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罗格列酮通过抑制肾脏基质金属蛋白酶-9 的表达来保护糖尿病大鼠免受肾损伤。

Rosiglitazone protects diabetic rats against kidney injury through the suppression of renal matrix metalloproteinase-9 expression.

出版信息

Diabetes Obes Metab. 2009 May;11(5):519-22. doi: 10.1111/j.1463-1326.2008.00990.x. Epub 2009 Feb 18.

Abstract

In this study, the effects of rosiglitazone on renal matrix metalloproteinase-9 (MMP-9) expression and its possible renoprotective mechanisms were investigated in streptozotocin-induced diabetic rats. We examined the urinary excretion rates of albumin (ALB), retinal-binding protein (RBP) and MMP-9 in control healthy rats (group C, n = 8), untreated diabetic rats (group D, n = 8) and diabetic rats treated with rosiglitazone (5mg/kg/day) (group R, n = 8) at eighth week. The renal tissue of diabetic rats was obtained for observing renal pathological changes by electron microscope and examining the expression of renal MMP-9 mRNA by RT-PCR. Our results showed that urinary excretion rates of MMP-9. ALB and RBP were significantly increased concurrently with the expression of renal MMP-9mRNA in group D compared with those of group C. Rosiglitazone significantly reduced urinary excretion rates of ALB, RBP and MMP-9 as well as the expression of renal MMP-9 mRNA. In addition, urinary excretion rate of MMP-9 showed positive relationship with urinary excretion rates of ALB and RBP. In conclusion, rosiglitazone definitely protects diabetic rats against renal injury, which may be partly associated with decreasing expression of renal MMP-9 mRNA and urinary MMP-9 production.

摘要

在这项研究中,我们研究了罗格列酮对链脲佐菌素诱导的糖尿病大鼠肾脏基质金属蛋白酶-9(MMP-9)表达的影响及其可能的肾脏保护机制。我们检测了对照组健康大鼠(C 组,n = 8)、未治疗的糖尿病大鼠(D 组,n = 8)和用罗格列酮(5mg/kg/天)治疗的糖尿病大鼠(R 组,n = 8)在第 8 周时的尿液白蛋白(ALB)、视网膜结合蛋白(RBP)和 MMP-9 的排泄率。我们还通过电镜观察糖尿病大鼠的肾脏组织病理学变化,通过 RT-PCR 检测肾脏 MMP-9mRNA 的表达。结果显示,与 C 组相比,D 组大鼠的 MMP-9、ALB 和 RBP 的尿液排泄率及其肾脏 MMP-9mRNA 的表达均显著升高。罗格列酮可显著降低 ALB、RBP 和 MMP-9 的尿液排泄率以及肾脏 MMP-9mRNA 的表达。此外,MMP-9 的尿液排泄率与 ALB 和 RBP 的尿液排泄率呈正相关。综上所述,罗格列酮确实能保护糖尿病大鼠免受肾脏损伤,这可能与降低肾脏 MMP-9mRNA 的表达和 MMP-9 的产生有关。

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