Smad7和尿激酶型纤溶酶原激活剂基因共表达对大鼠肝纤维化的治疗作用  

The therapeutic effect of Smad7 and urokinase-type plasminogen activator gene co-expression on rat liver fibrosis

作　　者：汪保灿[1] 孙超[1] 陈颖伟[1] 孙巧玲[1] 陈源文[1] 宗春华[1] 李定国[1] 

机构地区：[1]上海交通大学医学院附属新华医院消化科,200092

出　　处：《中华消化杂志》2007年第11期752-755,共4页Chinese Journal of Digestion

摘　　要：目的观察Smad7和尿激酶型纤溶酶原激活剂(uPA)基因共表达对CCl_4诱导大鼠肝纤维化的治疗作用。方法40只SD大鼠皮下注射CCl_4建立肝纤维化模型。将动物分为模型组、Ad Smad7/uPA组(尾静脉注射AdSmad7/uPA)、AdSmad7组(尾静脉注射AdSmad7)和Ad GFP组[尾静脉注射仅表达绿色萤光蛋白(GFP)的腺病毒载体],每组10只,另取10只大鼠作为正常对照组。采用放射免疫法测定血清Ⅲ型前胶原(PCⅢ)和层粘连蛋白(LN)水平;碱水解法检测肝组织羟脯氨酸含量;免疫组化法检测肝组织Smad7和uPA表达;天狼星红染色法检测肝纤维化程度。结果注射3d后,AdSmad7/uPA组肝组织Smad7和uPA表达量均显著增加,血清ALT、AST、PCⅢ、LN和羟脯氨酸水平较AdGFP和AdSmad7组明显下降(P值均<0.05)。AdSmad7/uPA组的肝纤维化面积为(5.96±2.72)%,明显低于AdGFP组的(13.32±2.47)%和AdSmad7组的(8.73±2.30)%(P值均<0.05)。结论Smad7和uPA双基因共表达可胁同阻断CCl_4诱导大鼠肝纤维化进程。Objective To investigate the therapeutic effects of Smad7 and urokinase-type plasminogen activator（uPA）co-expression on CCl4-induced rat liver fibrosis. Methods Forty SD rats were subcutaneously injectied of 40% CCl4 every three days for 8 weeks. The rats were then divided into model group, AdSmad7/uPA group（injected with AdSmad7/uPA via tail vein）, AdSmad7 group（injected with AdSmad7 via tail vein）or AdGFP group（injected with AdGFP via tail vein）. Ten healthy rats were served as control. The serum levels of procollagen Ⅲ （PCⅢ）and laminin（LN）were determined by radioimmunoassay, and the hydroxyproline level in liver tissues were examined by alkaline hydrolysis. The expressions of Smad7 and uPA in tissue were examined by immunohistochemistry and fibrosis area was stained with Sirius red. Results The expressions of Smad7 and uPA protein were significantly higher in AdSmad7/uPA group than that in AdGFP group after 3 days. Serum levels of ALT, AST, PC Ⅲ and LN were significantly decreased in AdSmad7/uPA group compared to Smad7 and AdGFP groups （all P value 〈 0.05）. The fibrosis area in AdSmad7/uPA group[（5.96± 2.72）%]was significantly less than AdGFP group[（13.32±2.47）%] and AdSmad7 group[（8.73±2.30）%]. Conclusion Smad7 and uPA coexpression may synergistically inhibit liver fibrosis induced by CC14 in rats.

关 键 词：肝纤维化 尿激酶型纤溶酶原激活剂 SMAD7 基因治疗 

分 类 号：R575.2[医药卫生—消化系统]