雷公藤多甙联合厄贝沙坦对糖尿病肾病大鼠足细胞nephrin和podocin表达的影响

目的 观察雷公藤多甙联合厄贝沙坦对糖尿病肾病大鼠足细胞nephrin和podocinmRNA和蛋白表达的影响.方法 将体重200 ～ 260 g的50只SD大鼠按随机数字表法分为正常对照组和4个模型组（n=10）,后者分别应用链脲佐菌素造模成功后分为糖尿病肾病组（DN组）、厄贝沙坦组、雷公藤多甙组和雷公藤多甙联合厄贝沙坦组.给予相应干预8周后,检测血尿指标,HE染色观察肾组织病理变化,逆转录-多聚酶链反应（RT-PCR）法检测各组大鼠肾皮质中nephrin和podocinmRNA和蛋白表达.结果 （1）与DN组大鼠比较,雷公藤多甙联合厄贝沙坦组大鼠肾皮质nephrin mRNA （0.507±0.024比0.276 ±0.015,P ＜0.01）和podocin mRNA （0.533±0.024比0.463±0.022,P＜0.01）表达上调.（2）与DN组大鼠比较,雷公藤多甙联合厄贝沙坦组大鼠肾皮质nephrin蛋白（0.738±0.029比0.199±0.012,P＜0.01）和podocin蛋白（0.811 ±0.032比0.227±0.014,P＜0.01）表达上调.（3） HE染色和Masson染色显示,糖尿病组大鼠肾脏肾小球体积增大,系膜基质弥漫增多,系膜细胞明显增多,基底膜弥漫增厚,间质可见灶性淋巴细胞及单核细胞浸润,厄贝沙坦组和雷公藤多甙组病变较糖尿病组减轻,雷公藤多甙联合厄贝沙坦组大鼠肾脏组织病变较厄贝沙坦组和雷公藤多甙组进一步减轻.结论 雷公藤多甙联合厄贝沙坦对糖尿病大鼠的肾脏足细胞具有保护作用,这种保护作用可能是通过上调足细胞nephrin和podocin mRNA和蛋白表达有关.

Effect of tripterygium combined irbesartan on nephrin and podocin expression in the podocyte of diabetic nephropathy rats

Objective To observe the effect of tripterygium and irbesartan on nephrin and podocin expression in the podocyte of diabetic nephropathy rats. Methods Fifty SD rats （weight 200-260 g） were randomly divided into control group（ group C） and model group. Rats in model group were then divided into diabetic nephropathy group （group DN）, Irbesartan group （ group I） , Tripterygium group （ group T） and combined treatment group（ group T ＋ I ） after being given streptozotoein （STZ） （60 mg/kg） by a single intraperitoneal injection to establish animal model of diabetes. After 8 weeks, blood and Urine index were measured. The renal cortical tissues were obtained and used for HE staining to determine pathological changes. The expression of nephrin and podoein in renal cortices were semiquantitatively measured with RT- PCR. Results Compared to group DN, the mRNA expressions of nephrin and podocin were higher in the cortex of renal in group （T ＋ I） compared to group DN （0. 507 ~ O. 024 vs 0. 276 ~ 0. 015, P 〈 0. O1 and 0. 533 ＋ O. 024 vs 0. 463 -＋ 0. 022, P 〈 0. O1 ）. The expressions of nephrin and podocin protein were higher in the cortex of renal in group （ T ＋ I） compared to group DN （ 0. 738 ＋ 0. 029 vs 0. 199 ＋ 0.012, P 〈 0. 01 and O. 811 _＋0. 032 vs 0. 227 ＋0. 014, P 〈0. 01 ）. HE and Masson staining showed that the glomerular volume became bigger, messegium increased, mesangial cells proliferation, basement - membrane thickening and lymphocytes and mononuclear cell infiltration in group DN, which reduced in Irbesartan group and Tripterygium group, and further reducing in combined treatment group. Conclusions Tripterygium combined irbesartan play a protective role on the podocytes in diabetic nephropathy rats. The mechanism may be partly through the up-regulated expression of nephrin and podocin in kidney.