厄贝沙坦对血管生成素样蛋白2在糖尿病大鼠肾脏表达的影响  

The effect of irbesartan on the expression of angiopoietin-like protein 2 in the kidneys of type 2 diabetes rats

作　　者：王艳[1] 李柯桢 宋起[1] 周丽敏[1] 栾健[3] 

机构地区：[1]青岛大学附属医院肾内科,266003 [2]青岛市第三人民医院血透室 [3]青岛市市立医院内分泌科

出　　处：《中华肾脏病杂志》2014年第8期609-613,共5页Chinese Journal of Nephrology

基　　金：青岛市科技局课题（2012-1-3-1-19-nsh）

摘　　要：目的通过观察厄贝沙坦对糖尿病大鼠血管生成素样蛋白2（ANGPTL2）表达的影响，探讨其主要的作用机制。方法60只雄性SD大鼠随机分为正常对照组（NC，15只）和实验组（45只）。实验组予高糖高脂喂养联合小剂量链脲菌素（STZ，30mg／kg）建立2型糖尿病（T2DM）大鼠模型，成功的模型（36只）再随机分为2组：糖尿病组（DM，18只）及厄贝沙坦组（DI，18只）。分别检测4周、8周及12周测体质量、血压、肾质量、血糖、血肌酐（Scr）、尿素氮（BUN），24h尿蛋白（UAL）的排泄量，镜下观察肾组织病理改变，免疫组化染色技术、实时定量PCR及Western印迹法检测肾组织ANGPTL2 mRNA及蛋白表达。结果DM组24h尿白蛋白量、三酰甘油、胆固醇、BUN及Scr在4周、8周及12周逐渐升高，且均高于同时间的NC组，差异有统计学意义（均P＜0．05）。DI组以上述指标均低于同时间的DM组，差异有统计学意义（均P＜0．05）。DM组4周、8周及12周的肾脏病理改变逐渐加重，同时间的DI组肾脏病理改变较DM组轻，但仍重于NC组。DM组4周、8周及12周肾脏中的ANGPTL2mRNA及蛋白的表达较NC组明显升高（均P＜0．05），DI组ANGPTL2的表达量低于同一时间的DM组，差异有统计学意义（P＜0．05）。结论ANGPTL2在糖尿病大鼠肾脏的表达量逐渐升高，而厄贝沙坦可降低ANGPTL2在肾的表达，保肾脏。Objective To observe the effect of irbesartan on the expression of angiopoietinlike protein 2 （ANGPTL2） in the diabetic rats kidney and explore the underlying mechanism. Methods A total of sixty male SD rats were divided into normal control group （NC group, n=15） and experimental group （n=45） randomly. The experimental group was fed with high sugar-fat diet and given a low dose streptozoein （STZ 30 mg/kg）to establish type 2 diabetic model. Rats successfully induced diabetes were randomly divided into 2 groups： diabetes group （DM） and irbesartan group （DI）. Weight, blood pressure, blood glucose, serum creatinine （Scr）, blood urea nitrogen（BUN）, 24 hour urinary albumin（UAL） and renal histomorphology were observed after drug intervention at the 4^th, 8th and 12^th weeks. The expression of ANGPTL2 in renal tissue were detected by immunohistochemistry, real-time PCR and Western blotting. Results The levels of Scr, BUN, TG, TC and UAL in group DM were higher than in group NC at the 4^th, 8^th and 12^th week （all P〈 0.05）. Compared with that in group DM,above indexes were lower in group DI at the 4^th, 8^th and 12^th week （all P〈0.05）. The pathological changes of the kidney in group DM were more serious than that in group DI. The expression of ANGPTL2 in group DM was much higher than that in group NC at the 4^th, 8^th and 12^th week （all P〈0.05）, and irbesartan treatment inhibited the up-regulation of ANGPTL2 in group DI（all P 〈0.05）. Conclusion The expression of ANGPTL2 increases in T2DM rats kidney tissue with time and irbesartan can inhibit the up-regulation of ANGPTL2 in T2DM rats.

关 键 词：糖尿病 肾病 血管生成素样蛋白2 厄贝沙坦 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]