies.

We conducted in this paper a regression analysis of factors associated with acute radiation pneumonia due to radiation therapy for lung cancer utilizing cluster analysis to explore the predictive effects of clinical and dosimetry factors on grade ≥2 radiation pneumonia due to radiation therapy for lung cancer and to further refine the effect of the ratio of the volume of the primary foci to the volume of the lung lobes in which they are located on radiation pneumonia, to refine the factors that are clinically effective in predicting the occurrence of grade ≥2 radiation pneumonia. This will provide a basis for better guiding lung cancer radiation therapy, reducing the occurrence of grade ≥2 radiation pneumonia, and improving the safety of radiotherapy. Based on the characteristics of the selected surveillance data, the experimental simulation of the factors of acute radiation pneumonia due to lung cancer radiation therapy was performed based on three signal detection methods using fuzzy mean clustering algorithm with drug names as the target and adverse drug reactions as the characteristics, and the drugs were classified into three categories. The method was then designed and used to determine the classification correctness evaluation function as the best signal detection method. The factor classification and risk feature identification of acute radiation pneumonia due to radiation therapy for lung cancer based on ADR were achieved by using cluster analysis and feature extraction techniques, which provided a referenceable method for establishing the factor classification mechanism of acute radiation pneumonia due to radiation therapy for lung cancer and a new idea for reuse of ADR surveillance report data resources.

Background: Ligusticum chuanxiong Hort (LCH) is a famous ethnomedicine in Asia known for its excellent output on stroke treatment, and borneol usually acts as an assistant for its reducing permeability of the blood–brain barrier (BBB) after stroke. Although their synergy against brain ischemia was verified in previous studies, the potential mechanism is still unknown. Methods: The research aimed to explore the exact synergic mechanisms between LCH and borneol on neurogenesis within the areas of the dentate gyrus and subventricular zone. After treating middle cerebral artery occlusion rats with LCH (0.1 g/kg) and/or borneol (0.08 g/kg), the neurological severity score, brain infarct ratio, Nissl staining, Evans blue permeability, BBB ultrastructure, and expressions of von Willebrand factor and tight junction–associated proteins were measured. Co-localizations of Nestin+/BrdU+ and doublecortin+/BrdU+, and expressions of neuronal nuclei (NeuN) and glial fibrillary acidic protein (GFAP) were observed under a fluorescence microscope. Moreover, astrocyte polarization markers of complement component 3 and pentraxin 3, and relevant neurotrophins were also detected by immunoblotting. Results: Basically, LCH and borneol had different focuses, although both of them decreased infarct areas, and increased quantity of Nissl bodies and expression of brain-derived neurotrophic factor. LCH increased the neurological severity score, NeuN+ cells, and the ratios of Nestin+/BrdU+ and doublecortin+/BrdU+, and decreased GFAP+ cells and ciliary neurotrophic factor expression. Additionally, it regulated the expressions of complement component 3 and pentraxin 3 to transform astrocyte phenotypes. Borneol improved BBB ultrastructure and increased the expressions of von Willebrand factor, tight junction–associated proteins, vascular endothelial growth factor, and vascular endothelial growth factor receptor 2. Unexpectedly, their combined therapy showed more obvious regulations on the Nissl score, Evans blue permeability, doublecortin+/BrdU+, NeuN+ cells, brain-derived neurotrophic factor, and vascular endothelial growth factor than both of their monotherapies. Conclusions: The results indicated that LCH and borneol were complementary to each other in attenuating brain ischemia by and large. LCH mainly promoted neural stem cell proliferation, neurogenesis, and mature neuron preservation, which was probably related to the transformation of reactive astrocytes from A1 subtype to A2, while borneol preferred to maintain the integrity of the BBB, which provided neurogenesis with a homeostatic environment.

