Background Cardiac dysfunction caused by sepsis is a serious challenge for ICU doctors. Previous studies showed that the beta adrenergic receptor (β- AR) signaling pathway system can cause abnormal heart function. Studies have also shown that esmolol, a type of beta blocker, participates in the beta receptor desensitization that occurs. This study intends to further explore the specific mechanism of esmolol in the protection of cardiac function.Method In this study, rats were randomly divided into three groups: Sham (sham operation group), CLP (cecal ligations and function group) and ES (esmolol group). The three groups were divided into two subgroups: A and B. Group A was used to observe the number of survival days. Group B was divided into 6 hours,12 hours and 24 hours according to the time after the operation to take samples, and the rats were sacrificed after the corresponding intervention. The inflammatory factors and the factor of β receptor pathway were measured by different methods. And the hypothesis was verified by statistical methods.Results ELISA tests demonstrated that the levels of inflammatory factors CA,TNF-α, and IL-6, as well as G protein pathway factors AC, CAMP and PKA in the CLP group were significantly higher than those in the Sham group, while those factors in the ES group were significantly lower than those in the CLP group, cardiac function factor cTnI is the opposite. Western blotting showed that, compared with the CLP group, the inflammatory proteins MYD88 and NF-KB in the myocardial tissue of the ES group were significantly decreased, while the levels of the beta receptor pathway proteins β1-AR, β2-AR, β-arrestin-1 and β-arrestin-2 were significantly increased, and the result of β-ARK was the opposite. Pathological results and immunofluorescence results indicated that the degree of myocardial cell injury in the ES group was significantly improved compared with that in the CLP group.Conclusion Esmolol has a protective effect on the heart by selectively preventing the pathologic signaling pathway mediated by overactivation of beta receptors while retaining the normal signaling pathway.

Cardiovascular disease is the main cause of mortality and morbidity in the world, especially in developing countries. Drug therapy is one of the main ways to treat cardiovascular diseases. Among them, great progress has been made in the treatment of cardiovascular diseases with traditional Chinese medicine. In terms of experimental research, the mechanism of traditional Chinese medicine in the treatment of cardiovascular diseases has been thoroughly discussed in vitro and in vivo. In terms of clinical treatment, traditional Chinese medicine with flavonoids, saponins and alkaloids as the main effective components has a definite effect on the treatment of cardiovascular diseases such as arrhythmia, myocardial ischemia, angina pectoris and myocardial infarction, with high safety and good application prospects. With the further research on the effective ingredients, mechanism and adverse reactions of traditional Chinese medicine, it will be beneficial to the effectiveness of traditional Chinese medicine, reduce side effects and promote the modernization of traditional Chinese medicine. Calycosin and its derivatives, the main bioactive flavonoids in Astragalus membranaceus have multiple biological effects, such as antioxidant, pro-angiogenesis, anti-tumour, and anti-inflammatory effects. Based on the above biological effects, calycosin has been shown to have good potential for cardiovascular protection. The potent antioxidant effect of calycosin may play an important role in the cardiovascular protective potential. For injured cardiac myocytes, calycosin and its derivatives can alleviate the cell damage mainly marked by the release of myocardial enzymes and reduce the death level of cardiac myocytes mainly characterized by apoptosis through various mechanisms. For vascular endothelial cells, calycosin also has multiple effects and multiple mechanisms, such as promoting vascular endothelial cell proliferation, exerting vasodilating effect and directly affecting the synthesis function of endothelial cells. The present review will address the bioactivity of calycosin in cardiovascular diseases such as protective effects on cardiac myocytes and vascular endothelial cells and elucidate main mechanism of calycosin and its derivatives to exert the above biological effects.

