三甲益肝冲剂和螺内酯对大鼠肝纤维化预防作用  

Experimental study about prophylactic effects of combination of Sanjia-Yigan granule and spironolactone on hepatic fibrosis in rats

作　　者：申保生[1] 乔汉臣[1] 杨道坤[1] 

机构地区：[1]新乡医学院第一附属医院感染科,河南卫辉453100

出　　处：《新乡医学院学报》2005年第5期429-432,F0003,共5页Journal of Xinxiang Medical University

摘　　要：目的探讨复方中药三甲益肝冲剂(S-JG)联合螺内酯对肝纤维化的预防机制和效果。方法雄性SD大鼠50只,随机分为模型组(A组),螺内酯组(B组),S-JG组(C组),S-JG联合螺内酯组(D组)和正常对照组(E组)各10只。A、B、C、D各组均以二甲基亚硝胺(DMN)腹腔注射诱导大鼠肝纤维化模型;A组造模同时给予生理盐水灌胃,B组和C组造模同时分别给予螺内酯和S-JG灌胃;D组造模同时给予S-JG和螺内酯灌胃;E组腹腔注射等量生理盐水并用自来水灌胃,共4周。4周后取肝组织标本,行HE和Masson染色,免疫组化法检测α-平滑肌肌动蛋白(α-SMA)、基质金属蛋白酶2(MMP-2)和金属蛋白酶组织抑制因子-1(TIMP-1)。结果(1)肝脏病理学改变:A组可见较粗的纤维间隔向肝小叶伸展;B、C组可见稍细的纤维间隔;D组可见更细的纤维间隔从汇管区向肝小叶伸展。(2)Masson染色胶原纤维面积比较:A、B、C、D组胶原面积比E组显著增加(P<0.01),应用药物组胶原面积较A组均减轻(P<0.01),以联合用药组最明显,B组与C组比较P>0.05,余组间比较P<0.01;(3)-αSMA、MMP-2和TIMP-1免疫组化检测结果:A组均为强阳性表达,B组和C组表达少于A组,D组表达很少,比较有显著差异(P<0.01)。结论S-JG和螺内酯可能通过部分抑制肝星状细胞的活化从而抑制MMP-2和TIMP-1的表达发挥抗肝纤维化作用,两者效果相似,但联合用药效果更好。Objective To explore the mechanisms and preventive effects of Sanjia-yigan granule （S-JG）and spironolactoneon hepatic fibrosis, Methods Fifty male SD rats were randomly divided into five groups： The dimethyl-nitrosame （DMN, 2 ml·kg^-1 ,once daily, 3 days serially a week） was injected intraperitoneally for 4 weeks in group A to construct the models of hepatic fibrosis; The S-JG in group B and spironolactone in group C were respectively given per I.G. ,and the hepatic fibrosis were induced as group A; Sanjia yigan granule combined with spironolactone group were given per I, G, , and the hepatic fibrosis were induced in group D as group A; and normal saline was given per I, G, for 4 weeks in group F as control group. The expressions of α-smooth muscle action（α-SMA）, matrix metalloproteinase （ MMP-2 ） and tissue inhibitor of metalloproteinases-1 （TIMP-1） were observed by immunohistoehemical staining. Results （1） The pathological changes of liver： The fibrosis interval of group A was wider than that of group B, C and D; That of group B, C was wider than that of group D; The fibrosis interval of group B was equal to that of group C. （2） The comparison of collagen area in Masson：The comparison of collagen area in group B and C were less than that of group A （ P 〈 0.05）, and that of group D was less than that group B and C （P〈0.05）. （3） The results of immunohistoehemical staining： The expressions of α-SMA, MMP-2 and TIMP-1 were strong positive in group A; The expressions in group B and C were lower than that of group A; The expressions in group D were minimal and Iower than that of group B and C. Conclusion The S-JG and spironolactone could prevent the hepatic fibrosis by suppressing the activation of HSC and diminishing the expressions of MMP-2 and TIMP-1. The preventive effects of both medicine is similar, but the effect of combined ttse is the best.

关 键 词：肝纤维化 三甲益肝冲剂 螺内酯 肝星状细胞 基质金属蛋白酶 金属蛋白酶组织抑制因子 

分 类 号：R256.49[医药卫生—中医内科学]