扶正化瘀方对非酒精性脂肪性肝纤维化的治疗作用  

Fuzheng Huayu recipe on nonahoholic hiver fibrosis treatment

作　　者：李会[1] 南月敏[1] 王荣琦[1] 孔令波[1] 米红梅[1] 任伟光[1] 杜静华[1] 

机构地区：[1]河北医科大学第三医院中西医结合肝病科,石家庄050051

出　　处：《肝脏》2013年第8期526-529,共4页Chinese Hepatology

基　　金：Pearl Ocean Liver Fibrosis Grant(001)

摘　　要：目的观察扶正化瘀方对非酒精性脂肪性肝纤维化小鼠肝组织过氧化物酶体增殖物激活受体-／（peroxisomeproliferatoractivatedreceptor—gamma，PPAR7）和相关炎性因子及纤维化因子表达的影响，以探明扶正化瘀方阻止脂肪性肝纤维化进展的作用机制。方法选用7～8周龄健康雄性C57BI。／6J小鼠，高脂、蛋氨酸胆碱缺乏（methionineandcholinedeficient，MCD）饮食喂养8周，建立非酒精性脂肪性肝纤维化模型，分别采用扶正化瘀方、血红素氧合酶1（hemeoxygenase-1，HO1）激动剂血晶素、扶正化瘀方联合血晶素进行干预实验，以蛋氨酸胆碱充足饮食为对照组。HE染色及Masson染色观察肝脂肪变、炎性反应及纤维化程度；分别采用RT—PCR、实时定量RT—PCR和Western印迹检测肝组织PPAR7、Ii。1O、基质金属蛋白酶2（matrixmetalloproteinase2，MMP-2）和金属蛋白酶组织抑制因子1（tissueinhibitorofmatrixmetalloproteinase1，TIMP1）mRNA及蛋白的表达。结果模型组小鼠肝组织出现大泡性为主的混合性肝细胞脂肪变、点灶状肝细胞坏死及炎细胞浸润、汇管区纤维组织增生及窦周纤维化，肝组织PPAR7mRNA及蛋白表达水平较对照组显著降低，mRNA、MMP2和TIMP1mRNA及蛋白表达较对照组显著升高。应用扶正化瘀方、血晶素或扶正化瘀方联合血晶素干预后肝损伤显著改善，伴肝组织PPAR．ymRNA及蛋白表达上调（P〈O．05）及IL1（1mRNA、MMP2和TIMP1mRNA及蛋白表达下调（P〈0．05），尤以扶正化瘀方联合血晶素组效果显著。结论扶正化瘀方可通过调节PPAR—Y及相关炎性反应及纤维化因子的表达阻止非酒精性脂肪性肝纤维化的发生发展，尤以联合应用血晶素效果为佳。Objective To investigate the effects of Fuzheng Huayu recipe （FZHY） on the expression of peroxisome proliferatoactivated receptor-gamma （PPAR-y）, inflammatory and fibrotic related genes in mice with nonalcoholic steato hepatic fibrosis, and elucidate the mechanism of FZHY on inhibiting steatohepatic fibrosis. Methods C57BL/6J male mice of 7-8 weeks were fed high-fat, with methionine-choline deficient （MCD） diet for 8 weeks to induce nonalcoholic steato hepatic fibrosis. The mice were administrated with FZHY and/or heme oxygenase 1 （HO 1 ） chemical inducer （heroin）. Hepatic steatosis, inflammation and fibrosis were observed using HE staining and Masson staining. The mRNA and protein expression of PPAR-7, interleukin 10 （IL 10）, matrix metalloproteinase 2 （MMP 2）, and tissue inhibitor of matrix metalloproteinase-1 （TIMPd） were analyzed by RT PCR, quantitative real time PCR and western blot, respectively. Results Mice fed with MCD diet for 8 weeks exhibited severe hepatocyte macrosteatosis, spot or focal hepatocyte necrosis and inflammatory infiltration, fibrous septum and portal fibrosis, hepatic mRNA and protein level of PPAR y were signifi cantly decreased, IL-10 mRNA, MMP-2 and TIMP I mRNA and protein expression was significanthy higher than the con trol group. After FZHY and/or heroin treatment, the hepatic pathological changes were ameliorated with liver PPAR-7 mRNA and protein expression increased（P〈0.05） and IL 10 mRNA, MMP-2 and TMP 1 mRNA and protein danregulated （P〈0. 05）, especially in the mice treated with FZHY combinated with hemin. Conclusion FZHY, especially combined with hemin, could ameliorate nonalcoholic steatohepatic fibrosis through regulation of PPAR-y, inflammatory and fibroticrelated genes, which might serve as an effective therapeutic strategy for nonalcoholic steatohepatitis and fibrosis.

关 键 词：扶正化瘀方 非酒精性脂肪性肝炎 肝纤维化 过氧化物酶体增殖物激活受体-Γ 基质金属蛋白酶-2 金属蛋白酶组织抑制因子-1 

分 类 号：R259[医药卫生—中西医结合]