厄贝沙坦对2型糖尿病大鼠肾脏组织环加氧酶-2表达的影响

目的 探讨血管紧张素Ⅱ（AngⅡ）1型受体拮抗剂（ARB）厄贝沙坦对2型糖尿病大鼠肾组织环氧化酶-2（COX-2）表达的影响及其肾保护的可能机制.方法 将18只实验大鼠随机分成正常对照组（A组）、糖尿病组（B组）、厄贝沙坦治疗组（C组）.6周时用免疫组织化学法检测肾脏COX-2、基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶组织抑制物1（TIMP-1）表达,并采用放射免疫法测定尿液前列腺素代谢产物血栓烷素B2（TXB2）、6-酮前列腺素F1α（6-Ket-PGF1α）排泄量.结果 与A组比较,B组大鼠肾脏COX-2、TIMP-1表达明显增强,MMP-9表达减弱（COX-2：0.39±0.02 vs 0.24±0.04,TIMP：0.41±0.03 vs 0.24±0.02,MMP-9：0.24±0.02 vs 0.32±0.02,P＜0.05）;与B组比较,C组COX-2（0.31±0.03）、TIMP-1（0.34±0.02）表达减弱、而MMP-9（0.29±0.03）表达增强（P＜0.05）;B组大鼠尿TXB2（1313.10±14.03）ng/d]、6-Ket-PGF1α（1598.00±39.25）ng/d]排泄量明显增加;C组尿TXB2（658±13.68）ng/d]、6-Ket-PGF1α（1022±58.04）ng/d]排泄量则较B组明显下降;B组大鼠出现明显蛋白尿及基底膜增厚、系膜外基质增多等病理变化;C组则无明显蛋白尿且病理变化较B组明显减弱.结论 COX-2参与了糖尿病肾病发生、发展病理过程;厄贝沙坦抑制COX-2活性、上调MMP-9、下调TIMP-1是其肾保护的可能机制之一.

Effect of irbesartan on clyclooxygenase-2 expression in experimental type 2 diabetic rat

Objective To investigate the effect of angiotensin Ⅱ (AngⅡ) type 1 receptor block irbesartan on the expression of renal cyclooxygenase-2 ( COX-2 ) in rats with type 2 diabetes mellitus.Methods 18 rats were divided into control group, diabetes mellitus group and treating group.Immunohistochemistry was used to measure the expression of COX-2, matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1).The urinary TXB2,6-Ket-PGF1 αconcentration was determined by radioimmunoassay at the 6th week .Results There was an increasing expression of COX-2,TIMP-1 and decreasing M MP-9 ( COX-2:0.39 ± 0.02 vs 0.24 ± 0.04, TIMP :0.41 ± 0.03 vs 0.24 ± 0.02,MMP-9:0.24 ± 0.02 vs 0.32 ± 0.02, P ＜ 0.05 ) expression in the diabetes mellitus group ( P ＜ 0.05 ).Irbesartan could increase MMP-9 (0.29 ± 0.03 ) and depress TIMP-1 (0.34 ± 0.02) expression through inhibiting the expression of COX-2(0.31 ± 0.03) in renal tissue.Conclusions COX-2 was involved in the pathogenesis of the injury of type 2 diabetic nephropathy.Irbesartan might exert its renoprotective effects through inhibiting COX-2 activity, modulating the expression of MMP-9 and TIMP-1.