[关键词]
[摘要]
目的 研究麝香保心丸对大鼠肝硬化致心肌重构的抑制作用及其机制。方法 随机选取70只SD大鼠,每周给药CCl4橄榄油溶液2次(周1和周4各1次),连续给药8周,制备肝纤维化模型。造模第2周末随机处死10只,取肝组织进行HE染色以观察肝纤维化程度,其余60只模型大鼠随机均分为贝那普利(10 mg/kg)阳性对照组、麝香保心丸(45 mg/kg)组和模型组,造模同时给药,每天1次,连续给药6周。另取10只大鼠作为对照组。造模第8周末,测量各组大鼠血压;检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平;Masson染色法检测肝脏与心肌组织中胶原的量;Western blotting检测基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)蛋白的表达;ELISA法检测心肌组织中羟脯氨酸、I型和III型胶原的量;观察各组大鼠肝功能以及肝脏纤维化病变,分析大鼠左心室心肌肥厚指数(LVHI)。结果 模型组大鼠肝功能不同程度地损害、肝纤维化及心肌损伤。与模型组相比,麝香保心丸组大鼠血清ALT、AST及肝脏胶原的量明显下降(P<0.01),心肌组织中MMP-9、TIMP-1的表达下调,羟脯氨酸、I型和III型胶原、蓝染胶原的量和LVHI均明显降低(P<0.05),MMP-9/TIMP-1值升高(P<0.05)。贝那普利对各项指标也有不同程度的改善作用。结论 麝香保心丸在抗肝纤维化、改善心肌重构方面的疗效与贝那普利无显著差异,其对肝损害的肝保护作用强于贝那普利且对血压无明显影响,整体疗效优于贝那普利。
[Key word]
[Abstract]
Objective To investigate the inhibition of Shexiang Baoxin Pills (SBP) on myocardial remodeling due to the development of hepatic cirrhosis and its mechanism. Methods To induce hepatic fibrosis, 70 rats were administered with CCl4, twice daily for eight weeks. At the end of the week 2, 10 rats were executed, the liver tissues were HE stained to confirm the formation of hepatic fibrosis, and the rest rats were randomly and equally divided into benazepril [positive control, 10 mg/(kg?d)], SBP [45 mg/(kg?d)], and model groups. The rats were ig administered for six weeks. Ten rats from the total of eighty rats were taken as the normal control group. At the end of the week 8, the blood pressure of all rats was measured, the alanine transarninase (ALT) and aspartate aminotransferase (AST) levels in serum were detected, and the collagen contents in liver and myocardial tissues were measured by Masson staining. The expression of matrix metalloproteinases (MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) were detected by Western blotting, the contents of hydroxyproline, type I and type III collagen in myocardial tissue were measured by ELISA. The liver function and hepatic fibrosis of rats in each group were observed, and the left ventricular hypertrophy index (LVHI) was analyzed. Results There were different degrees of liver function damage, liver fibrosis, and myocardial injury in the rats in the model group. Compared with the model group, SBP could obviously reduce the contents of ALT and AST in serum and hepatic collagen (P < 0.01), the expression of myocardial MMP-9 and TIMP-1, the contents of hydroxyproline, type I and type III collagen, blue-stained collagen, and LVHI (P < 0.05). The ratio of MMP-9/TIMP-1 was obviously heightened (P < 0.05). The indexes of rats in the benazepril group were improved at different degrees. Conclusion There is no difference in the effect of anti-hepatic fibrosis and ameliorating myocardium remodeling between SBP and benazepril. SBP has better effect on protecting liver function with damage but has no influence on blood pressure. SBP has better holistic affect on the treatment of cirrhotic cardiomyopathy than benazepril.
[中图分类号]
[基金项目]