γ-干扰素对梗阻性积水肾间质纤维化的治疗作用  

Experimental study on the protective effect of IFN-γ on renal interstitial fibrosis following unilateral ureteral obstruction

作　　者：刘刚[1] 姚颐[2] 张杰[2,4] 谭大清[3] 彭建平[2] 

机构地区：[1]广西壮族自治区人民医院泌尿外科,530021 [2]武汉大学人民医院泌尿外科 [3]湖北民族学院附属医院泌尿外科 [4]武汉大学生命科学院病毒学国家重点实验室

出　　处：《中华实验外科杂志》2008年第4期497-499,共3页Chinese Journal of Experimental Surgery

基　　金：高等学校博士学科点专项科研基金资助项目（20060486054）

摘　　要：目的探讨γ干扰素（IFN-γ）对梗阻性肾积水肾间质纤维化的抑制作用及其可能的机制。方法将65只雄性SD大鼠随机分成4组：治疗组（20只）、模型组（20只）、药物对照组（20只）、假手术组（5只）。在建模和给药后的第3、7、14、21、28天，每组各随机处死动物4只（假手术组1只）。采用苏木素-伊红（HE）和Masson染色观察病变肾脏间质纤维化的情况；采用聚合酶链反应（RT—PCR）技术检测肾组织中转化生长因子-β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）和Ⅰ型胶原（Col—Ⅰ）的mRNA表达情况；免疫组织化学法观察以上三种蛋白的变化。结果模型组大鼠术后肾间质逐渐出现纤维化改变，并随梗阻时间的延长逐渐加重，TGF-β1、α-SMA和Col-Ⅰ的mRNA和蛋白表达亦逐渐升高。第14天，模型组TGF-β1和叶SMA的表达量达到高峰，28d时各指标的表达均达到最高，TGF—β1、α-SMA和Col—Ⅰ分别为51．84％、72．59％和68．73％。治疗组各指标在不同时间点均低于模型组，第28天时，三项指标依次为33．84％、32．59％和48．73％，与模型组比较P〈0．05。Banff评分显示治疗组间质纤维化程度明显减轻（P〈0．01）。其余两组未见肾间质纤维化改变。结论IFN-γ具有减轻积水后肾间质纤维化程度的作用，该作用与其下调TGF-β1的表达、抑制肌成纤维细胞（MyoF）激活和减少Col—Ⅰ生成有关。Objective To investigate the therapeutic mechanism of IFN-γ on renal interstitial fibrosis in rats with unilateral ureteral obstruction （UUO）. Methods Sixty-five Sprague-Dawley male rats were randomly assigned to treatment group （ n = 20）, model group （ n = 20）, control group （ n = 20）, and sham operation group （n =5）. All rats were sacrificed randomly on 3,7,14,21,28 days （ 1 rat in sham operation group every time, yet 4 in other groups） and the hudronephrotic kidney was excised. The extents of renal interstitial fibrosis were observed after sections of renal tissue were stained by hematoxylin and cosinas well as masson. RT-PCR was performed to detect the mRNA expression of transforming growth factor-betal （TGF-β1）, α-smooth muscular actin （α-SMA） and Collagen-Ⅰ （Col-Ⅰ）. Immunohistochemical staining was performed to assay the expression of TGF-β1, α-SMA and Col-Ⅰ. All data were analyzed by SPSS 12.0. Results The extent of renal interstitial fibrosis and the mRNA expression of TGF-β1 ,α-SMA and Col-Ⅰ in renal interstitial tissue became more obvious as time went by gradually in treatment group as compared with model group （ P 〈 0.05 ）. At the day of 28, the mRNA expression of α-SMA, Col-Ⅰ and TGF-β1 in model group was 68.73% ,72.59% and 51.84% respectively,and that in treatment group was 48.73% ,32.59% and 33.84% respectively. Banff score showed that the fibrotic degree in treatment group decrease significantly （P 〈 0.01 ）. There was no renal interstitial fibrosis in other two groups. Conclusion These data suggested that IFN-γ could down-regulate the expression of TGF-β1 ,α-SMA and Col- Ⅰ,and restrain renal interstitial fibrosis.

关 键 词：肾间质纤维化 Γ-干扰素 Ⅰ型胶原 转化生长因子-Β 

分 类 号：R285.5[医药卫生—中药学]