The vascular eendothelial cells are highly heterogeneous and associated with numerous diseases. Thymosin β4 (Tβ4) plays pleiotropic roles in endothelial cell differentiation, migration and angiogenesis. However, the underlying mechanisms played by Tβ4 in the regulation of endothelial cells have not yet been well investigated. In the present study, Tβ4 -GFP adenovirus, transfected into human umbilical vein endothelial cells (HUVECs), and cell morphology were analyzed by fluorescence microscopy. ELISA was used to determine the concentration of Tβ4 expression. Furthermore, the effects of Tβ4 overexpression on HUVECs proliferation, apoptosis and migration were investigated. Real-time quantitative PCR and western blot were conducted to examine mRNA and protein expression in HUVECs with Tβ4 overexpression. Moreover, the underlying molecular mechanism of Tβ4 in HUVECs function was tested through treatment with LY294002, a PI3K/AKT inhibitor. Overexpression of Tβ4 increased the cell ability of HUVECs, and up-regulated the expression of the proliferation markers PCNA and Cyclin D1. In addition, overexpression of Tβ4 reduced HUVECs apoptosis, both under normoxic and hypoxic conditions. Moreover, overexpression of Tβ4 increased the ability of HUVECs to migrate through the membrane and up-regulated levels of MMP-2 and MMP-9. The use of LY294002 decreased the p-AKT (Ser473) level, which was induced by Tβ4 overexpression. Importantly, LY294002 reduced Tβ4-induced HUVECs proliferation and migration. In conclusion, our results suggest that Tβ4 is a major regulator of HUVECs function by activating the AKT signaling pathway.

Background and Objective: Ligusticum chuanxiong Hort (LC) and borneol (BO) are usually prescribed as a combination of ischemic stroke patients for a better therapeutic effect in China. However, their synergic mechanism is unclear. Considering the critical role of Brain Microvascular Endothelial Cells (BMECs) in this disorder, the present study was designed to explore their synergic mechanism in protecting BMECs against Oxygen-Glucose Deprivation/Reperfusion (OGD/R) injury. Materials and Methods: The primary cultured BMECs were identified and divided into 5 groups of control, model, ELC (50 mg L-1), BO (50 mu g L-1) and ELC+BO. Then their synergic treatment was evaluated via measuring oxidative stress, [Ca2+]i, apoptosis ratio, levels of apoptosis-related genes and angiogenesis-related proteins. Results: After a comparison between the combined group and their monotherapies, it was shown that the superiority of ELC was in inhibiting oxidative stress and apoptosis, regulating [Ca2+]i and levels of apoptosis-related genes, while that of BO was in promoting angiogenesis. Interestingly, the combined therapy even reduced VEGFR1 expression which was unaffected in both of their monotherapies. Conclusion: ELC and BO might play different roles in protecting BMECs against oxygen-glucose deprivation/reperfusion injury and their synergic effect was displayed in the present study.

Being applicable to the technical field of medicine, the invention provides a pharmaceutical composition for treating cerebral arterial thrombosis related diseases. The pharmaceutical composition comprises: 3-7 parts of total saponins of codonopsis pilosula, 4-8 parts of senkyunolide I and 10-15 parts of borneol. The pharmaceutical composition provided by the invention is simple in formula, economical and practical, complementary, and reasonable in compatibility, and can effectively treat cerebral arterial thrombosis. Moreover, the components are all from natural products, and no adverse reaction, toxic or side effect is generated after long-term use, therefore the pharmaceutical composition is worthy of popularization and application. According to the preparation method of the pharmaceutical composition provided by the invention, the components in the formula ratio are uniformly mixed and then are mixed with pharmaceutically acceptable auxiliary materials so as to obtain the pharmaceutical preparation. The method is simple, convenient to operate, and is suitable for large-scale production.

BACKGROUND:Obstructive sleep apnea (OSA) is associated with many cardiovascular disorders. Intermittent hypoxia (IH) is a key pathological hallmark of OSA. This study was conducted to evaluate the potential therapeutic effects and the associated mechanisms of adiponectin (APN) on IH induced human adult cardiac myocytes (HACMs) injury. MATERIAL AND METHODS:HACMs were exposed to normoxia or IH (1% to 21% O₂) using a novel cell culture bio-reactor with gas-permeable membranes. Cell viability was detected by Cell Counting Kit-8 assay. Cell membrane integrity was assessed by the detection of lactate dehydrogenase (LDH) release. Cell apoptosis was analyzed by flow cytometry. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were determined using specific assay kits. P-AMPK (AMP-activated protein kinase), p-LKB1, and p-p65 protein levels were measured by western blotting. Pro-inflammatory factors including interleukin (IL)-1β, IL-6, IL-8 expressions were detected by enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction. RESULTS:The results showed that APN had no cytotoxic to HACMs. Compared with the control group, HACMs cell viability significantly decreased, LDH release increased and cell apoptosis increased in the IH group. The levels of IL-1β, IL-6, IL-8, MDA, and p-p65 were higher, while the levels of SOD, GSH-Px, p-AMPK, and p-LKB1 were lower in HACMs cells in the IH group than that in the control group. However, APN treatment significantly rescued these effects compared with the IH group in a dose-dependent manner. CONCLUSIONS:In conclusion, these results indicated that APN protected against IH induced HACMs injury possibly mediated by AMPK and NF-κB pathway.

