肿瘤坏死因子-α抗体对梗阻性黄疸大鼠肾脏IP_3R表达的影响

Effect of TNF-α McAb on the renal expression of IP_3R in the obstructive jaundice rats

目的研究肿瘤坏死因子-α(TNF-α)单克隆抗体对梗阻性黄疸大鼠肾功能的影响及机制。方法将60只雄性SD大鼠随机分成假手术组、模型组、干预组,采用胆总管结扎(CBDL)造梗黄模型,干预组于结扎后第2周开始腹腔注射TNF-α单克隆抗体[0.1 mg/(kg.2d)]。并于干预后1、2、3、4周麻醉动物,假手术组与5周模型组动物同批麻醉,留取肝和肾组织。采用HE染色确定模型建立情况,通过Western blot方法检测1,4,5-三磷酸肌醇受体(IP3R)的含量,免疫组织化学方法检测IP3R在肾组织的表达。结果 HE染色显示模型组和干预组肾间质有炎性细胞浸润,干预组较轻。免疫组化和Western blot显示模型组肾组织IP3R蛋白表达较多,干预组略下降,但均明显高于假手术组(P<0.05)。结论梗阻性黄疸时肾小球前小动脉平滑肌细胞内的IP3R蛋白的表达增强,而TNF-α单克隆抗体干预治疗可减轻IP3R表达增强的程度,部分减轻肾功能损害的发生。

Objective To study the effect of TNF-α McAb on the renal function in the obstructive jaundice rats and the associated mechanism. Methods 60 male Sprague Dawley rats were divided into three groups randomly： sham-opera- tion group, CBDL group and treatment group. These rats in treatment group began intraperitoneal injection of TNF-α McAb [ 0. 1 mg./（ kg ·2d） ] in the second week and were anesthetized at 1,2, 3, 4 week. Sham-operation group rats were anes- thetized at the same time with CBDL group at 5 week and all the hepatic tissue and nephridial tissue samples were kept. HE triehrome staining was used to determine the model establishment. The expression of inositol 1,4,5-triphosphate receptor （IP3R） in nephridial tissue was detected by immunohistochemistry and Western blot. Results HE results showed that there was inflammatory cells infiltrate in renal interstifium in CBDL group and treatment group, and had a little less than that in CBDL group. CBDL group compared with treatment group, there was much more positive protein expression of IP3 R, moreover they were also much higher than that of the sham group （ P 〈 0.05 ）. Conclusions When obstructive jaundice happens, the expression of IP3 R in glomcrulus arteriole smooth muscle cells increases. Using TNF-α McAb can lessen the expression of IP3 R in glomcrulus arteriole smooth muscle cells and improve the damage for obstructive jaundice rats＇ renal function partly.