矮地茶黄酮抗二甲基亚硝胺诱导大鼠肝纤维化作用及机制研究  

Study on the antagonistic effects and mechanism of flavonoids from Ardisia japonica (Hornsted) BL. on liver fibrosis in rats induced by dimethylnitrosamin

作　　者：李志超 曹庆生[2] 吴卫[3] 高雅[3] 张可锋[3] LI Zhichao;CAO Qingsheng;WU Wei;GAO Ya;ZHANG Kefeng(Yutian Traditional Chinese Medical Hospital,Yutian Hebei 064100,China;Yutian Hospital,Yutian Hebei 064100,China;Guilin Medical University,Guilin Guangxi 541004,China)

机构地区：[1]河北省玉田县中医医院,河北玉田064100 [2]河北省玉田县医院,河北玉田064100 [3]桂林医学院,广西桂林541000

出　　处：《中兽医医药杂志》2019年第2期17-21,共5页Journal of Traditional Chinese Veterinary Medicine

基　　金：国家自然科学基金(81760704)

摘　　要：目的:研究矮地茶黄酮(FAJ)对二甲基亚硝胺(DMN)诱导的大鼠肝纤维化(HF)的保护作用及机制。方法:随机将大鼠分为正常组、模型组、秋水仙碱组(0.1 mg/kg)、FAJ高剂量组(600 mg/kg)、FAJ中剂量组(400 mg/kg)、FAJ低剂量组(200 mg/kg),除正常组外,其余各组腹腔注射0.5%DMN建立大鼠肝纤维化模型,FAJ各剂量组同时给予FAJ干预,1次/d,至实验结束。实验结束后,采集大鼠血液及肝组织标本,检测各组大鼠血清中谷丙转氨酶(ALT))、谷草转氨酶(AST)、超氧化物歧化酶(SOD)和丙二醛(MDA)、透明质酸(HA)、层黏蛋白(LN)水平,免疫组化方法检测各组大鼠肝脏转化生长因子-β1(TGF-β1)表达,观察各组大鼠肝脏组织病理学变化,探讨FAJ对DMN诱导的大鼠肝纤维化的保护作用及机制。结果:与模型组相比,FAJ高剂量组、FAJ中剂量组、FAJ低剂量组大鼠血清中ALT、AST、MDA、HA、LN水平显著降低(P<0.01,P<0.05);FAJ高剂量组、FAJ中剂量组中SOD水平显著升高(P<0.01),FAJ低剂量组SOD虽升高,但无显著性差异(P>0.05);病理切片显示,FAJ干预后肝组织内炎症细胞浸润和纤维化程度明显改善;免疫组化图像显示FAJ各剂量组TGF-β1表达下降。结论:FAJ对DMN诱导的大鼠肝纤维化具有保护作用且呈剂量依赖型,其作用机制可能与抗氧化、抑制肝星状细胞活化有关。Objective:To study the protective effect and mechanism of flavonoids from Ardisia japonica(Hornsted)BL.(FAJ)on dimethylnitrosamine(DMN)-induced hepatic fibrosis in rats,so as to provide scientific basis for clinical rational drug use and resource development in the future. Methods:Rats were randomly divided into normal group,model group,colchicine group(0.1 mg/kg),FAJ(600 mg/kg,400 mg/kg,200 mg/kg) groups. Except for normal group,each group was intraperitoneally injected with 0.5% DMN to establish hepatic fibrosis model in rats,and FAJ intervention was performed once a day until the end of the experiment. At the end of the experiment,blood and liver tissue samples were collected from the rats. Serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD) and malondialdehyde(MDA),andhyaluronan were detected in each group of rats. The level of acid(HA)and laminin(LN)was detected by immunohistochemistry.The expression of transforming growth factor-β1(TGF-β1)in liver of rats in each group was examined. Histopathological changes of liver in rats of each group were observed by pathology. And protective effect and mechanism of FAJ on DMN-induced hepatic fibrosis in rats was investigated. Results :Compared with the model group,the serum levels of ALT,AST,MDA,HA,and LN in the FAJ(600 mg/kg,400 mg/kg) group were significantly lowed(P <0.01,P <0.05),and the SOD level was significantly increased(P <0.01),the serum levels of ALT,AST,MDA,HA,and LN in the FAJ(200 mg/kg) were significantly lowed(P <0.01,P <0.05),the level of SOD was increased,but there was no significant difference(P >0.05).Pathological sections showed that the degree of inflammatory cell infiltration and fibrosis in liver tissue was significantly improved after FAJ intervention. Immunohistochemical images showed that the expression of TGF-β1 was decreased in each dose group of FAJ. Conclusion:FAJ has a protective effect on DMN-induced liver fibrosis in rats and was dose-dependent. Its mechanism of action may be related to anti

关 键 词：矮地茶黄酮 二甲基亚硝胺 肝纤维化 作用机制 

分 类 号：S853.74[农业科学—临床兽医学]