摘要
目的:探讨特异性环氧化酶(COX)-2抑制剂rofecoxib对MRL/lpr小鼠狼疮性肾炎的治疗作用及其机制。方法:将12只3月龄MRL/lpr自发狼疮小鼠随机均分为rofecoxib组和无药物干预的对照组,rofecoxib组予以rofecoxib 10 mg.kg-1.d-1。12周后分别测定各组小鼠尿蛋白排泄量、血肌酐水平;放射免疫法测定血清抗ds-DNA抗体结合率、AngⅡ,尿TXB2、6-Ket-F1α的变化;肾组织病理学检查及免疫组化测定肾组织COX-2、TGF-β1蛋白的表达。结果:12周后,rofecoxib组尿蛋白排泄量、血肌酐水平降低(P<0.05);肾小球细胞外基质明显减少(P<0.05);免疫组化结果表明,rofecoxib组肾组织内COX-2、TGF-β1表达较对照组减少(P<0.05)。rofecoxib组尿TXB2及血AngⅡ水平较对照组明显降低(P<0.05),但两组血清抗ds-DNA抗体结合率和尿6-Ket-F la水平均无显著性差异(P>0.05)。结论:COX-2抑制剂对自发狼疮小鼠肾损害有良好的治疗作用,能减少细胞外基质的聚积,降低蛋白尿,稳定肾功能,具有保护肾脏的作用。
Objective To observe the therapeutical effect and explore the underlying molecular mechamisms of specific cyclooxygenase-2 inhibitor（rofecoxib） on MRL/lpr mice. Methods 12-week female MRL/lpr mice were randomly assigned into following groups： the rofecoxib（ 10 mg · kg^-1 · d^-1） for 12 weeks and the control group. Suppressive effect of the drugs on conjugate rate of serum anti-dsDNA antibody, serum angiotensin Ⅱ , thromboxanc B2 and 6- keton-prostaglandin-F1α evels were determined by using radio-immunological assay. The changes of proteinuria, serum creatinine and pathology in renal were also observed. Immunohistochemistry was used to examine the expression of TGF-β1 and COX-2 in the kidney of MRL/lpr mice. Results Compared to the ones in the control group, mice treated with rofeeoxib had lower levels of proteinuria （P 〈 0.05 ） , serum creatinine（ P 〈 0.05 ） , the extraeellular matrix reduced significantly（ P 〈 0. 05 ） , the expression of the positive of TGF-β1 and COX-2 in renal tissue significantly decreased. Compared to the ones in the control group, mice treated with rofecoxib had lower levels of serum angiotensin Ⅱ and thromboxanc B2 （P 〈 0.05） , while the levels of 6-keton-prostaglandin-F1α, conjugate rate of serum anti-dsDNA antibody did not change （ P 〉 0.05 ）. Conclusions Rofecoxib reduces proteinuria and relieves renal injuries in lupus MRL/lpr mice. This protective effect might be explained by its immunosuppressive action, which leads to reduced expression of TGF-β1 and COX-2 in the kidney of MRL/lpr mice, decreases the deposition of extracellular matrix. Specific COX-2 inhibitor has a renoprotective effect on MRL-lpr/lpr mice.
出处
《东南大学学报（医学版）》
CAS
2006年第4期278-281,共4页
Journal of Southeast University(Medical Science Edition)
