Hypothyroidism alone can lead to myocardial fibrosis and result in heart failure, but traditional hormone replacement therapy does not improve the fibrotic situation. Hydrogen sulfide (H2S), a new gas signaling molecule, possesses anti-inflammatory, antioxidant, and anti-fibrotic capabilities. Whether H2S could improve hypothyroidism-induced myocardial fibrosis are not yet studied. In our study, H2S could decrease collagen deposition in the myocardial tissue of rats caused by hypothyroidism. Furthermore, in hypothyroidism-induced rats, we found that H2S could enhance cystathionine-gamma-lyase (CSE), not cystathionine β-synthase (CBS), protein expressions. Finally, we noticed that H2S could elevate autophagy levels and inhibit the transforming growth factor-β1 (TGF-β1) signal transduction pathway. In conclusion, our experiments not only suggest that H2S could alleviate hypothyroidism-induced myocardial fibrosis by activating autophagy and suppressing TGF-β1/SMAD family member 2 (Smad 2) signal transduction pathway, but also show that it can be used as a complementary treatment to conventional hormone therapy.

目的:探讨H型高血压大鼠认知功能下降与海马神经元凋亡的关系.方法:模型组以1％蛋氨酸饮水喂养自发性高血压大鼠构建H型高血压大鼠模型(模型组),同时以普通饮用水喂养同品系正常血压大鼠作为对照组,Y迷宫和新物体识别实验检测大鼠的行为学改变,Tunel染色观察大鼠海马神经元凋亡.结果:模型组大鼠较对照组大鼠的Y迷宫交替正确率及新物体识别分辨指数明显降低,且模型组大鼠海马神经元凋亡指数明显增加,差异均有统计学意义(P<0.05).结论:H型血压大鼠存在认知功能下降,并与海马神经元凋亡增加有关.

10 OBJECTIVE To investigate the roles and underlying mechanism of exogenous H2S (hydrogen sulfide) in attenuating the my11 ocardial fibrosis in diabetic rats. 12 METHODS: A total of 40 SD rats were randomly divided into 4 groups: control group, STZ group, STZ + H2S group and 13 H2S group. To build the DM rat model , the rats in the STZ group and STZ + H2S group were injected streptozotocin (STZ) 14 intraperitoneally, While the rats in the STZ + H2S group and the H2S group received sodium hydrosulfide (NaHS), which pro15 vides exogenous H2S. Eight weeks later, the myocardial tissues of rats were used to detecting the collagen deposition through 16 Masson staining, as well as some protein expressions related to myocardial fibrosis and signaling pathway by Western blotting. 17 RESULTS: Comparing to control group, the collagen deposition of myocardial matrix remarkably increased in the STZ group, 18 and almost all the proteins that are relative to myocardial fibrosis, inflammatory and signaling pathway show an overexpression, 19 except for PPARG and NF-κBp65. When Compared with the STZ group, the collagen deposition was obviously attenuated in 20 STZ + H2S group, as well as the protein expressions above-mentioned, While PPARG was up-regulated. 21 CONCLUSION: The myocardial fibrosis in DM rats can be attenuated effectively by exogenous H2S, and the underlying 22 mechanism is likely to regulating PKC-ERK1/2MAPK signaling pathway, improving the MMPs/TIMPs expression dysregula23 tion and inhibiting inflammatory reaction. 24

目的 观察硫化氢(H2S)对阿霉素诱导的大鼠心肌纤维化及神经调节蛋白(NRG)1和ErbB2(又名HER2,NEU,CD340)蛋白表达的影响.方法 取SD雄性大鼠随机分为4组:对照组,模型组,H2 S模型组,H2 S对照组.经腹腔注射阿霉素建立心肌损伤大鼠模型,对照组和H2 S对照组经腹腔注射同等剂量的生理盐水;建模后,H2 S模型组和H2 S对照组每日经腹腔注射硫氢化钠溶液;Masson染色观察心肌纤维化及计算心肌胶原容积分数(CVF);Western印迹检测NRG1和ErbB2蛋白的表达.结果 与对照组相比,模型组心肌细胞紊乱,心肌纤维沉积明显增多、CVF显著增高(P<0.05),心肌NRG1和ErbB2蛋白的表达明显下降(P<0.05);而与模型组相比,H2S模型组心肌组织纤维沉积明显减少、CVF显著下降(P<0.05),NRG1和ErbB2蛋白的表达显著上调(P<0.05).结论 H2 S可以改善阿霉素导致的心肌纤维化,其发生机制可能与通过NRG1/ErbB2通路上调NRG1和ErbB2蛋白表达有关.

