糖尿病肾病大鼠肾组织MMP-9表达及意义  

Expression and mechanism of MMP-9 in kidney tissues of rats with diabetic nephropathy

作　　者：凌厉[1] 陈立波[1] 劳国娟[2] 张长宁[1] 

机构地区：[1]广东医学院附属深圳南山医院,广东深圳518052 [2]中山大学孙逸仙纪念医院

出　　处：《山东医药》2016年第36期28-31,I0001,共5页Shandong Medical Journal

基　　金：国家自然科学基金青年科学基金资助项目(81400818);深圳市卫生计生系统科研项目(201402128)

摘　　要：目的探讨基质金属蛋白酶9(MMP-9)在糖尿病肾病发生、发展中的作用。方法将60只Wistar大鼠随机分为两组,对照组24只、模型组36只,模型组一次性腹腔注射链脲佐菌素(150 mg/kg)制备糖尿病模型,成模24只;对照组注射等量的柠檬酸缓冲液。给药1、2、4、8周时,两组分别随机选择6只大鼠,取其肾组织观察病理学变化,标本行HE染色,采用免疫组化法检测肾组织MMP-9表达,计数每个肾小球内MMP-9染色阳性的足细胞(MMP-9阳性足细胞)数量。采用RT-PCR法检测肾组织TET1蛋白、活化因子蛋白1(AP-1)mRNA相对表达量。结果模型组给药1、2、4、8周时可见肾小球体积逐渐增大,基底膜逐渐增厚,毛细血管袢逐渐扩张,伴随肾小管扩张或萎缩,可见轻度纤维化。对照组给药1周时MMP-9阳性足细胞数量为(0.47±0.31)个;模型组给药1、2、4、8周时MMP-9染色阳性足细胞数量分别为(2.75±1.29)、(4.59±1.63)、(7.95±2.36)、(15.61±2.77)个,呈逐渐增高趋势,且均高于对照组,组间及组内比较P均<0.05。模型组给药后1、2、4、8周时肾组织AP-1、TET1相对表达量呈逐渐增高趋势,且均高于同时间点对照组,组间及组内比较P均<0.05。结论 MMP-9高表达参与了糖尿病肾病的发生、发展,激活AP-1、TET1基因可能是其作用机制。Objective To investigate the effect of matrix metalloproteinase 9（ MMP-9） expression in the occurrence and development of diabetic nephropathy of rats. Methods Sixty Wistar rats were randomly divided into two groups： the control group（ n = 24） and the model group（ n = 36）. Rats in the model group received intraperitoneal injection of STZ（ 150 mg/kg） to establish the diabetes models while rats in the control group received equal dose of citrate buffer. At 1,2,4,and 8 weeks after treatment,6 rats were randomly selected from each group and their renal tissues were collected and analyzed by HE staining,immunohistochemistry for MMP-9 expression. And we counted the sertoli cells with MMP-9 positive staining in glomeruli（ MMP-9 positive sertoli cells）. RT-PCR was used to detect the TET1 and AP-1 mRNA expression. Results At 1,2,4,and 8 weeks after drug administration,rats of the model group showed gradually enlarged renal glomeruli,thickened basement membrane,and expanded capillary loops,with visible tubular dilatation or atrophy and mild fibrosis. MMP-9-positive cells in each renal glomerulus of the control group was 0. 47 ± 0. 31 at 1 week after drug administration; while this number of the model group was 2. 75 ± 1. 29,4. 59 ± 1. 63,7. 95 ± 2. 36 and 15. 61 ± 2. 77 respectively at 1,2,4,and 8 weeks after drug administration,which showed an increasing tendency and was significantly higher than that of the control group（ all P〈0. 05）. The relative mRNA levels of AP-1 and TET1 of the model group showed an increasing tendency,which were also significantly higher than those of the control group at the same time（ all P〈0. 05）.Conclusion The high expression of MMP-9 may play a significant role in the development and progression of diabetic nephropathy,possibly through the activation of AP-1 and TET1.

关 键 词：糖尿病肾病 基质金属蛋白酶9 活化因子蛋白1 TET1蛋白 

分 类 号：R587.1[医药卫生—内分泌]