厄贝沙坦对2型糖尿病大鼠肾组织中核因子-κB和MMP-9/TIMP-1表达的影响  

Effect of irbesatan on the expressions of nuclear factor-kappa B and MMP-9/TIMP-1 in the renal tissue of rats with type 2 diabetes

作　　者：李华[1] 许传文[1] 吴扬[1] 徐艳梅[1] 黄丽红[1] 周立霞[1] 段小红[1] 苏春媚[1] 

机构地区：[1]武汉市普爱医院肾内科,430030

出　　处：《实用医学杂志》2008年第24期4197-4200,共4页The Journal of Practical Medicine

摘　　要：目的:观察2型糖尿病大鼠模型肾组织中核因子-κB(NF-κB)、基质金属蛋白酶-9(MMP-9)及基质金属蛋白酶组织抑制物-1(TIMP-1)的表达,并探讨血管紧张素Ⅱ受体拮抗剂厄贝沙坦对NF-κB、MMP-9、TIMP-1及肾脏结构与功能的影响。方法:将24只雄性Wistar大鼠随机分成正常对照组(A组)8只、模型组16只,应用高糖高脂加小剂量链脲佐菌素方法制备2型糖尿病大鼠模型,造模成功后模型组再分为糖尿病组(B组)8只和厄贝沙坦治疗组(C组)8只。6周后采用免疫组织化学及RT-PCR法检测各组大鼠肾脏组织中MMP-9、TIMP-1及NF-κBp65 mRNA的表达,观察肾脏结构和功能的变化。结果:(1)B组大鼠肾组织中NF-κB、TIMP-1的表达较A组和C组明显增强,C组表达强度介于A组和B组之间;MMP-9的表达情况则与之相反。(2)与A组和C组相比,B组肾小球基底膜明显增厚,系膜外基质及尿蛋白排泄率明显增多,C组的病理变化则较B组有所减轻。结论:NF-κB、MMP-9、TIMP-1参与了2型糖尿病肾病的发生、发展病理过程。厄贝沙坦通过抑制NF-κB活性、上调MMP-9、下调TIMP-1发挥其降低蛋白尿、延缓肾脏病理改变发生等治疗作用。Objective To observe the expressions of nuclear factor-kappa B （NF-κB）, matrix metalloproteinase-9 （MMP-9）, and tissue inhibitor of matrix metalloproteinase-1 （TIMP-1） in tbe renal tissue of rats with type 2 diabetes and investigate the effect of ATI receptor antagonist irbesatan on the expressions of NF-κB, MMP-9, and TIMP-1 along with renal structure and function. Methods The murine model of type 2 diabetes was established by the use of STZ at a small dose. 24 rats were randomized to control group （group A）, diabetes group （group B） or irbesatan group （group C）, 8 for each group. Immunohistochemistry and RT-PCR were used to detect the expressions of MMP-9, TIMP-1, and NF-κBp65 mRNA. Changes in renal structure and function were observed. Results The expressions of NF-κB and TIMP-1 were obviously upregulated but MMP-9 expression was downregulated in group B as compared with group A or C. The glomerular basement membrane was evidently thickened and extramesangial matrix and UAE were markedly increased in group B in comparison with group A or C while the pathological changes were less in group C than in group B. Conclusions NF-κB, MMP-9, and TIMP-1 are involved in the pathogenesis and development of diabetic nephropathy. Irbesatan plays a role in reducing proteinuria and delaying the occurrence of pathological changes in the kidney through inhibiting NF-κB activity, upregulating MMP-9 expression, and downregulating TIMP-1 expression.

关 键 词：糖尿病 2型 NF-κB 明胶酶B 基质金属蛋白酶组织抑制物-1 厄贝沙坦 

分 类 号：R96[医药卫生—药理学] R587.2[医药卫生—药学]