In order to study the effects of acrylonitrile (ACN)-induced oxidative damage on endoplasmic reticulum stress (ERS) signaling pathways in rat liver, 50 healthy adult male SD rats were randomly divided into 5 groups, 10 rats in each group, according to the body weight. The rats' groups were treated with 0, 12.5, 25, 50.0 mg·kg-1 ACN via gavage, respectively. NAC group were treated by intragastric administration of 300.0 mg·kg-1 NAC after 30 min of reperfusion 50.0 mg·kg-1 ACN, 1 time per day, 6 days per week for 13 weeks. The levels of GSH and MDA, the activity of SOD, GSH-Px, CAT in liver tissue were measured by spectrophotometry method. The mRNA and protein expressing levels of ERS-related GRP78, CHOP and caspase-12 were detected by RT-PCR and West-ern Blot. The results showed that the levels of GSH in low and middle ACN group were significantly decreased compared to control group. The activity of GSH-Px and SOD, the levels of MDA in low dose group was signifi-cantly increased compared to control group. CAT activity in middle and high dose groups were significantly de-creased in comparison with the control group. Compared with high ACN group, GSH levels was significantly in-creased in NAC intervention group, and also MDA levels and SOD activity were significantly decreased. GRP78, CHOP and caspase-12 in high ACN group showed significant higher mRNA levels than that in the control group. The expression of CHOP and caspase-12 mRNA in NAC group were significantly lower than that in high ACN group. Western Blot showed that the expression levels of GRP78, CHOP and caspase-12 protein in high ACN group were significantly higher than that in control group. The expression levels of GRP78, CHOP, and caspase-12 protein in NAC group were lower than that in high ACN group. Our study indicated that exposure to ACN could induce oxidative damage on rats' liver, and then activate ERS signaling pathway. NAC could reduce the degree of oxidative damage and antagonize the ERS signaling pathway. Further study is needed to find the mechanism of this oxidative damage inducted by ACN on ERS signaling pathway.

Oleuropein, the main glycoside present in olives, has been reported to have cardioprotective effect, but the exact mechanism has not been clearly elucidated. This study attempted to clarify the cardioprotective effect of oleuropein against simulated ischemia/reperfusion- (SI/R-) induced cardiomyocyte injury in vitro and further explore the underlying mechanism. Here we confirmed that oleuropein reduced the cell injury in neonatal rat cardiomyocyte induced by SI/R evidenced by decreasing MTT dye reduction and LDH activity in the culture medium. Meanwhile, the compound also inhibited reactive oxygen species excessive generation and stabilized mitochondrial membrane potential after SI/R. The flow cytometry assessment results indicated the inhibition of cellular apoptosis with oleuropein treatment. Furthermore, western blot analysis showed that oleuropein attenuated the expression of Cyt-C, c-caspase-3, and c-caspase-9, increased the Bcl-2/Bax ratio, and enhanced the phosphorylation of ERK1/2 and Akt after SI/R. However, the phosphorylation enhancement was partially abolished in the presence of LY294002 (PI3K inhibitor) and U0126 (ERK inhibitor). All these findings indicate that oleuropein has the protective potential against SI/R-induced injury and its protective effect may be partly due to the attenuation of apoptosis via the activation of the PI3K/Akt and ERK1/2 signaling pathways.

Objective To explore the effect of acrylonitrile induced oxidative stress on flagella ultrastructure and sperm quality of rat epididymis.Methods According to the body weight,40 adult specific pathogen free Sprague-Dawley male rats were randomly divided into one control group and three exposed groups (each group of 10).Rats in exposed group were treated with ACN at dose of 12.5,25 and 50 mg/kg respectively once a day for thirteen weeks via gavage.The reactive oxygen species (ROS),methane dicarboxylic aldehyde (MDA),superoxide dismutase(SOD) and mitochondrial membrane potential(MMP) levels in sperm and the quality of sperm were tested.and the ultrastructure of sperm flagella was observed.Result Sperm MMP in 50 mg/kg group was significantly lower than that in the control group and other groups (1.34 ± 0.10)(P ＜ 0.05).The concentration of ROS in 50 mg/kg group was significantly higher than that in the control group and other groups (P ＜ 0.05).SOD activity in treatment groups were statistically significant compared with the control group (P ＜ 0.05).Under the transmission electron microscopy,the outer dense fiber and mitochondria in sperm tails were damaged in 25 and 50 mg/kg groups.Sperm density in 50 mg/kg group was (3.52 ± 0.46) × 106/ml significantly decreased compared with the control group,12.5 mg/kg group and 25 mg/kg group [respectively (5.71 ±0.66) × 106/ml,(4.95 ± 1.33) × 106/ml and (5.99 ± 0.78) × 106/ml] (P ＜ 0.05).Sperm motility rate in 50 and 12.5 mg/kg group was respectively (62.18 ± 3.4) ％ and (66.25 ± 7.23) ％,and the difference had statistically significant compared with the control group (27.77 ± 4.85) ％ (P ＜ 0.05).The rate of "d" grade sperm in 50 and 25 mg/kg group were respectively (40.76 ± 1.47)％ and (37.77 ±3.41)％,that were significantly increased compared with the control group (27.77 ±4.85)％ and 12.5 mg/ kg group(31.77 ±4.85)％ (P ＜0.05).The average path velocity in control group was (18.17 ± 2.24) μm/s,and was significantly higher than it in each treated group (P ＜0.05).Straight-line speed of sperm in 50 mg/kg group was significantly decreased compared with the control group (P ＜ 0.05).ROS concentration and sperm MMP was significantly negatively correlated (r =-0.643,P =0.024).ROS concentration was showed a significant negative correlation with SOD activity (r =-0.713,P =0.009).Sperm activity was showed a significant negative correlation with ROS concentration (r =-0.629,P =0.028).The average path velocity was showed a significant negative correlation with ROS concentration (r =-0.839,P =0.001).The rate of "d" grade sperm was showed a significant positive correlation with ROS concentration (r =0.699,P =0.011).Conclusion ACN could induce increasing ROS levels in sperm,damage the outer dense fiber and mitochondria in sperm tail.These may be the reasons that ACN could decrease the sperm motility,viability and movement speed.