Background: In the present study, we aimed to investigate the effects of sinomenine (SIN) on chronic intermittent hypoxia (CIH)-induced lung injury in rats, and to explore the underlying mechanisms. Material/Methods: To perform the investigation, a CIH rat model was established. ELISA assay was applied to detect the level of inflammatory cytokines. Oxidative stress bio-markers (MDA, SOD, and CAT) were determined in lung tissues. In addition, the expression level of NADPH oxidase 2 (Nox2) was analyzed by Western blotting and qRT-PCR, respectively. Results: The results showed that compared with other groups, more obvious pulmonary pathological changes were observed in the CIH group. The level of inflammatory cytokines in the CIH group was markedly higher than that in the control and Con-S groups. Compared with the control and Con-S groups, oxidative stress was notably increased in the CIH group. Expression of Nox2 was also increased in the CIH group. The effects caused by CIH in rats were attenuated by SIN treatment. Conclusions: SIN can reverse chronic intermittent hypoxia-induced lung injury through inhibiting inflammation and oxidative stress.

The current study was carried out to assess the effects of chronic intermittent hypoxia (CIH) on the kidney, the intervention roles of adiponectin (Ad), and the associated mechanisms.

SESSION TITLE: Sleep Disorders: Effects of Intermittent HypoxiaSESSION TYPE: Original Investigation SlidePRESENTED ON: Sunday, April 17, 2016 at 04:00 PM - 05:00 PMPURPOSE: To investigate the effects of chronic intermittent hypoxia (CIH) on genioglossal contractile properties, the intervention role of adiponectin (Ad) and associated mechanisms.METHODS: Thirty-nine healthy Wistar rats were randomly divided into 3 groups, normal control (NC) group, CIH group and CIH+Ad group with 13 rats in each. Rats in NC group were kept breathing normal air, while rats in both CIH and CIH+Ad groups were exposed to same CIH environment (8h/day for successive 35 days). Rats in CIH+Ad group were given intravenous Ad supplement. After CIH exposure, the levels of serum Ad and genioglossus contractile properties, number and structure of mitochondia as well as fiber type of genioglossus were compared among different groups.RESULTS: The following findings were deteced a) Serum Ad level was the lowest in CIH group but the highest in NC group with CIH+ad group in between (all P<0.05) b) Twitch tension, time to peak tension, half relaxation time and tetanic tension were significantly lower in CIH group than those in NC group (P<0.01). Those contractile properties were improved in CIH+Ad group (P<0.05).c) Tetanic fatigue indexes of three groups were decreased more rapidly in the first 20 seconds than those in the following 100 seconds. Tetanic fatigue indexes in NC and CIH+Ad groups were significantly higher than that in CIH group. d) Compared with control group, in CIH group, mitochondrial number was significantly reduced and structure was remarkably impaired, In addition, there was a significant decrease in expression of pathway protein of LKB1-AMPK-PGC1-α. The above changes in CIH group was significantly improved in CIH+Ad group.CONCLUSIONS: CIH could lead to hypoadiponectinemia, impaired genioglossus contractile properties in rats. Such changes might be associated with the CIH induced mitochondrial impairment and muscular fiber type changes. Supplement of adiponectin could improved CIH induced pathological changes.CLINICAL IMPLICATIONS: Choronic intermittent hypoxia (CIH) and upper airway dilating muscle dysfunction were considered as the key pathological changes in obstructive sleep apnea. Genioglossus was also the key dilating muscle in upper airway. The correlation between CIH and genioglosal impairment need to be elucidated. By investogating the coorelation betewwn CIH and genioglossus as well as the possible protective role of adiponectin (Ad), The current study was carried out to explore the pathogenesis of obstructive sleep apnea and possible novel therapy.DISCLOSURE: The following authors have nothing to disclose: Xilong Zhang, Hanpeng Huang, Xiaofeng ZhangNo Product/Research Disclosure Information SESSION TITLE: Sleep Disorders: Effects of Intermittent Hypoxia SESSION TYPE: Original Investigation Slide PRESENTED ON: Sunday, April 17, 2016 at 04:00 PM - 05:00 PM PURPOSE: To investigate the effects of chronic intermittent hypoxia (CIH) on genioglossal contractile properties, the intervention role of adiponectin (Ad) and associated mechanisms. METHODS: Thirty-nine healthy Wistar rats were randomly divided into 3 groups, normal control (NC) group, CIH group and CIH+Ad group with 13 rats in each. Rats in NC group were kept breathing normal air, while rats in both CIH and CIH+Ad groups were exposed to same CIH environment (8h/day for successive 35 days). Rats in CIH+Ad group were given intravenous Ad supplement. After CIH exposure, the levels of serum Ad and genioglossus contractile properties, number and structure of mitochondia as well as fiber type of genioglossus were compared among different groups. RESULTS: The following findings were deteced a) Serum Ad level was the lowest in CIH group but the highest in NC group with CIH+ad group in between (all P<0.05) b) Twitch tension, time to peak tension, half relaxation time and tetanic tension were significantly lower in CIH group than those in NC group (P<0.01). Those contractile properties were improved in CIH+Ad group (P<0.05).c) Tetanic fatigue indexes of three groups were decreased more rapidly in the first 20 seconds than those in the following 100 seconds. Tetanic fatigue indexes in NC and CIH+Ad groups were significantly higher than that in CIH group. d) Compared with control group, in CIH group, mitochondrial number was significantly reduced and structure was remarkably impaired, In addition, there was a significant decrease in expression of pathway protein of LKB1-AMPK-PGC1-α. The above changes in CIH group was significantly improved in CIH+Ad group. CONCLUSIONS: CIH could lead to hypoadiponectinemia, impaired genioglossus contractile properties in rats. Such changes might be associated with the CIH induced mitochondrial impairment and muscular fiber type changes. Supplement of adiponectin could improved CIH induced pathological changes. CLINICAL IMPLICATIONS: Choronic intermittent hypoxia (CIH) and upper airway dilating muscle dysfunction were considered as the key pathological changes in obstructive sleep apnea. Genioglossus was also the key dilating muscle in upper airway. The correlation between CIH and genioglosal impairment need to be elucidated. By investogating the coorelation betewwn CIH and genioglossus as well as the possible protective role of adiponectin (Ad), The current study was carried out to explore the pathogenesis of obstructive sleep apnea and possible novel therapy. DISCLOSURE: The following authors have nothing to disclose: Xilong Zhang, Hanpeng Huang, Xiaofeng Zhang No Product/Research Disclosure Information

