麝香保心丸对肝硬化大鼠心肌组织即早基因与结缔组织生长因子的影响

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。

Effects of Shexiang Baoxin Pills on myocardial tissue immediate early gene and connective tissue growth factor in rats with hepatic cirrhosis

Objective To investigate the inhibition of Shexiang Baoxin Pills(SBP) on myocardium reconstruction due to hepatic cirrhosis and its mechanism.Methods Model of hepatic cirrhosis rats was established by sc injection with 40% CCl4 of olive oil solution(3 mL/kg,twice a week for eight weeks).After two weeks of the first injection,five rats were executed to confirm the formation of hepatic fibrosis by HE staining,and the rest of rats were randomly and equally divided into model,low-,and high-dose SBP groups.Low-and high-dose groups were respectively ig administrated with SBP at volumes of 22.5 and 45 mg/(kg.d) for six weeks,whereas the rats of model group were not given any treatment.At the end of the 8th week,all rats were sacrificed and a part of liver tissue and myocardium tissue were preserved.Transmission electron microscope(TEM) technique was applied to observing the changes of hepatic and cardiac histopathology and myocardial ultramicrostructure;RT-PCR and immunohistochemical techniques were applied to analyzing the expression of myocardial c-fos mRNA,c-jun mRNA,and the contents of myocardial connective tissue growth factor(CTGF),types I and III collagen in all groups.Results Hepatic fibrosis and myocardial injury were in different degrees among the three groups.Compared to model group,low-dose SBP treatment could not relieve the degree of hepatic fibrosis(P > 0.05).The degree of myocardial injury and the content of myocardial c-fos and c-jun mRNA,CTGF as well as types I and III collagen were obviously reduced(P < 0.05,0.01).Compared to low-dose group,the degrees of hepatic fibrosis and myocardial injury were further relieved(P < 0.05) and the content of myocardial c-fos and c-jun mRNA,CTGF as well as types I and III collagen were reduced significantly with high-dose SBP treatment(P < 0.05,0.01).Conclusion Hepatic cirrhosis in rats may lead to myocardium reconstruction by stimulating the expression of immediate early gene and promoting the overexpression of CTGF in myocardium.SBP may protect myocardium through inhibiting the expression of myocardial immediate early gene,which could decrease the level of myocardial CTGF in a dose-dependent manner.