血浆同型半胱氨酸对糖尿病肾脏损伤机制的探讨  

The Role of Plasma Homocysteine in Diabetic Renal Injury

作　　者：张晋卿[1] 贾汝汉[1] 赵胜豪[1] 王雷[1] 

机构地区：[1]武汉大学人民医院,湖北武汉430060

出　　处：《中国微循环》2009年第5期381-384,F0003,共5页Journal of Chinese Microcirculation

基　　金：武汉大学国家大学生创新实验项目(071048658#)

摘　　要：目的探讨血浆同型半胱氨酸水平与糖尿病肾脏病大鼠肾组织表达PAI-1的关系,并探讨其引起肾损伤可能的机制。方法38只健康SD雄性大鼠随机分为正常对照组及糖尿病组。用链佐菌素(STZ)诱导糖尿病大鼠模型,于第4、8、12周末收集24h尿测定UAER,并处死大鼠,心脏采血,ELISA法测血浆同型半胱氨酸(Hcy)水平,生化分析仪测血糖、血肌酐等生化指标。取肾脏称重,免疫组织化学法测肾组织中PAI-1的表达情况。结果与正常对照组相比,①糖尿病组大鼠肾肥大指数(肾质量/体质量,KW/BW)、UAER显著增加(P<0.05);②糖尿病组大鼠血浆Hcy浓度明显升高(P<0.01),且随病程延长而逐渐增加,肾组织表达PAI-1明显增强(P<0.05);③相关分析表明,血浆Hcy水平与肾组织表达PAI-1强度及UAER呈显著正相关(r=0.641,r=0.684,P<0.01)。结论血浆Hcy参与了糖尿病肾损伤的发生、发展,其机制可能与其造成内皮损伤,引起纤溶系统失衡等因素有关。Objective To observe the role of homocysteine （Hcy） in the pathogenesis of diabetic renal injury in rat and explore effect of Hcy to the plasminogen activator inhibitor-1 （PAI-1）. Methods Diabetes was induced in male Sprague-Dawley（SD） rats （about 200 grams） by a single peritoneal injection of 60 mg kg^-1 streptozotoein （STZ）. Animals with blood glucose levels higher than 16.7 mmol. L^-1 72 h after STZ injection were included in the study. Similar weight rats receiving a single dose of citrate buffer were served as controls. Animals were killed by cardiac venipuncture at the end of the 4th, 8th and 12th week. Plasma Hcy was quantified using ELASE, serum glucose, protein, creatinine were measured by biochemical analyzer, and urinary protein determinations were carried out spectrophotometrically. The concentration of PAI-1 in renal cortex was analyzed by immunohistochemistry. Results Compared with diabetic rats, （1） the kidney hypertrophy index （kw/bw） and UAER markedly increased （ P 〈 0.05） in diabetics rats. （2） Plasma Hcy level increased in diabetics rats （ P 〈0.01） and the tendency of increase is obvious with the extension of the course; meanwhile the concentrations of PAI-1 in nephridial tissue is intensified. （3） Plasma Hcy level was positively corre- lated with the urinary protein concentration and the PAI-1 concentration in the nephridial tissue （ r =0.641, r = 0. 684, P 〈 0.01）. Conclusion The plasma Hcy level plays an important role in the development of diabetic nephropathy. The mechanisms is related to Hcy-induced endothelium dysfunction and fibrolysis disequilibrium.

关 键 词：同型半胱氨酸 纤溶酶原激活物抑制物 糖尿病肾损伤 

分 类 号：R587.11[医药卫生—内分泌] R322.6[医药卫生—内科学]