埃克替尼对二甲基亚硝胺诱导肝纤维化大鼠的作用  

Effect of icotinib on rat liver fibrosis induced by dimethylnitrosamine

作　　者：彭渊[1] 沈丽[1] 陶艳艳[1] 刘成海[1,2,3,4] 

机构地区：[1]上海中医药大学附属曙光医院肝病研究所,上海201203 [2]上海高校中医内科学E-研究院,上海201203 [3]上海市中医临床重点实验室,上海201203 [4]肝肾疾病病证教育部重点实验室,上海201203

出　　处：《中国新药与临床杂志》2015年第5期346-350,共5页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家科技重大专项(2014ZX10005001);上海市医学领军人才计划(LJ10005)

摘　　要：目的观察埃克替尼对二甲基亚硝胺(DMN)大鼠实验性肝纤维化的影响。方法 48只雄性Wistar大鼠随机分为正常组(n=10)、模型组(n=14)、扶正化瘀组(n=12)与埃克替尼组(n=12)。模型组、扶正化瘀组和埃克替尼组以DMN 10μg·kg-1体重腹腔注射复制肝纤维化模型,每周连续3 d,连续4周;首次注射剂量为正常剂量2/3。自造模第3周开始,扶正化瘀组与埃克替尼组分别给予扶正化瘀胶囊4.0 g·kg-1、埃克替尼5 mg·kg-1灌胃,每周连续7 d,连续4周。HE染色与胶原染色观察肝组织炎症与胶原沉积,试剂盒检测血清肝功能水平,Jamall法测定肝组织羟脯氨酸(HYP)含量。荧光定量PCR检测肝组织α-平滑肌肌动蛋白(α-SMA)与转化生长因子-β(TGF-β)表达。结果与正常组相比,模型组大鼠的腹水发生率、血清总胆红素(T.Bil)含量、丙氨酸转氨酶(ALT)与天冬氨酸转氨酶(AST)活性、肝组织HYP含量均明显升高(P<0.01),血清白蛋白(Alb)含量明显减少,肝组织炎症及胶原沉积加重(P<0.01),肝组织α-SMA及TGF-βm RNA表达增多(P<0.05)。埃克替尼可明显减少造模大鼠腹水发生率,降低ALT、AST、T.Bil水平和肝组织HYP(P<0.05),减轻肝组织炎症及胶原沉积(P<0.05),下调肝组织α-SMA及TGF-βm RNA表达(P<0.05)。结论埃克替尼能够改善DMN诱导的大鼠实验性肝纤维化。AIM To investigate the effect of icotinib on rat liver cirrhosis induced by dimethylnitrosamine（ DMN）. METHODS Forty-eight male Wistar rats were randomly divided into four groups as follows： control group（n = 10）, model group（n = 14）, Fuzhenghuayu（FZHY） group（n = 12） and icotinib group（n =12）. Liver fibrosis was induced with DMN 10 μg·kg-1intraperitoneally in the four groups except control group,3 consecutive days per week for 4 weeks. The dosage of the first injection of DMN was 2/3 of the normal dosage.Two weeks after DMN intoxication, icotinib was administered orally by gavage, once a day, for 4 weeks at dose level of 5 mg·kg-1of body weight. Simultaneously, the FZHY group was treated with FZHY at dose level of 4.0 g crude drug·kg-1orally. Liver inflammation and collagen deposition were evaluated with HE staining and Sirius red staining. Serum liver functions were determined by kits. The contents of hepatic hydroxyproline（HYP） were measured by Jamall’ s method. Levels of α-smooth muscle actin（ α-SMA） and transforming growth factor-β（ TGF-β） were investigated by real-time fluorescence quota PCR. RESULTS The occurrence rate of ascites,serum T.Bil content, ALT and AST activities, liver inflammation and deposition of collagen, liver HYP content, and α-SMA and TGF-β m RNA levels were all significantly increased（P 〈 0.05） in the model group,when compared with those of the control group, while the serum Alb content was significantly decreased（P 〈0.01）. Icotinib treatment significantly reduced the occurrence rate of ascites, ameliorated serum ALT, AST and T.Bil（ P 〈 0.05）, elevated levels of serum Alb（ P 〈 0.05）, relieved liver inflammation and collagen deposition and down-regulated expressions of α-SMA and TGF-β m RNA in liver tissue（ P 〈 0.05）.CONCLUSION Icotinib has good anti-fibrotic effects on DMN-induced liver cirrhosis in rats.

关 键 词：埃克替尼 二甲基亚硝胺 肝硬化 大鼠 

分 类 号：R575.2[医药卫生—消化系统] R962[医药卫生—内科学]