姜黄素和γ-干扰素对肝纤维化大鼠肝组织病理变化及TIMP-1表达的作用  

Effects of Curcumin and γ-Interferon on the Pathologic Changes and Expression of Metalloproteinase-1 in the Livers of Rats with Fibrosis

作　　者：王华[1] 曾令兰[1] 陈莎燕[1] 朱励[1] 李淑莉[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院感染科实验室,武汉430022

出　　处：《微循环学杂志》2009年第3期28-30,F0003,共4页Chinese Journal of Microcirculation

摘　　要：目的:观察肝纤维化大鼠肝组织病理学变化及金属蛋白酶组织抑制因子-1(TIMP-1)的表达水平,探讨姜黄素和γ-干扰素及两者联合治疗抗肝纤维化的作用。方法:将40只雄性SD大鼠随机分为正常对照组、模型组和治疗组,治疗组中又分为姜黄素治疗、γ-干扰素治疗及联合治疗3个亚组,采用CCl4腹腔注射制作大鼠肝纤维化模型。各治疗组采取相应药物和剂量平行治疗4周,第10周末将各组大鼠处死,取肝组织切片HE染色观察组织病理学变化(包括肝纤维化程度);用半定量RT-PCR方法检测各组肝组织TIMP-1mRNA相对表达量。结果:肝组织病理学观察显示,模型组大鼠肝索排列紊乱,肝细胞变性坏死,汇管区和小叶内出现局限性纤维化,部分区域出现纤维纵隔,甚至假小叶形成,纤维化分级为Ⅳ～Ⅴ级(Ⅴ级为主),TIMP-1mRNA相对表达量较正常对照组明显升高(P<0.01);各治疗组肝组织病理变化明显改善,肝细胞变性坏死减少,肝纤维化程度明显减轻(以Ⅲ级为主),TIMP-1mRNA表达量明显低于模型组(P<0.01)。结论:姜黄素和γ-干扰素及两者联合治疗均能减轻肝纤维化大鼠组织病理学变化并下调肝组织TIMP-1mRNA表达,改善和逆转肝纤维化进程。Objective:To investigate the role of curcumin and γ-interferon and drug combination in the anti-fibrosis by observing the expression of metal proteinase-1(TIMP-1) and pathologic changes in hepatic tissue in experimental rats.Method:40 male Sprague-Dawley rats were randomly divided into 3 big groups:normal group,model group and treatment group(including curcumin group,γ-interferon group and combination therapy group).The experimental hepatic fibrosis model was induced by intraperitoneal injection of carbon tetrachloride oil solution.All rats were used in parallel treatment of drug and dose for 4 weeks in treatment group.All groups of rats were sacrificed after 10th weeks.HE staining of hepatic tissue,pathological changes were observed;TIMP-1 mRNA was determined by semi-quantitative polymerase chain reaction(RT-PCR).Results:Pathology of liver tissue in model group showed:disorder of hepatic cords,necrosis of hepatocytes,limited fibrosis was found at portal area and hepatic lobule,fibrous connective tissue was found in some places,and even the pseudolobule was found.Fibrosis grading was grade Ⅳ～Ⅴ(Ⅴ level is the main).Expression of TIMP-1 mRNA relatively was higher than the normal group(P<0.01).The pathological changes of liver tissue in treatment group were significantly improved,necrosis of liver cells and the degree of liver fibrosis(Ⅲ level is the main) were reduced.Expression of TIMP-1 mRNA was significantly lower than that of model group(P<0.01).Conclusion:All treatment groups were to alleviate the pathological changes and reduced expression of TIMP-1 mRNA in rat liver,thereby improving and reversing the process of liver fibrosis.

关 键 词：TIMP-1表达 肝纤维化 大鼠肝脏 组织病理变化 姜黄素 Γ-干扰素 金属蛋白酶抑制因子 基质金属蛋白酶 

分 类 号：R575[医药卫生—消化系统] R575.2[医药卫生—内科学]