Purpose: This study aimed to figure out the effects of exogenous hydrogen sulfide (H2S) on isoproterenol (ISO)-induced myocardial fibrosis and to verify potential mechanisms of cardiomyocyte apoptosis. Methods: Male Sprague-Dawley rats were randomly assigned into the control group, ISO group, ISO + H2S group, and H2S group. ISO was injected into the abdominal cavities of rats for 7 consecutive days to establish animal models of heart failure. Cardiac collagen deposition and collagen volume fraction (CVF) were measured by Masson's staining. Cardiomyocyte apoptosis was observed by TUNEL staining. Expression of related proteins in CaMKII/NF-kappa B signaling pathways, apoptosis, and MMPs/TIMPs was detected with the method of Western blotting. Expression of apoptosis-related miRNAs was detected through RT-qPCR. Results: Compared to the control group, expression of CaMKII/NF-kappa B, caspase2, and caspase3 proteins, as well as proapoptotic miRNAs, were significantly upregulated in the ISO group, while expression was downregulated in the ISO + H2S group. Expression of Bcl-2 proteins was decreased in the ISO group but increased in the ISO + H2S group. Masson's staining results showed that cardiac collagen deposition and CVF were significantly increased in the ISO group but decreased in the ISO + H2S group. Findings obtained from TUNEL staining indicated that the ratio of TUNEL-positive cell nuclei in the ISO + H2S group was lower than that in the ISO group. Conclusion: The current study highlights that exogenous H2S can inhibit myocardial fibrosis and cardiomyocyte apoptosis in ISO-induced rats. The mechanisms may be associated with downregulation of CaMKII/NF-kappa B signaling pathways and expression of apoptosis-related miRNAs.

OBJECTIVE: To explore the effect of gefitinib-coated balloon suppressive action on the excessive hyperplasia of intima after balloon injury of common carotid artery in rats and on the PI3K/AKT signal pathway.METHODS: MTT method and the expression of Bcl-2 and Caspase-3 proteins were detected in vitro; Adult SD rats were randomly split into 5 groups, namely sham group, model group, low-dosage gefitinib-coated balloon group, high-dosage gefitinibcoated balloon group, and paclitaxel-coated balloon group.The intimal proliferation of arteries, PCNA, P-AKT and PI3K protein expression, the cell apoptosis, expression of MMP9, TGFβ and IL6 mRNA were measured by hematoxylin and eosin (H&E) staining, immunohistochemistry, TUNEL staining, and RT-qPCR.RESULTS: At the same time and concentration, Gefitinib suppressed the proliferation of smooth muscle cell more significantly than paclitaxel.Bcl-2 and Caspase-3 in vascular smooth muscle and endothelial cells (VSMC, EC) were significantly downregulated and up-regulated after the cells were treated with gefitinib and paclitaxel.In gefitinib-and paclitaxel-coated balloon groups, significant up-regulations were found in the area of lumen.Furthermore, the expression of PCNA suggested that all coated balloons could suppress the excessive proliferation of smooth muscle cells in the hyperplastic intima compared with the control group.In gefitinib-and paclitaxel-coated balloon group, the expression of PI3K/AKT was significantly down-regulated.The use of drug-coated balloons mitigated the cell apoptosis in TUNEL.The expressions of MMP9, TGFβ and IL6 mRNA in the model group were obviously up-regulated; and they were obviously down-regulated in the high-dose gefitinib-coated balloon group compared with the model group.CONCLUSIONS: Gefitinib-coated balloons were able to suppress the excessive proliferation in the common carotid arterial intima of rats more effectively than the paclitaxel-coated ones.The underlying mechanism may cover the PI3K/AKT signal pathway.