Acrylonitrile (ACN) treatment can induce testicular toxicity in Sprague-Dawley (SD) rats, with the toxicity potentially related to apoptosis, mediated by nuclear factor-κB (NF-κB). The present study investigated the potential role of NF-κB in the induction of apoptosis and testicular toxicity in ACN-treated rats. Adult male SD rats were randomly divided into 3 treatment groups: a control group (corn oil), an ACN group (50 mg/kg) in which ACN was administered by gavage, and an ACN and N-acetylcysteine (ACN+NAC) group. The rats were given NAC (300 mg/kg) 30 min prior to the administration of ACN, and ACN was administered by gavage for 90 days. The ACN treatment markedly increased malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity in the testis. Glutathione (GSH) was significantly depleted in the ACN groups, and the effects of ACN were blocked by the anti-oxidant NAC. The ACN treatment also increased the expression of NF-κB (p65) and phosphorylated-IκB kinase (IKK)-α/β and decreased the expression of an inhibitor of NF-κB (IκB-α). The pretreatment with NAC significantly inhibited the activation of NF-κB. In addition, the expression of Bax increased after the ACN treatment, and the induction of Bax was abolished by NAC. Taken together, the data suggested that ACN-induced oxidative stress activated the NF-κB signaling pathway, which modulated the expression of Bax and contributed to testicular apoptosis.

This study aimed to investigate the protective effects of apigenin (AP), a flavonoid found in plants, against acrylonitrile (ACN)-induced subchronic sperm and testes injury in rats. Male Sprague-Dawley rats were randomly divided into four groups: a control group (corn oil), an ACN group (ACN 50 mg kg-1), an ACN + AP1 group (ACN + AP 234 mg kg-1), and an ACN + AP2 group (ACN + AP 468 mg kg-1). The ACN + AP group received AP by gavage after treatment with 50 mg kg-1 ACN for 30 min, whereas the rats in the control group were given an equivalent volume of corn oil. The gavage was conducted 6 days per week for 12 weeks. The results showed that AP increased the sperm concentration, motility, and mitochondrial membrane potential (MMP) (P < 0.05), which were reduced by ACN. Conversely, reactive oxygen species (ROS) and malondialdehyde (MDA) were significantly decreased by AP (P < 0.05). AP improved the damage of the ultrastructure of sperm caused by ACN. AP reduced the pathological injuries and spermatogenic cell apoptosis caused by ACN in rat testes. AP also increased glutathione peroxidase activity and decreased MDA content. In conclusion, AP reduces ACN-induced decreasing sperm quality by inhibition of inflammation and oxidative stress.

目的 探讨丙烯腈亚慢性染毒诱导大鼠外周血淋巴细胞DNA的损伤和氧化应激作用.方法 将50只SPF级SD成年雄性大鼠按体重随机分为对照组(玉米油),丙烯腈12.5、25、50 mg/kg组和N-乙酰半胱氨酸组(50 mg/kg丙烯腈+300 mg/kg N-乙酰半胱氨酸),灌胃染毒,1次/d,6d/周,连续13周,末次染毒后处死动物,检测外周血淋巴细胞DNA损伤情况及细胞内活性氧水平、血清8-羟基脱氧鸟苷(8-OHDG)及丙二醛含量.结果 丙烯腈25 mg/kg组大鼠外周血淋巴细胞尾部DNA含量及尾长与对照组比较显著增加(P＜0.05).丙烯腈25 mg/kg组和50 mg/kg组大鼠血清8-OHDG含量与对照组比较差异无统计学意义(P＞0.05).丙烯腈25 mg/kg组和50 mg/kg组大鼠外周血淋巴细胞活性氧水平与对照组比较差异均无统计学意义(P＞0.05).各剂量丙烯腈组大鼠血清丙二醛含量与对照组比较差异均无统计学意义(P＞0.05).N-乙酰半胱氨酸组大鼠血清8-OHDG含量与丙烯腈50 mg/kg组比较降低,差异有统计学意义(P＜0.05).N-乙酰半胱氨酸组大鼠外周血淋巴细胞活性氧水平及血清丙二醛含量与丙烯腈50 mg/kg组比较均降低(P＜0.05).结论 丙烯腈亚慢性染毒对雄性大鼠淋巴细胞DNA有损伤作用,在本实验条件下尚不能证明其DNA损伤由氧化应激导致.

