ICOS信号介导的免疫反应在SHR大鼠肾纤维化中作用的实验研究  

Experimental study on effect of immune response mediated by ICOS signal in renal fibrosis of SHR

作　　者：钱小宝 王瑜[1] 梅仁彪[1] 张文杰[1] 马婕[1] 王晓瑜[1] 

机构地区：[1]安徽理工大学医学院基础医学系,淮南232001

出　　处：《中国免疫学杂志》2015年第12期1610-1615,共6页Chinese Journal of Immunology

基　　金：安徽高校省级自然科学重点研究项目(KJ2012A082);大学生创新创业训练计划项目(201310361101)

摘　　要：目的:初步探讨可诱导共刺激分子(Inducible costimulation molecule,ICOS)介导的免疫反应在原发性高血压肾损害中的作用。方法:采用无创尾动脉血压测量仪动态监测自发性高血压大鼠(Spontaneously hypertensive rats,SHR)及其野生对照组京都维斯塔尔大鼠(Wistar-Kyoto rats,WKY)的血压情况。应用ELISA法动态检测上述大鼠的24小时尿蛋白情况。采用免疫组化技术及RT-PCR法动态检测上述大鼠肾脏中ICOS蛋白及其mRNA的表达水平。应用免疫组化技术及ELISA法动态检测大鼠肾脏及血浆中IL-17A和TGF-β1的表达水平。采用HE及MASSON染色检测各期大鼠肾脏病理改变情况。结果:SHR大鼠从第6周开始血压及24小时尿蛋白值显著高于同期WKY大鼠。SHR大鼠肾脏中ICOS蛋白及其mRNA表达水平从第6周开始亦显著高于同期WKY大鼠,且其表达水平的动态变化均与SHR大鼠肾脏纤维化评分动态变化呈显著正相关关系(r A=0.813,PA<0.05;r B=0.753,PB<0.05)。SHR大鼠血浆和肾脏中IL-17A、TGF-β1的表达在10周、23周亦显著高于同期WKY大鼠。HE和MASSON染色结果显示,与WKY大鼠相比,SHR大鼠肾脏纤维化程度明显升高,在23周后两者差异具有显著性(P<0.05)。结论:在高血压导致的肾损害中,ICOS介导的免疫反应可能起重要的作用。Objective： To preliminarily study the immune response mediated by inducible costimulation molecule in the role of essential hypertensive renal damage. Methods： The blood pressure of spontaneously hypertensive rats and the wild control group（ Wistar-Kyoto rats） was dynamically monitored by noninvasive tail artery blood pressure measuring instrument. The urine protein of the rats in24 hours was dynamically detected by ELISA. The levels of ICOS protein and its mRNA in the rat＇s kidneys were dynamically detected by immunohistochemistry,RT-PCR,respectively. The levels of IL-17 A and TGF-β1 in the rat＇ s plasma and kidneys were dynamically detected by ELISA,immunohistochemistry,respectively. The renal pathological changes of the rats were detected by HE and MASSON staining. Results： The blood pressure and urine protein in 24 h of SHRs were significantly higher than that of group WKY from 6weeks. The expression of ICOS protein and its mRNA in SHRs were significantly higher than that of WKY rats from 6 weeks,and there are significantly positive correlations between the dynamic change of ICOS protein and its mRNA and renal fibrosis score of SHRs（ r A =0. 813,PA 0. 05; r B = 0. 753,P〈 0. 05）. The expression of IL-17 A and TGF-β1 in SHR＇ s plasma and kidneys were significantly higher than that of WKY rats at the weeks 10 and 23. HE and Masson staining showed that the degree of renal fibrosis of SHRs was significantly higher than that of WKY rats at 23 weeks. Conclusion： The immune response mediated by ICOS plays an important role in hypertensive renal damage.

关 键 词：可诱导共刺激分子 原发性高血压 自发性高血压大鼠 肾纤维化 

分 类 号：R392.11[医药卫生—免疫学]