Objective: The aim of this study was to explore the effects of H2S on myocardial fibrosis induced by hyperthyroxine and expression of STAT signal pathways, miR-21, and miR-29a in the myocardium. Methods: A total of 40 rats were selected and randomly stratified into 4 groups, including the control group (Control), HCM model group (Thy), H2S-intervention model group (Thy+H2S), and H2S-intervention normal group (H2S). Hyperthyroidism rat models were prepared by intraperitoneal injections of L-thyroxine. Rats in the control group received intraperitoneal injections of normal saline. NaHS solution was added to rats in the Thy+H2S group and H2S group. LVs, LVd, LVPWs, and EF values were measured by echocardiography, Pathological changes in myocardial cells and myocardial interstitium were observed by H&E staining. Collagen deposition in the myocardium was also observed by Masson’s staining. Protein expression of STAT1, STAT3, AKT1, TGF-β1, NFKB p65, PI3K, TIMP1, TIMP4, MMP12, MMP13, MMP16, and MMP24 was detected by Western blotting and expression of miR-21 and miR-29a in myocardial tissues was measured by real-time fluorescence quantitative PCR (RT-qPCR). Results: Compared with the control group, rats in the Thy group showed significant decreases in weight and rapid acceleration in heart rates (P<0.05). Findings of pathological examinations revealed that myocardial fibers were in disordered arrangement. Collagen deposition in the myocardium was significantly increased and values of LVs and LVd were significantly increased (P<0.05). Moreover, protein expression of STAT1, STAT3, AKT1, TGF-β1, PI3K, TIMP1, TIMP4, MMP13, and MMP24 in myocardial tissues was significantly upregulated (P<0.05). Expression of MMP12 and MMP16 was significantly downregulated (P<0.05). Comparisons between the Thy group and Thy+H2S group suggested that the weight of rats in Thy+H2S was significantly increased, accompanied by a reduction in heart rates (P<0.05). Also, the pathological examination showed that some improvement was identified in myocardial fibers in disordered arrangement and collagen deposition in the myocardium was significantly reduced. Moreover, values of LVs and LVd were significantly decreased (P<0.05), protein expression of STAT1, STAT3, AKT1, TGF-β1, PI3K, TIMP1, TIMP4, MMP13, and MMP24 was obviously downregulated (P<0.05), and expression of MMP12 and MMP16 was significantly upregulated (P<0.05). Conclusion: H2S can ameliorate myocardial fibrosis induced by hyperthyroxine. Relevant mechanisms might be correlated with regulation of STAT3 signal pathways, downregulation of expression of miR-21, and upregulation of expression of miR-29a.

OBJECTIVE To investigate the roles and underlying mechanism of exogenous H2S (hydrogen sulfide) in attenuating the myocardial fibrosis in diabetic rats.METHODS: A total of 40 SD rats were randomly divided into 4 groups: control group, STZ group, STZ + H2S group and H2S group.To build the DM rat model , the rats in the STZ group and STZ + H2S group were injected streptozotocin (STZ) intraperitoneally, While the rats in the STZ + H2S group and the H2S group received sodium hydrosulfide (NaHS), which provides exogenous H2S.Eight weeks later, the myocardial tissues of rats were used to detecting the collagen deposition through Masson staining, as well as some protein expressions related to myocardial fibrosis and signaling pathway by western blotting.RESULTS: Comparing to control group, the collagen deposition of myocardial matrix remarkably increased in the STZ group, and almost all the proteins that are relative to myocardial fibrosis, inflammatory and signaling pathway show an overexpression, except for PPARG and NF-κBp65.When Compared with the STZ group, the collagen deposition was obviously attenuated in STZ + H2S group, as well as the protein expressions above-mentioned, While PPARG was up-regulated.CONCLUSION: The myocardial fibrosis in DM rats can be attenuated effectively by exogenous H2S, and the underlying mechanism is likely to regulating PKC-ERK1/2MAPK signaling pathway, improving the MMPs/TIMPs expression dysregulation and inhibiting inflammatory reaction.

