洛沙坦对人类正常系膜细胞及糖尿病肾病大鼠肾脏组织环氧化酶2的影响(英文)  

Effect of losartan on cyclooxygenase-2 expression in normal human mesangial cells and kidneys of rats with diabetic nephropathy

作　　者：周巧玲[1] 彭卫生[1] 保元裕一郎[2] 刘志纯[1] 杨敬华[1] 

机构地区：[1]中南大学湘雅医院肾内科,长沙410008 [2]日本鹿儿岛大学医学部第二内科

出　　处：《中南大学学报（医学版）》2008年第9期790-799,共10页Journal of Central South University ：Medical Science

摘　　要：目的:观察高糖及洛沙坦对正常人类系膜细胞(NHMCs)增殖及环氧化酶表达的影响,及洛沙坦对糖尿病肾病(DN)大鼠肾脏环氧化酶(COX2)及转化生长因子β1(TGF-β1)的影响。方法:体外实验采用高糖培养NHMCs,分二组(洛沙坦组,非干预组),用WST-1法检测NHMCs增殖,Western印迹和RT-PCR检测COX2表达。体内实验采用链脲菌素方法制备DN大鼠模型,洛沙坦干预4周后,分别检测大鼠肾脏病理改变、尿血栓素B2(TXB2)、24 h尿蛋白定量,同时采用免疫组织化学及RT-PCR方法检测大鼠肾脏COX2及TGF-β1表达。结果:洛沙坦呈剂量依赖性地抑制高糖引起的NHMCs增殖,同时还能减少高糖及低糖引起的NHMCs的COX2高表达;体内实验中,DN大鼠组肾体质量指数、尿TXB2和24 h尿蛋白均较正常对照组明显升高,洛沙坦能减少DN大鼠肾体质量指数、尿TXB2、24小时尿蛋白,同时显著抑制肾组织COX2和TGF-β1表达。结论:洛沙坦能减少NHMCs的COX2表达,在高糖条件下更为明显。洛沙坦能抑制DN大鼠肾组织COX2和TGF-β1表达,从而改善DN肾损害。Objective To investigate the effect of high glucose and losartan on cell proliferation and cyelooxygenase-2 （COX2） expression in normal human mesangial cells （NHMCs） , and to examine the effect of losartan on COX2 and transforming growth factor-betal （TGF-β1） expression in a model of diabetic nephropathy （DN）. Methods NHMCs were cultured in vitro in high glucose media with or without losartan. NHMCs proliferation and COX2 expression were determined by WST-1, Western blot, and RT-PCR. The rat model of DN was produced by injections of streptozocin （STZ）. After the treatment with losartan for 4 weeks, glomernlar hypertrophy, urinary thromboxane B2 （ TXB2 ） and 24 h urinary protein counts were measured, and COX2 and TGF-β1 expressions were investigated using immunohistoehemieal techniques and RT-PCR. Results Losartan dose-dependently inhibited the proliferation of NHMCs in response to high glucose. Losartan also decreased COX2 expression in NHMCs at high or low glucose concentrations. In vivo experiments found kidney weight/body weight （KW/BW） , urinary TXB2 and 24 h urinary protein counts increased significantly in the DN group. Losartan reduced KW/BW, urinary TXB2 , and 24 h urinary protein counts and significantly suppressed the over-expression of COX2 and TGF-β1. Conclusion Losartan reduces COX2 expression in NHMCs, especially at high glucose concentrations. Losartan could suppress the expression of COX2. and TGF-β1 in the kidney of DN rats and attenuate the renal lesions caused by DN.

关 键 词：环氧化酶 人类正常系膜细胞 糖尿病肾病 洛沙坦 

分 类 号：R587.2[医药卫生—内分泌]