Fgl-2凝血酶原酶介导的微血栓形成在2型糖尿病大鼠肾脏损害中的作用  

Expression and Significance of Fgl-2 Prothrombinase in the Renal Tissue of Diabetic Rats

作　　者：汪艳[1] 王朝晖[1] 李晓卫[1] 刘晓倩[1] 苏冠华[1] 刘辉[1] 熊信林[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院心血管内科,武汉430022

出　　处：《微循环学杂志》2008年第3期12-15,F0002,共5页Chinese Journal of Microcirculation

基　　金：国家973重点基础研究发展规划基金资助项目(项目编号:2007CB512000;子课题编号:2007CB512005)

摘　　要：目的:观察纤维蛋白原样-2(Fgl-2)凝血酶原酶在糖尿病大鼠肾脏中的表达及其病理变化,探讨Fgl-2凝血酶原酶介导的微血栓形成在糖尿病肾脏微血管病变中的作用。方法:实验大鼠随机分为正常对照组(NC组)和2型糖尿病组(T2DM组)。建立T2DM大鼠模型,分别于实验第19周、第23周、第28周处死大鼠,测定24h尿蛋白、血肌酐(Cr)、尿素氮(BUN)、相对肾重;HE、PAS、MASSON染色观察不同病程T2DM组及NC组大鼠的肾脏病理改变,检测大鼠肾脏微血管内血栓形成,计算单位肾小球面积内微血栓所占阳性面积比例;以逆转录PCR方法、免疫组织化学方法测定Fgl-2凝血酶原酶在T2DM大鼠肾脏组织细胞上的表达,并将其表达的平均光密度值与单位肾小球内微血栓阳性面积比例进行相关性分析。结果:T2DM组大鼠Cr、BUN、相对肾重、24h尿蛋白均升高,Fgl-2凝血酶原酶的表达量亦明显增多,主要表达在T2DM大鼠的肾小球毛细血管内皮细胞及肾间质微血管内皮细胞。病理组织学检查显示T2DM大鼠肾小球肥大、系膜扩张、肾小球基底膜增厚、细胞外基质增生、肾小球毛细血管微血栓形成,且微血栓阳性面积比例明显高于NC组。分析显示Fgl-2凝血酶原酶的蛋白表达量与单位肾小球内微血栓阳性面积比例呈正相关。结论:首次发现Fgl-2凝血酶原酶mRNA及蛋白质在T2DM大鼠肾脏中表达上调,与单位肾小球内微血栓阳性面积比例呈正相关,提示Fgl-2凝血酶原酶介导的肾脏内微血栓形成可能促进糖尿病肾病的发生和发展。Objective:To investigate the expression and significance of fibrinogen-like protein-2 prothrombinase(Fgl-2) in renal tissue of diabetic rats(DM).Method:The rats were randomly divided into control group and diabetic group.The model group was induced to type 2 diabetes by diets enriched with glucose and fat and intraperitoneal injection with streptozoticin(STZ).24 h urine protein,creatinine,urea nitrogen,profile of kidney hypertrophy(KW/BW)were determined respectively and the pathological changes in the renal tissue of rats were observed at 19th week,23rd week and 28th week of experiment.The renal tissue were examined by hematoxin eosin staining(HE),periodic acid schiff staining(PAS) and Masson's trichrom staining(MASSON) to observe the renal pathologic changes.The proportion of microembolization area to per unit renal glomerulus area was calculated.Renal expression of Fgl-2 prothrombinase was detected by RT-PCR and immunohistochemical method.Correlativity between the proportion of microembolization area to per unit renal glomerulus area and the expression of Fgl-2 prothrombinase protein was analyzed.Results:Comqared with those!of control group,the 24 h urine protein,creatinine,urea nitrogen,KW/BW and expression of Fgl-2 prothrombinase in renal tissue of type 2 diabetic rats were increased.Fgl-2 prothrombinase expression was detected in microvascular endothelial cell of renal glomerulus and renal interstitium.Typical morphological changes in the model included glomerular hypertrophy,mesangial expansion,thickening of glomerular basement membrane and microembolization in the renal tissue of type 2 diabetic group.The proportions of microembolization area to per unit renal glomerulus area of type 2 model group were higher than the normal group.Positive correlation was found between Fgl-2 prothrombinase expression and the proportion of microembolization area to per unit renal glomerulus area.Conclusion:The expression of Fgl-2 prothrombinase mRNA and protein was increased in renal tissue of DM rats;Fgl-2 prothrombinase m

关 键 词：2型糖尿病大鼠 肾脏损害 微血栓形成 凝血酶原 肾小管间质纤维化 酶介导 糖尿病肾病 肾小球滤过 

分 类 号：R349.64[医药卫生—基础医学] R544.1