This study aims to investigate the role and regulatory mechanism of the Hydrogen sulfide (H2S) in amelioration of rat myocardial fibrosis induced by thyroxine through interfering the autophagy via regulating the activity of PI3K/AKT1 signaling pathway and the expression of relative miRNA. 40 adult male SD rats were randomly divided into 4 groups (n = 10): the control group, the thyroxine model group (TH group), the model group with H2S intervention (TH + H2S group) and the normal group with H2S intervention (H2S group). Pathological changes were observed via H&E staining and Masson staining, Expressions of MMPs/TIMPs, PI3K/AKT, autophagy-related proteins in myocardial tissues were detected via Western blotting, and the expressions of miR-21, miR-34a, miR-214 and miR-221 were detected via RT-qPCR. Compared with the control group, in the TH group, myocardial fibrosis was more significant, the expressions of proteins in PI3K/AKT and autophagy-related proteins were significantly decreased, as well as the expression of miR-221; while the expressions of miR-21, miR-34a and miR-214 were significantly elevated. By contrast, all above-mentioned changes were obviously reversed with H2S treatment, which demonstrated the positive function of H2S in amelioration of rat myocardial fibrosis induced by thyroxine. The mechanism of such amelioration may be correlated with autophagy activated by the upregulation of expression of PI3K/AKT signaling pathway and downregulation of expressions of miR-21, miR-34a and miR-214.

目的 探索通心络胶囊对压力超负荷大鼠心肌肥厚和QT离散度以及缝隙连接蛋白43(connexin 43,Cx43)表达的影响.方法 随机均分45只雄性SD大鼠成3组:对照组(control,C),模型组(model,M),治疗组(treat-ment,T),腹主动脉缩窄手术建立压力超负荷大鼠模型,予通心络胶囊[1.5 g/(kg·d)]干预12周后,以多普勒超声心动图检测,同时测定大鼠QT离散度,大鼠处死后取左室心肌组织行HE染色,以免疫组化方法检测Cx43的表达及分布,RT-PCR法检测Cx43 mRNA的表达.结果 M组大鼠心脏多普勒结果与C组比较显示IVSs、VPWs、LIVSd和LVPWd均有增加(均P＜0.01);而T组和M组比较,以上检测参数则得以改善.与C组相比,M组QT离散度明显延长(P＜0.01),与M组相比,T组QT离散度明显缩短(P＜0.01).同时HE染色显示:与C组相比,M组心肌细胞肥大明显(P＜0.01),呈无序排列,T组与M组比较,心肌肥大及排列均较其改善(均P＜0.01).RT-PCR及免疫组化检测结果均显示:与C组相比,M组Cx43 mRNA和蛋白的表达均有明显下调(均P＜0.05),而T组与M组相比,Cx43 mRNA和蛋白的表达有所上调(均P＜0.05).结论 通心络胶囊在改善压力超负荷大鼠心肌肥厚的同时也缩短QT离散度及上调Cx43的表达.

OBJECTIVE To observe the effects of exogenous hydrogen sulfide (H2 S) on myocardial fibrosis induced by high dose thyroxine and the expression of MMPs/TIMPs and STAT3.METHODS Forty male SD rats were divided into four groups by a completely randomized method:control group (Con),hyperthyroidism group (L-Thy),hydrogen sulfide intervention group (L-Thy + H2S) and hydrogen sulfide control group (H2S).A rat model of hyperthyroidism was established by intraperitoneal injection of levothyrocine (L-Thy,10 mL·kg-1 ·d-1).Then,animals in L-Thy + H2S group and H2S group were treated with sodium hydrosulfide solution (1 ml· kg-1 · d-1),animals in Con group and L-Thy group were treated with the same volume of saline.These rats were sacrificed after four weeks,the collagen deposition of left ventricular myocardium was observed by Masson staining,the collagen volume fraction (CVF) was calculated,and the expressions of MMP8,MMP16,TIMP1 and STAT3 proteins were detected by Western-blot.RESULTS Compared with Con group,the L-Thy group showed significantly increased collagen fibers,the CVF also had increased collagen fibers (P＜0.05).Besides,the MMP8,MMP16 and STAT3 showed increased protein expression,while TIMP1 protein expression decreased significantly (P＜0.05).Compared with L-Thy group,the deposition of collagen fibers in H2S + L-Thy group was improved,and CVF decreased (P＜0.05).In addition,the expressions of MMP8,MMP16 and STAT3 proteins decreased,TIMP1 expression obviously increased (P＜0.05).CONCLUSION Hydrogen sulfide may improve the expression disorder of MMPs/TIMPs by downregulating STAT3,thereby improving the high dose thyroxine induced myocardial fibrosis.

