马洛替酯防治大鼠肝纤维化的作用和机制  

Effect and mechanism of malotilate in prevention and treatment of hepatic fibrosis in rats

作　　者：康毅[1] 王晨晓[2] 罗伟生[2] 黄红[2] 黄旭平[2] 

机构地区：[1]广西中医药大学第一附属医院脾胃病科,南宁市530022 [2]广西中医药大学,南宁市530001

出　　处：《广西医学》2015年第6期744-748,共5页Guangxi Medical Journal

基　　金：国家自然科学基金(81360530)

摘　　要：目的观察马洛替酯对二甲基亚硝胺(DMN)诱导的大鼠肝纤维化的防治效果,并探讨其可能的机制。方法 60只SD大鼠随机分为正常对照组、模型组、秋水仙碱组和马洛替酯组。正常对照组不造模,其余各组用DMN腹腔注射诱导大鼠肝纤维化模型,造模同时,马洛替酯组用马洛替酯混悬液灌胃(0.1 g/kg,加适量生理盐水),秋水仙碱组用秋水仙碱混悬液灌胃(0.1 mg/kg,加适量生理盐水),正常对照组及模型组给予等体积生理盐水灌胃,1次/d,共6周。6周后,Masson染色观察肝组织纤维化程度;免疫组化法检测肝组织α-平滑肌肌动蛋白(α-SMA)显色指数;酶联免疫吸附法(ELISA)检测血清转化生长因子-β1(TGF-β1)、结缔组织生长因子(CTGF)水平,实时荧光定量PCR检测肝组织TGF-β1、CTGF mRNA表达量。结果马洛替酯组、秋水仙碱组肝纤维化评分均低于模型组(P<0.05),并且马洛替酯组较秋水仙碱组低(P<0.05);马洛替酯组、秋水仙碱组α-SMA显色指数均低于模型组(P<0.05),且马洛替酯组低于秋水仙碱组(P<0.05);马洛替酯组、秋水仙碱组血清TGF-β1、CTGF水平和肝组织TGF-β1、CTGF mRNA表达均明显低于模型组(P<0.01);马洛替酯组与秋水仙碱组比较,差异无统计学意义(P>0.05)。结论马洛替酯可显著抑制DMN诱导的大鼠肝纤维化形成,其机制可能与下调促肝纤维化因子TGF-β1、CTGF的表达、抑制肝星状细胞的增殖与活化有关。Objective To observe the preventive and therapeutic effect of malotilate on dimethylnitrosamine（DMN）-induced hepatic fibrosis in rats,and to explore its underlying mechanism.Methods Sixty SD rats were randomly divided into normal control group,model group,colchicine group and malotilate group.No rat model was developed in the normal control group,while the rat mode of hepatic fibrosis was induced by intraperitoneal injection with DMN in the other groups.Meanwhile,malotilate group was given mixed suspension of malotilate（0.1 g/kg） and normal saline by gavage once a day for six weeks,colchicine group was given mixed suspension of colchicine（0.1 mg/kg） and normal saline by gavage once a day for six weeks,and normal control group and model group were given the same volume of normal saline by gavage once a day for six weeks.Six weeks later,Masson staining was used to observe the fibrosis in liver tissues,immunohistochemistry to determine the color rendering index of alpha-smooth muscle actin（α-SMA） in liver tissues,enzyme-linked immunosorbent assay（ELISA） to detect the levels of serum transforming growth factor β1 （TGF-β1 ） and connective tissue growth factor （CTGF）,and real-time fluorescence quantitative PCR to detect the expression levels of TGF-β1 and CTGF mRNA in liver tissues.Results The score of hepatic fibrosis was lower in the malotilate group and colchicine group in contrast with that in the model group（P〈 0.05）.Conclusion Malotilate could significantly suppress the hepatic fibrosis induced by DMN in rats.Its potential mechanism might be associated with the down-regulation of TGF-β1 and CTGF expressions as well as inhibiting the proliferation and activation of hepatic satellite cells.

关 键 词：马洛替酯 肝纤维化 Α-平滑肌肌动蛋白 转化生长因子-Β1 结缔组织生长因子 

分 类 号：R965[医药卫生—药理学]