GLP-1对1型糖尿病大鼠肾脏AdipoR1和MCP-1表达的影响

Effects of GLP-1 on the expression of Adiponectin receptor 1 and MCP-1 in kidney of type 1 diabetic rats

目的观察胰升糖素样肽-1(GLP-1)受体激动剂艾塞那肽对1型糖尿病大鼠肾脏组织脂联素受体1(adipoR1)和单核细胞趋化蛋白-1(MCP-1)表达的影响,探讨艾塞那肽对1型糖尿病大鼠肾脏保护作用及机制。方法 30只雄性SD大鼠,随机分为健康对照组(A组,7只)和糖尿病造模组(23只)。采用链脲佐菌素(STZ)诱导1型糖尿病大鼠模型,共有19只大鼠造模成功。将造模成功的糖尿病大鼠随机分为糖尿病组(B组,10只)和艾塞那肽治疗组(C组,9只)。C组予以艾塞那肽10μg/(kg·d)皮下注射治疗8周。用实时荧光定量PCR方法测定大鼠肾脏组织Adipo R1和MCP-1 mRNA的表达,用免疫组织化学染色法检测Adipo R1在肾脏组织中的分布及表达,用酶联免疫吸附法(ELISA)测定血浆脂联素水平。结果与A组比较,B组糖尿病大鼠血糖、血脂、血肌酐、尿素氮、尿白蛋白排泄率、肾脏指数、肾脏组织Adipo R1 mRNA和蛋白表达以及MCP-1 mRNA表达均显著升高(P<0.05),而血浆脂联素水平显著降低(P<0.05)。经艾塞那肽干预后,C组大鼠血浆脂联素水平较B组显著升高(P<0.05),血脂、血肌酐、尿素氮、尿白蛋白排泄率、肾脏指数、肾脏组织Adipo R1 mRNA和蛋白表达以及MCP-1 mRNA表达较B组显著降低(P<0.05),而血糖无明显变化(P>0.05)。结论艾塞那肽可能通过上调1型糖尿病大鼠血浆脂联素水平和下调肾脏组织AdipoR1和MCP-1表达,抑制免疫炎症反应,改善肾功能及减轻肾脏病理损害,产生肾脏保护作用。

[Objective] To observe the effects of glucagon-like peptide-1 （GLP-1） receptor agonist exenatide on the expression of renal adiponectin receptor 1 （Adipo R1） and monocyte chemotactic protein 1 （MCP-1） in type 1 diabetic rats and to explore the protective roles and mechanisms of exenatide on kidney of type 1 diabet- ic rats. [Methods] Thirty male Sprague-Dawley （SD） rats were randomly divided into control （group A, n =7） and diabetic model （n =23） Type 1 diabetic： model was established by intraperitoneal injection of streptozotocin. There were 19 rats induced successfully to be diabetic. Diabetic rats were randomly divided into diabetic control （group B, n =10） and diabetic treated with exenatide （group C, n =9）. Rats in group C were injected subcuta- neously with exenatide in dose of 10 g·kg^-1·d^-1 for eight weeks. The mRNA expressions of renal Adipo R1 and MCP-1 were measured by real-time fluorescence quantitative PCR. The distribution and expression of Adipo RI in renal tissue were detected by immunohistochemical staining. Plasma adiponectin levels were detected by enzyme-Linked immunosorbnent assay （ELISA）. [Results] The levels of blood glucose, lipid, creatinine, and urea nitrogen, the albumin excretion rate, kidney index, the protein and mRNA expressions of renal Adipo R1 and the mRNA expression of renal MCP-1 were significantly increased in group B than those in group A （P 〈0.05）. The level of plasma adiponectin was significantly decreased in group B than that in group A （P 〈 0.05）. After exenatide treatment, the level of plasma adiponectin was significantly increased in group C than that in group B. The blood lipid, creatinine and urea nitrogen, the albumin excretion rate, kidney index and the expression of renal Adipo R1 and MCP-1 were significantly decreased in group C than that in group B （P〈0.05）. There was no difference in blood glucose between group B and group C. [Conclusion] Exenatide may produce renal protective roles by up-regulating the level of plasma adiponectin, down-regulating the ex- pression of renal AdipoR1 and MCP-1, which may result in the suppression of the inflammatory response, the improvement of renal funetion and the alleviation of pathologieal damage in diabetic rats.