Recent studies have indicated the existence of an endogenous sulfur dioxide (SO2)-generating system in the cardiovascular system. The present study aimed to discuss the function and regulatory mechanism of gaseous signal molecule SO2 in inhibiting apoptosis and endoplasmic reticulum stress (ERS) via the Hippo-MST signaling pathway to improve myocardial fibrosis of diabetic rats. A total of 40 male Sprague-Dawley rats were randomly divided into four groups (10 rats per group): Normal control group (control group), diabetic rats group [streptozotocin (STZ) group], SO2 intervention group (STZ+SO2 group) and diabetes mellitus rats treated with L-Aspartic acid ss-hydroxamate (HDX) group (HDX group). Diabetic rats models were established by intra-peritoneal injection of STZ (40 mg/kg) Following model establishment, intra-peritoneal injection of Na2SO3/NaHSO3 solution (0.54 mmol/kg) was administered in the STZ+SO2 group, and HDX solution (25 mg/kg/week) was administered in the HDX group. A total of 4 weeks later, echocardiography was performed to evaluate rats' cardiac function; Masson staining, terminal deoxynucleotidyl transferase dUTP nick end labeling staining and transmission electron microscopy examinations were performed to observe myocardial morphological changes. ELISA was employed to determine the SO2 content. Western blot analysis was performed to detect the expression of proteins associated with apoptosis, ERS and the Hippo-MST signalling pathway. Compared with the control group, the STZ group and HDX group had a disordered arrangement of myocardial cells with apparent myocardial fibrosis, and echocardiography indicated that the cardiac function was lowered, there was an obvious increase of apoptosis in myocardial tissue, the expression levels of apoptosis-associated protein B-cell lymphoma associated protein X, caspase-3 and caspase-9 were upregulated, and Bcl-2 expression was downregulated. The expression of ERS and Hippo-MST pathway-associated proteins, including CHOP, GRP94, MST1 and MST2, were significantly upregulated. By contrast, these above-mentioned changes were reversed by SO2 treatment. Compared with STZ group, the HDX group had a further increase of myocardial fibrosis and apoptosis, while there were no statistically significant differences in the expression of Bax/Bcl-2, caspase-3, caspase-9 and ERS and Hippo-MST pathway-associated proteins. The results of the present study demonstrated that the gaseous signal molecule SO2 can effectively improve the myocardial fibrosis of diabetic rats, and its mechanism may be associated with reduced apoptosis and ERS by downregulated Hippo-MST pathway.

Objective To observe the effects of Hydrogen sulfide ( H2 S) on myocardial fibrosis in rat models of hyperthyroidism in-duced by high thyroid hormone. Methods The hyperthyroidism in rats were induced by intraperitoneal injection of the L-Thyroxine solution (250 μg/ml,10 ml·kg-1 ·d-1 ) for 28 days. Sodium hydrosulfide was taken as the exogenous donor of hydrogen sulfide. 40 male SD mice were randomly divided into control, model, intervention of H2S(L-Thyroxine+H2S group)and control of H2S(H2S group)groups. All the mice were killed after 4 weeks, then Masson staining was performed to observe the myocardial fibrosis and the collagen volume fraction (CVF) was measured, the expression of MMP-11, MMP-16 and PKCα was detected by Western blot. Results Compared with control group, the myocardial fibrosis and CVF were obviously increased in the L-Thyroxine group (P<0. 05). Compared with L-Thyroxine group, the myocardial fibrosis and CVF were significantly decreased in L-Thyroxine+H2S group (P<0. 05), and there was no difference between control and H2S groups (P>0. 05). Compared to control group, the expression of MMP-11 and MMP-16 were up-regulated in L-Thyroxine group (P<0. 05), while the expression of above target proteins were down-regulated obviously in L-Thyroxine+H2S group (P<0. 05), there was still no difference between control group and H2S group (P>0. 05). Also, the expression of PKCα was similar in each group (P>0. 05). Conclusions The H2S may improve the rats myocardial fibrosis of hyperthyroidism induced by thyroid hormone through regulating the expression of protein of MMP-11, MMP-16 but has nothing to do with the pathway of PKCα.

