血浆同型半胱氨酸对糖尿病肾损伤的影响  

The role of plasma homocysteine in diabetic kidney disease

作　　者：张晋卿[1] 贾汝汉[1] 赵胜豪[1] 王雷[1] 刘烨[1] 

机构地区：[1]武汉大学人民医院肾内科,武汉430060

出　　处：《临床肾脏病杂志》2009年第4期179-181,F0003,共4页Journal Of Clinical Nephrology

基　　金：武汉大学国家大学生创新实验项目（071048658）

摘　　要：目的观察血浆同型半胱氨酸水平与糖尿病肾脏病大鼠肾损伤的关系及替米沙坦对其影响。方法用链佐菌素（STZ）诱导糖尿病大鼠模型，成模18只后随机分为替米沙坦治疗组（A组）和实验对照组（B组），每组各9只；另设空白对照组（C组）10只。于12周末收集24h尿，测定尿白蛋白排泄率（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，免疫组化法测。肾组织中纤溶酶原激活物抑制物-1（PAI-1）的表达水平。结果①与C组相比，B组肾肥大指数（肾质量／体质量）、UAER显著增加（P〈0．05），血浆Hcy浓度明显升高（P〈0．01），肾组织表达PAI-1明显增强（P〈0．05）。②与B组相比，A组血浆Hcy水平明显下降（P〈0．05），肾组织表达PAI-1显著减少（P〈0．01），肾肥大指数、UAER显著降低（P〈0．01，P％0．05）。③相关性分析显示，血浆Hcy浓度与肾组织表达PAI-1水平呈显著正相关（r=0．641，P〈0．01），与UAER呈显著正相关（r=0．684，P〈0．01）。结论血浆Hcy参与糖尿病肾损伤的发生、发展，其机制可能与其引起纤溶系统失衡等因素有关；替米沙坦可通过减少PAI-1表达水平而降低血浆Hcy水平，恢复纤溶系统平衡，降低蛋白尿，保护肾功能。Objective To observe the level of homocysteine （Hcy） in the pathogenesis of diabetic kidney disease in rat, and the effect Telmisartan to it. Methods Diabetes was induced in male Sprague-Dawley（SD） rats （about 200 grams） by a single peritoneal injection of 60 nag kg-1 streptozotocin （STZ）. After beening induced, the rats were devided into the diabetic group and the treatment group randomly. Additionally, a normal control group was also established. After the success of modeling,animals were killed by cardiac venipuncture after 24 hour urine samples were collected in the end of the 12ed week. Plasma Hey was quantified using ELASE. Biochemical indicators such as serum glucose and ereatinine was measured by biochemical analyzer. Weighing the kidney tissue, the concentration of PAI-1 in renal cortex was analyzed by immunohistochemistry. Results Compared with normal control group rats, ① the Kidney hypertrophy index and UAER markedly increased（P〈0. 05） in diabetics rats. Plasma Hey level increased in diabetics rats（P〈0. 01 ）, meanwhile the concentrations of PAI-1 in nephridial,tissue is intensification. ②Compared with diabetic rats,Plasma Hcy level was positively decreased（P〈0. 05） and the PAI-1 concentration in the nephridial tissue was markedly reduced. ③Plasma Hcy level was positively correlated with the urinary protein concentration and the PAI-1 concentration in the nephridial tissue （r = 0. 641, r = 0. 684, P〈0. 01）. Conclusion These results indicate that the plasma Hey level played an important role in the occurrence and development of diabetic nephropathy. The mechanism is linked to Hcy-induced fibrolysis disequilibrium. Telmisartan can reduce the level of serum Hcy through cutting down the expresstion of PAI-1, restore the balance of the fibrinolytic system, reduce protein urea and protect kidney function.

关 键 词：半胱氨酸 纤溶酶原激活物抑制物-1 糖尿病肾脏病 

分 类 号：R587.1[医药卫生—内分泌] R692[医药卫生—内科学]