【摘要】 目的 研究蛋白质精氨酸甲基转移1(PRMT1)-非对称性二甲基精氨酸(ADMA)- 二甲基精氨酸二甲胺水解酶1(DDAH1)代谢轴在糖尿病大鼠肾脏组织中的表达，观察替米沙坦是否干预其表达和对肾脏功能的影响。 方法 将30只大鼠随机分为正常对照组(NC组，n=10)和实验组(n=20)，实验组全部注射STZ后，造模成功后随机分为糖尿病组(DM组，n=10)和替米沙坦组(TM组，n=10)，8周后测定FPG(FBG)、血清尿素氮(BUN)、肌酐(Cr)、24小时尿白蛋白(24h Microalbuminuria)、一氧化氮(NO)和一氧化氮合酶(NOS)，用ELISA法测定肾脏组织中ADMA的含量;RT-PCR法检测肾脏组织中PRMT1及DDAH1的mRNA的表达;免疫组化及蛋白质印记技术的方法观察PRMT1在肾脏组织中的表达。 结果 与NC组比较，DM组肾脏组织中ADMA的浓度明显升高(314.70±40.85 versus 159.99±32.08 μmol/L; P<0.01)，经替米沙坦治疗后TM组显著低于DM组(237.25±23.93 versus 314.70±40.85 μmol/L);DM组与NC组比较，PRMT1、NO、NOS、BUN、Cr、24小时尿白蛋白均明显升高，DDAH1明显降低;经替米沙坦干预治疗8周后，ADMA及PRMT1降低，DDAH1、NOS及NO升高，肾功能明显改善。 结论 在糖尿病状态下，PRMT1- ADMA- DDAH1代谢轴表达异常,加剧了氧化应激,使肾脏功能下降,替米沙坦的干预增加了DDAH1，降低了PRMT1，从而降低ADMA的表达，在一定程度上减轻了氧化应激的损伤，保护了肾脏功能。

　　【关键词】糖尿病;氧化应激;肾脏;非对称二甲基精氨酸;替米沙坦

　　The effects of telmisartan on PRMT1-ADMA-DDAH1 metabolic axis expression in the kidney of type 2 diabetic rats MEI Xi,LIU Dong-fang, Wang Nan-nan,et al. Department of Endocrinology, the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China

　　Corresponding author: LIU Dong-fang. Email: ldf023023@163.com.cn

　　【Abstract】 Objective To explore the expression of PRMT1-ADMA-DDAH1 axis in kidney tissue of diabetic rats, and the effects of Telmisartan on this axis and the function of kidney. Methods Rats were respectively assigned to control group (NC, n=10), diabetes group (DM, n=10) and Telmisartan group (TM, n=10). Type 2 diabetes mellitus models were established in rats by injecting streptozotocin (30mg/Kg) intraperitoneally after feeding with the diets enriched with high-lipid and sucrose for 4 weeks. Telmisartan (TM) group was feeding with the diets enriched with high-lipid and sucrose and telmisartan (10mg/Kg). 8 weeks later, the content of ADMA in kidney tissue was measured by ELISA, the expression of PRMT1 was observed by immunohistochemistric and Western blot. The mRNA expression of PRMT1 and DDAH1 were determined by RT-PCR. Results The concentrations of ADMA were significantly elevated in the kidney of diabetic rats (314.70±40.85 versus 159.99±32.08 μmol/L; P<0.01), and were significantly reduced by telmisartan (237.25±23.93 versus 314.70±40.85 μmol/L; P<0.01).The mRNA expression and the average optical density of PRMT1 in DM group and TM group were much higher than those in NC group (P <0.01), however, the mRNA expression of DDAH1 was significantly decreased (P <0.01), After 8 weeks-treatment, the ADMA and PRMT1 were decreased, while DDAH1 and NO were increased, and the renal function was improved obviously. Conclusion The expression of the PRMT1-ADMA-DDHA1 axis in kidney tissue was abnormal in diabetes condition. Telmisartan increases the expression of DDAH1, decreases PRMT1 in renal, which leads to the lower ADMA and reduces the oxidative stress and protects the renal function.

　　【Key words】diabetes mellitus; oxidative stress; kidney; Asymmetric dimethylarginine,; Telmisartan