Myocardial fibrosis is one of the most important pathological features of alcoholic cardiomyopathy (ACM). Hydrogen sulfide (H2S) exerts protective effects in various types of cardiovascular disease, which has been demonstrated by many previous studies. However, there is a lack of adequate research on the effect of H2S on myocardial fibrosis in ACM. The present study aimed to investigate the etiopathogenic role of H2S in myocardial fibrosis induced by chronic alcohol intake. An ACM mouse model was induced by consumption of 4% ethanol solution in drinking water for 12 weeks. Sodium hydrosulfide (NaHS) was used as a donor to provide exogenous H2S. Twelve weeks later, mice were sacrificed to calculate the heart to body weight ratio. The degree of myocardial collagen deposition was evaluated by Masson's and Van Gieson's staining, the expression level of collagen. was measured by immunohistochemistry and autophagosomes were observed by transmission electron microscopy. In addition, the expression levels of autophagy-associated proteins and fibrosis-associated proteins were detected by western blotting, and the expression levels of miR-21 and miR-211 were detected by reverse transcription-quantitative polymerase chain reaction. The outcomes of the study revealed that chronic alcohol intake results in myocardial fibrosis, enhanced myocardial collagen deposition and increased expression levels of collagen I, autophagy, autophagy-associated proteins (Beclin 1, Atg3 and Atg7) and fibrosis-associated proteins (MMP8, MMP13, MMP14, MMP17 and TGF-beta 1), as well as miR-21 and miR-221. These results were markedly reversed following treatment with H2S. The present study confirmed that H2S relieves myocardial fibrosis in mice with ACM, and the underlying mechanism may involve the downregulation of autophagy and miR-21 and miR-211 expression levels.

Objective:To observe the effect of hydrogen sulfide on myocardial fibrosis and matrix metalloproteinase 14 (MMP14),matrix metalloproteinase 16 (MMP16) and activating transcription factor 1 (STAT1) expression in hyperthyroid cardiomyopathy rat.Method:SD male rats were randomly divided into 4 groups:control group (C),hyperthyroid group (L-Thy),hydrogen sulfide+ hyperthyroid group (H2 S+ L-Thy),hydrogen sulfide intervention group (H2S).Masson staining was used to observe myocardial fibrosis and calculate myocardial collagen volume fraction;the expression of MMP16,MMP14 and STAT1 protein were detected by western blotting.Result:compared with C group,the myocardial cell disorder in rats with hyperthyroid cardiomyopathy.Myocardial fiber deposition increased,CVF increased(P＜0.05),expression of myocardial MMP14,MMP16 and STAT1 protein were increased (P＜0.05) in L-Thy group;Compared with L-Thy group,H2S+L-Thy group myocardial cell disorder improved,CVF decreased (P＜0.05),MMP14,MMP16 and STAT1 expression decreased (P＜0.05).Conclusion:Hydrogen sulfide may down regulate the expression of MMP14 and MMP16 through the STAT1 pathway,and improve the myocardial fibrosis induced by thyroxine in rats.

