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目的研究麝香保心丸对肝硬化致心肌重构的抑制作用及其机制。方法以sc体积分数40%CCl4橄榄油溶液3mL/kg,每周2次,共8周的方法制备大鼠肝纤维化模型,第2周末随机取5只大鼠肝组织作HE染色,观察肝纤维化程度,造模大鼠分别ig麝香保心丸22.5、45 mg/kg,共给药6周,第8周末分别取各组大鼠肝组织、左室心肌组织行组织病理学及透射电镜观察,观察各组大鼠肝脏、心肌组织病理及心肌组织超微结构改变;以RT-PCR和免疫组化染色分析心肌组织中c-fos和c-jun mRNA以及结缔组织生长因子(CTGF)、I型和III型胶原的表达变化。结果造模大鼠均存在不同程度的肝纤维化及心肌损伤。与模型组比较,低剂量麝香保心丸组大鼠肝纤维化程度无明显差异(P>0.05),但心肌损伤程度减轻,心肌组织中c-fos mRNA、c-jun mRNA、CTGF、I型和III型胶原表达明显降低(P<0.05、0.01)。高剂量麝香保心丸组大鼠肝纤维化及心肌损伤程度较低剂量组减轻(P<0.05),心肌组织中c-fos mRNA、c-jun mRNA、CTGF、I型和III型胶原表达均低于低剂量组(P<0.05、0.01)。结论肝硬化大鼠心肌组织心肌即早基因活化、诱导CTGF过度表达而致心肌重构,麝香保心丸可通过抑制心肌即早基因表达,降低心肌CTGF水平而发挥心肌保护作用,其效应呈剂量依赖性。
Objective To study the inhibitory effect of Shexiang Baoxin Pill on myocardial remodeling caused by cirrhosis and its mechanism. Methods Rat hepatic fibrosis model was induced by 3% (volume fraction) 40% CCl4 olive oil solution (3mL / kg, twice a week for 8 weeks). At the end of the second week, 5 rat liver tissues were randomly divided into HE staining and liver Fibrosis degree, model rats were ig musk pill 22.5,45 mg / kg for a total of 6 weeks, the end of the 8th week, respectively, the liver tissue of rats in each group, left ventricular myocardial histopathology and transmission electron microscopy The changes of hepatic and myocardial histopathology and myocardial ultrastructure in each group were observed and observed. The expressions of c-fos and c-jun mRNA and connective tissue growth factor (CTGF) in myocardium were detected by RT-PCR and immunohistochemistry. Changes in the expression of type I and type III collagen. Results There were different degrees of hepatic fibrosis and myocardial injury in the model rats. Compared with the model group, there was no significant difference (P> 0.05) in the degree of liver fibrosis between the low dose Shexiang Baoxin Pill group and the model group, but the degree of myocardial injury was relieved. The c-fos mRNA, c-jun mRNA, CTGF, And type III collagen decreased significantly (P <0.05, 0.01). The levels of c-fos mRNA, c-jun mRNA, CTGF, type I and type III collagen in the myocardium of high-dose Shexiang Baoxin Pill group were significantly lower than those in the low dose group (P <0.05) Lower than the low dose group (P <0.05,0.01). CONCLUSION: Myocardial immediate activation of cardiac myocytes in cirrhotic rats induces over-expression of CTGF and induces cardiac remodeling. Shexiangbaoxin Pill exerts myocardial protection by inhibiting immediate early gene expression in myocardium and decreasing myocardial CTGF levels in a dose-dependent manner Dependency.