为探索丙烯腈(acrylonitrile,ACN)诱导的氧化应激对大鼠睾丸NF-κB信号通路的影响,将50只SPF级健康SD雄性大鼠按体重随机分为12.5、25、50 mg·kg-1 ACN染毒组,50 mg·kg-1 ACN+300 mg·kg-1 N-乙酰半胱氨酸(N-acetyleysteine,NAC)干预组(NAC干预组),对照组(给予等体积玉米油),每组10只,灌胃,1次/天,6天/周,共90 d.可见光分光光度法检测睾丸组织中超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、还原型谷胱甘肽/氧化型谷胱甘肽比值(glutathione/oxidized glutathione,GSH/GSSG)、丙二醛(malondialdehyde,MDA).免疫荧光染色法检测睾丸核因子-κB(nuclear factor κB,NF-κB)激活及核转移.Western Blot检测睾丸p65、IκB蛋白表达.结果显示,低、高剂量染毒组大鼠睾丸GSH/GSSG比值、GSH-Px酶活性与对照组比较降低(P,＜0.05).中、高剂量染毒组大鼠睾丸MDA含量与对照组比较升高(P,＜0.05).NAC干预组大鼠睾丸MDA含量与高ACN组比较降低(P＜0.05);NAC干预组大鼠睾丸GSH/GSSG比值与高ACN组比较升高(P＜0.05);免疫荧光结果显示,高ACN组大鼠睾丸NF-κB被激活,并转移入细胞核.NAC干预组与高ACN组比较p65蛋白表达及核转移显著减少.Western Blot结果显示,高剂量染毒组大鼠睾丸p65蛋白表达与对照组比较升高(P＜0.05),IκB蛋白表达与对照组比较降低(P＜0.05);NAC干预组大鼠睾丸p65蛋白表达与高ACN组比较降低,IκB蛋白表达与高ACN组比较升高,差异有统计学意义(P＜0.05).结果表明丙烯腈引起的氧化应激激活了大鼠睾丸生殖细胞NF-κB信号通路.

OBJECTIVE Acute lung injury (ALI) is a severe complication for patients undergoing cardiac surgery necessitating cardio-pulmonary bypass (CPB), however, the possible relationship between microRNAs change and ALI induced by CPB is still not completely understood. OBJECTIVE the aim of this study is to determine the microRNAs level changes in patients with ALI induced by CPB and its involved mechanism. METHODS We collected blood samples from 45 patients and performed microRNA microarray experiments to determine the microRNAs level changes in patients with ALI induced by CPB then the result was verified by quantitative real-time PCR (qRT-PCR). Plasma TNF-α level and respiration parameters including respiration index (RI) and oxygenation index (OI) were measured at five different time points before or after CPB. Meanwhile the correlationship between significantly changed microRNAs and TNF-α level and respiration parameters was analyzed. Further more, we transfected miR-320 mimic and inhibitor into A549 cells and observed the proliferation inhibition and apoptosis change caused by oxygen-glucose deprivation/reperfusion. Finally we using dual-luciferase reporter assay, qRT-PCR and western blot investigated the potential target of miR-320. RESULTS The level of miR-320 was higher in CPB caused ALI with the most significance. Correlation analysis found that the level of miR-320 was positively associated with TNF-α and RI (r = 0.649 and 0.564, P < 0.05), but negative correlated with OI (r = -0.638, P < 0.05). In A549 cells, up-regulated miR-320 induced proliferation inhibition and more apoptosis. SIRT1 may be a target of miR-320 and higher miR-320 resulted in lower expression of SIRT both in mRNA and protein level. CONCLUSION miR-320 may mediate the ALI after CPB in which alveolar epithelial cells are injured via down-regulating SIRT1.