Objectives: To investigate role of adiponectin (Ad) in intermittent hypoxia(CIH) induced genioglossal contractile dysfunction. Methods: Thirty-nine healthy male Wistar rats were randomly divided into 3 groups, normal control(NC) group, CIH group and CIH+Ad group with 13 rats in each. Rats in NC group were kept breathing normal air, while rats in both CIH and CIH+Ad groups experienced the same CIH environment(CIH 8h/day for successive 35 days). Rats in CIH+Ad group were given intravenous Ad supplement at the dosage of 10μg twice a week for successive 5 weeks. Rats in the NC and CIH groups were injected with normal saline as a control. After CIH exposure, the levels of serum Ad and genioglossus contractile properties were compared among different groups. Results: (1)Serum Ad level was significantly lower in CIH group than that in NC group [(1210.32±84.20)ng/ml, (2236.43±117.72)ng/ml, P<0.01]. Serum Ad level in CIH+Ad group[(1843.80±91.11)ng/ml] was significantly higher than that in CIH group but lower than that in NC group(all P<0.01). (2)Twitch tension, time to peak tension, half relaxation time and tetanic tension were significantly lower in CIH group than those in NC group(P<0.01).Those contractile properties were improved in CIH+Ad group (P<0.05). (3)Tetanic fatigue indexes of three groups were decreased more rapidly in the first 20 seconds than those in the following 100 seconds. Tetanic fatigue indexes in NC and CIH+Ad groups were significantly higher than that in CIH group. Conclusions: CIH could lead to hypoadiponectinemia, impaired genioglossus contractile properties and decreased fatigue resistence in rats.Such changes could be partially improved by supplement of adiponectin.

