摘要
目的研究黄芪甲苷对慢性心力衰竭(CHF)大鼠心肌纤维化和转化生长因子β1(TGFβ1)表达的影响。方法采用腹主动脉缩窄法制作CHF模型,并分为空白组、黄芪甲苷低、中、高剂量(20、40、60 mg/kg)组、缬沙坦(10 mg/kg)组,同时设立假手术组做对照,每日给药(灌胃)1次,持续4周。4周后行血流动力学指标的检测,处死大鼠后计算心脏重量/体质量比(HW/BW)、左心室重量/体质量比(LVW/BW),常规行苏木素-伊红染色观察心肌组织形态学变化,Masson染色观察心肌纤维化,测量胶原容积分数(CVF),RT-PCR、免疫组织化学和蛋白免疫印迹法检测TGFβ1 mRNA以及TGFβ1分子表达水平。结果同空白组相比,黄芪甲苷低、中、高剂量组HW/BW、LVW/BW、CVF、TGFβ1 mRNA、TGFβ1等表达明显减弱(P<0.05),黄芪甲苷中、高剂量组左心室舒张末压、左心室收缩压显著下降,±dp/dtmax显著上升(P<0.05),细胞形态明显改善。结论黄芪甲苷能够抑制CHF大鼠的心肌纤维化,具体作用机制可能是通过抑制心肌组织中TGFβ1的过度表达来实现的。
Objective To observe the effects of astragaloside Ⅳ on myocardial fibrosis and expression of myocardial transforming growth factor （TGFβ1） in rats with chronic heart failure （CHF）. Methods The rat model of CHF was induced by abdominal aorta constriction. Experiments were carried out in the following groups： sham operation group, blank group, astragaloside Ⅳ low, medium and high dose group （20, 40, 60 mg/kg）, valsartan group （10 mg/kg）. The rats in those groups were daily administrated with corresponding drugs for 4 weeks, and then hemodynamic indexes were monitored. After the rats were executed, HW/BW and LVW/BW were measured. Further, conventional HE staining was performed to observe the morphologic changes of myocardial tissue; Masson staining was used to observe myocardial fibrosis and measure collagen volume fraction ; and RT-PCR, immunohistochemistry and Western-blotting were used to monitor the expression level of TGFβ1 mRNA and TGFβ1. Results Compared with the blank group, HW/BW, LVW/BW, collagen volume fraction （CVF） and the expression level of TGFβ1 mRNA and TGFβ1 were obviously reduced in astragaloside Ⅳ low, medium and high dose group （ P 〈 0. 05 ） , and in astragaloside IV medium and high dose group left ventricular end-diastolic pressure and left ventricular systolic pressure were dramatically reduced with dramatically increased ＋ dp/dtmax （P 〈 0. 05） and obviously improved cytology morphology. Conclusions Astragaloside Ⅳ can inhibit myocardial fibrosis in rats with CHF through a possible mechanism involving the inhibition of myocardial TGFβ1 expression by astragaloside Ⅳ.
出处
《新医学》
2016年第1期27-33,共7页
Journal of New Medicine
基金
山东省中医药科学技术研究项目(2013-235)
山东省高校优秀科研创新团队计划资助
关键词
黄芪甲苷
慢性心衰
转化生长因子Β1
心肌纤维化
Astragaloside Ⅳ
Chronic heart failure
Transforming growth factor β1
Myocardial fibrosis
作者简介
通讯作者，张金国，E—mail：cck112000@aliyun．com
