摘要
目的 观察环加氧酶 -2 (COX -2 )在 2型糖尿病大鼠肾脏表达并探讨COX -2选择性抑制剂莫比可 (Mobic)对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)、前列腺素代谢产物血栓烷素B2 (TXB2 )、6-酮前列腺素F1α( 6-Ket -PGF1α)及肾脏结构、功能的影响。方法 将实验大鼠 18只随机分成正常对照组 (C组 )、糖尿病组 (D组 )、Mobic治疗组(M组 )。模型复制成功后 6周末用免疫组织化学法检测肾脏COX -2、MMP -9、TIMP -1表达 ,采用放射免疫法测定尿液TXB2 、6-Ket-PGF1α排泄量。结 D组大鼠出现肾脏基底膜增厚、系膜外基质增多、COX -2、TIMP -1表达增强 ,MMP -9表达减弱及尿白蛋白、TXB2 、6-Ket -PGF1α排泄量增加等改变 ;M组肾脏基底膜增厚、系膜外基质增多现象及COX -2、TIMP -1表达较D组减弱、MMP-9表达增强 ,尿TXB2 、6-Ket -PGF1α排泄量较D组明显下降且无明显蛋白尿发生。结论 COX -2参与了糖尿病肾病发生、发展病理过程。Mobic通过抑制COX -2活性、减少前列腺素合成、调节MMP -9/TIMP -1合成发挥其降低蛋白尿。
Objective To observe the renal expression of cyclooxygenase-2 (COX-2) in rats with type 2 diabetes, and explore the effect of selective COX-2 inhibitor Mobic on the expression of renal COX-2, matrix metalloproteinase-9(MMP-9), tissue inhibitor of matrix metalloproteinase-1(TIMP-1), TXB 2 and 6-Ket-PGF1α, as well as renal structure and function. Methods All rats were divided into control group, diabetes mellitus group and treatment group. Type 2 diabetic rats were treated with Mobic and vehicle respectively. Immunohistochemistry was used to detect the expression of COX-2,MMP-9 and TIMP-1 in renal tissues. The urinary TXB 2 and 6-Ket-PGF1α concentration was determined by radioimmunoassay at 6th week. Results There were an increasing expression of COX-2, TIMP-1 and decreasing MMP-9 expression in the renal tissue of type 2 diabetic rats. Mobic could increase MMP-9 expression and depress TIMP-1 expression througth inhibiting the expression of COX-2 in the renal tissues of type 2 diabetic rats. Conclusion COX-2 was involved in the pathogenesis of type 2 diabetic nephropathy. Selective COX-2 inhibitor Mobic might exert its renoprotective effects through inhibiting COX-2 activity, decreasing prostagladins systhesis, and modulating MMP-9 and TIMP-1 expression.
出处
《中国医师杂志》
CAS
2004年第6期777-779,共3页
Journal of Chinese Physician