OBJECTIVE Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders. Chronic intermittent hypoxia (CIH) is the primary player in OSAS of the many associated factors. This study was in order to investigate the effects of the Adiponectin (Ad) on left ventricular remodeling induced by CIH. METHODS Forty-five rats were randomly divided into three groups: normal control (NC) group, CIH group and CIH plus Ad supplemented (CIH + Ad) group. After 35 days' CIH exposure, masson analysis was used to detect the left ventricular fibrosis and western blot was used to measure the protein expression of collagen I, collagen III and TGF-β/smad2/3 pathway. Gene analysis by RT-PCR was used to study the MMP2 and TIMP2. RESULTS After CIH exposure, the fibrosis of left ventricular in CIH group was significantly remarkable than that in both NC and CIH + Ad groups (P<0.05), although statistical difference existed between NC and CIH + Ad groups (P<0.05). In addition, the protein expression of collagen I as well as collagen III and the ratio of mRNA levels of MMP2/TIMP2 were the highest in CIH group but the lowest in NC group, with CIH + Ad group in between. There was a significant difference among three groups (all P<0.05). The TGF-β/smad2/3 pathway was activated obviously in CIH group, but less noticeably in CIH + Ad group (P<0.05) with a significant difference in the two groups. CONCLUSIONS The present study showed that Ad could ameliorate the left ventricular remodeling induced by CIH via inhibition of the expression of TGF-β/smad2/3 pathway.

Obstructive sleep apnea syndrome (OSAS) is associated with many cardiovascular disorders such as heart failure, hypertension, atherosclerosis, and arrhythmia and so on. Of the many associated factors, chronic intermittent hypoxia (CIH) in particular is the primary player in OSAS. To assess the effects of CIH on cardiac function secondary to OSAS, we established a model to study the effects of CIH on Wistar rats. Specifically, we examined the possible underlying cellular mechanisms of hypoxic tissue damage and the possible protective role of adiponectin against hypoxic insults. In the first treatment group, rats were exposed to CIH conditions (nadir O2, 5-6%) for 8 hours/day, for 5 weeks. Subsequent CIH-induced cardiac dysfunction was measured by echocardiograph. Compared with the normal control (NC) group, rats in the CIH-exposed group experienced elevated levels of left ventricular end-systolic dimension and left ventricular end-systolic volume and depressed levels of left ventricular ejection fraction and left ventricular fractional shortening (p<0.05). However, when adiponectin (Ad) was added in CIH + Ad group, we saw a rescue in the elevations of the aforementioned left ventricular function (p<0.05). To assess critical cardiac injury, we detected myocardial apoptosis by Terminal deoxynucleotidyl transfer-mediated dUTP nick end-labeling (TUNEL) analysis. It was showed that the apoptosis percentage in CIH group (2.948%) was significantly higher than that in NC group (0.4167%) and CIH + Ad group (1.219%) (p<0.05). Protein expressions of cleaved caspase-3, cleaved caspase-9, and cleaved-caspase-12 validated our TUNEL results (p<0.05). Mechanistically, our results demonstrated that the proteins expressed with endoplasmic reticulum stress and the expression of reactive oxygen species (ROS) were significantly elevated under CIH conditions, whereas Ad supplementation partially decreased them. Overall, our results suggested that Ad augmentation could improve CIH-induced left ventricular dysfunction and associated myocardial apoptosis by inhibition of ROS-dependent ER stress.

The objective of this study was to investigate the effects of chronic intermittent hypoxia (CIH) on genioglossal ultrastructure and mitochondrial function as well as the intervention role of adiponectin (Ad).

BACKGROUND:The genioglossus (GG) is involved in the maintenance of an open airway for effective breathing. Although the pathogenesis of obstructive sleep apnea hypopnea syndrome (OSAHS) was closely associated with GG dysfunction, its causes and possible treatment have not been elucidated. The aim of the study was to investigate the effects of chronic intermittent hypoxia (CIH) on serum adiponectin levels, electromyograph (EMG) activity and ultrastructure of GG, as well as the effect of an adiponectin supplement in anesthetized rats.METHODS:Forty-two healthy male Wistar rats were randomly divided into normal control (A), CIH (B) and adiponectin treatment (C) groups, 14 rats in each group. CIH was performed eight hours per day for five weeks in both groups B and C. Group C received transvenous injection of adiponectin at the dosage of 10 microg per injection, twice a week for five weeks. At the end of the 5th week the GG EMG voltage was measured and compared among the three groups. Transmission electron microscope was used to observe the ultrastructure of the GG.RESULTS:CIH caused significant hypoadiponectinemia, weakened activity of GG EMG at both baseline and hypoxia stimulation, and induced ultrastructural pathological changes, such as, myofibril discontinuities, lysis of myofilament, edema of mitochondria and disruption of cristae, vacuolus and lysis of some mitochondria. Venous supplement of adiponectin improved the above pathological changes resulting from CIH.CONCLUSION:CIH resulted in pathological changes in GG's EMG and ultrastructure, which could be improved by supplement of adiponectin and be associated with hypoadiponectinemia caused by CIH.