Objective To observe the effects of Wenxin Granules on cardiac hypertrophy and QT dispersion and the ex pression of connexin43 (Cx43) in pressure-overloaded rats.Methods Forty-five male Sprague-Dawley rats were divided into normal group (group N),hypertrophy group (group H) and Wenxin Granules group (group W) by completely randomized method.The rat model of cardiac hypertrophy was established by constriction of abdominal aorta.When treated with Wenxin Granules 6.25 g/(kg·d) for 12 weeks,these rats were detected by echocardiography and QT dispersion.The pathological morphology of ventricle tissue was observed by HE staining,the expression of Cx43 protein and Cx43 mRNA in left ventricle was respectively detected by immunohistochemistry and RT-PCR after rats were sacrificed.Results The rat model of cardiac hypertrophy induced by pressure overload was established.Compared with group N,the rats in group H had obvious hypertrophy.Compared with group H,the above parameters were improved in group W.In addition,the QT dispersion of group H was significantly higher than that of group N,and the QT dispersion of group W was lower than that of group H.Meanwhile,compared with group N,group H showed hypertrophy and disorder of cardiac muscle cell,and the expression of Cx43 protein and mRNA in left ventriole myocardium was significantly decreased;while the hypertrophy and disorder were improved in group W when compared with group H,Cx43 protein and mRNA expression was also significantly increased.Conclusion Wenxin Granules can improve cardiac hypertrophy in pressureoverloaded rats,decrease QT dispersion and improve the remodeling of Cx43 in myocardium.

Objective To investigate the effects of recombinant human brain natriuretic peptide (rhBNP) on the myocardial remodeling and connexin 43 (Cx43) expression of rats with cardiac failure caused by pressure overload.Methods Forty-five male SD rats were randomly divided into the heart failure group (group F), heart failure+rhBNP group (group B), and sham operation group (group SO) with 15 rats in each group.In the group F and group B, we established the rat models of pressure overload-induced heart failure by abdominal aortic constriction, while in the SO group, rats did not receive coarctation of the abdominal aorta.Rats in the group B were subcutaneously injected with rhBNP (25 ug/kg/d), while rats in the group SO and group F were injected intraperitoneally with normal saline for 8 weeks.The left ventricular function, hemodynamics, QT dispersion, left ventricular myocardial pathology, myocardial fibrosis and collagen deposition, and myocardial Cx43 protein expression were detected in each group.Results Compared with the SO group, the left ventricular function, hemodynamics, QT dispersion, left ventricular myocardial histopathology, myocardial fibrosis deposition, myocardial Cx43 protein expression were statistically significant in the group F (all P<0.05), which showed that heart failure model was established successfully.Compared with group F, the heart function of rats increased, the mean arterial pressure and QT dispersion decreased, the disordered arrangement of myocardial cells reduced, collagen deposition decreased between cardiac myocytes, and the expression of Cx43 increased in the group B (all P<0.05).Conclusion rhBNP can improve the cardiac function and hemodynamic indexes in rats with heart failure under pressure overload, up-regulate the myocardial expression of Cx43 protein, and inhibit myocardial remodeling.

OBJECTIVE:To observe the effects of Shexiang Baoxin Pill (SBP) on isoprenaline (Iso)-induced changes in myocardial cell volume, shape, and connexin 43 (Cx43) expression.
 Methods: H9C2 myocardial cells were randomly divided into a control group, a Iso group and a Iso+SBP group. After 72 h of culture, the average surface area of H9C2 cells was measured under phase contrast microscope. Bicinchoninic acid (BCA) protein assay was carried out to determine the concentration of proteins. The survival rate of myocardial cells was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay, and the Cx43 expression was detected by Western blot.
 Results: The mean surface area and Cx43 concentration in Iso-treated myocardial cells were increased under the phase contrast microscope (P<0.05). Compared with the Iso group, the mean surface area was decreased, and the Cx43 concentration was reduced in the Iso+SBP group (both P<0.05). Compared with the control group, the Cx43 expression was obviously down-regulated in the H9C2 cells of the Iso group (P<0.05); while compared with the Iso group, the Cx43 expression was obviously up-regulated in the Iso+SBP group (P<0.05).
 Conclusion: Shexiang Baoxin Pills can prevent Iso-induced myocardial hypertrophy and down-regulate Cx43 expression.