【摘要】 目的:研究黄芪甲苷对腹主动脉缩窄术致慢性心力衰竭(CHF)大鼠心肌纤维化和结缔组织生长因子(CTGF)表达的影响。方法:SD雄性大鼠100只,采用腹主动脉缩窄术建立CHF模型,实验分为假手术组(n=10)、模型组(n=12)和黄芪甲苷低、中、高3个剂量组(20、40、60 mg/kg,n=12),每日灌胃给药1次,连续4周。4周后监测血液动力学指标,处死大鼠后计算左心质量指数(LVMI),常规行苏木素伊红(HE)染色法观察心肌组织形态学变化,Masson染色观察心肌纤维化程度,测量心肌胶原容积分数(CVF),逆转录聚合酶链式反应(RT-PCR)、免疫组化和蛋白免疫印迹(Western-blot)检测CTGF m RNA以及CTGF分子表达水平。结果:同模型组相比:黄芪甲苷低、中、高剂量组LVMI水平减弱;CVF减弱;黄芪甲苷中、高剂量组的左心室舒展末期压力下降、左心室收缩压下降,左心室内压最大变化速率上升,差异均有统计学意义(P<0.05~0.01)。病理形态学明显改善。同假手术组的CTGF平均积分吸光度值(0.09±0.03)、心肌组织CTGF因子表达水平(0.15±0.02)相比,模型组的(0.45±0.04)、(0.57±0.06)均增加;同模型组相比,黄芪甲苷低、中、高剂量组CTGF的平均积分吸光度值(0.39±0.05、0.30±0.06、0.24±0.04)和心肌组织CTGF因子表达水平(0.44±0.05、0.35±0.02、0.28±0.03)均降低,差异均有显著统计学意义(P<0.01)。结论 :黄芪甲苷能够抑制CHF大鼠的心肌纤维化和改善心功能,具体作用机制可能是通过抑制心肌组织中CTGF的过度表达来实现的。更多还原

【Abstract】 Objective: To observe the effects of astragaloside IV on myocardial fibrosis and connective tissue growth factor(CTGF) expression in experimental rats with chronic heart failure(CHF).Methods: CHF model was established by abdominal aorta constriction(AAC) and the rats were divided into 5 groups: Sham operation group, the rats received normal saline 2 ml/day, n=10, CHF group, the rats received normal saline 2 ml/day, n=12; Astragaloside IV groups, CHF rats received astragaloside IV at(20, 40, 60) mg/kg respectively and n=12 in each group. All animals were treated for 4 weeks. Hemodynamic indexes were monitored, left ventricular mass index(LVMI) was calculated, morphologic changes of myocardial tissue was observed by HE staining, myocardial fibrosis degree and collagen volume fraction(CVF) were measured by Masson staining. The mR NA and protein expressions of CTGF were detected by RT-PCR and immunohistochemistry, Western-blot analysis respectivety.Results: Compared with CHF group, 3 Astragaloside IV groups had decreased LVMI and CVF, P<0.05-0.01; Astragaloside IV(40 and 60) mg/kg groups presented decreased LVEDP and LVSP, increased ±dp/dtmax, P<0.01 to P<0.05 and improved pathologicalmorphology. Compared with Sham group, CHF group had increased average CTGF OD value(0.09 ± 0.03) vs(0.45 ± 0.04) and increased expression of myocardial CTGF(0.57 ± 0.06); compared with CHF group, the average CTGF OD values in Astragaloside IV(20, 40, 60) mg/kg groups were all decreased(0.39 ± 0.05),(0.30 ± 0.06),(0.24 ± 0.04) and decreased expressions of myocardial CTGF(0.44 ± 0.05),(0.35 ± 0.02),(0.28 ± 0.03) respectively, all P<0.01.Conclusion: Astragaloside IV can inhibit myocardial fibrosis and improve cardiac function in CHF rats, which might be via inhibiting the over expression of myocardial CTGF.更多还原