罗格列酮通过抑制肾组织MMP-9过表达而减轻糖尿病大鼠肾损害

Rosiglitazone attenuates renal injury in diabetic rats via inhibiting over-expression of matrix metalloproteinase-9 in the kidney

目的:观察罗格列酮是否抑制肾组织基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)过表达而减轻糖尿病大鼠肾损害。方法:糖尿病模型建立1周后,大鼠灌胃给予罗格列酮(5 mg.kg-1.d-1)或生理氯化钠溶液。在第8周,检测尿白蛋白(ALB)、尿视黄醇结合蛋白(RBP)和尿MMP-9排泄率以及外周血血糖;以电镜观察肾脏病理变化,并以逆转录PCR检测肾脏MMP-9mRNA表达。结果:糖尿病大鼠的血糖、尿ALB,RBP和MMP-9排泄水平均显著升高(P<0.01);罗格列酮显著降低尿ALB,RBP和MMP-9排泄率(P<0.01)。糖尿病大鼠肾脏MMP-9mRNA表达明显上调(P<0.01),而罗格列酮显著减低MMP-9 mRNA表达(P<0.01)。罗格列酮还明显减轻糖尿病大鼠的肾脏病理改变。结论:罗格列酮对大鼠糖尿病肾损害具有一定的保护作用,可能部分与其抑制肾脏MMP-9过表达有关,而不依赖其降血糖作用。

Objective： To determine whether rosiglitazone attenuates renal injury in diabetic rats via inhibiting over-expression of matrix metalloproteinase-9 （MMP-9） in the kidney. Methods： One week after induction of diabetes mellitus model, rats were treated with oral rosiglitazone （5 mg.mg·kg^-1·d^-1） or saline. The urinary excretion rates of albumin （ALB） , retinal-binding protein （RBP） and MMP-9 as well as blood glucose were determined at 8th week. The renal pathological changes were observed by electron microscopy and the expression of MMP-9 mRNA in renal tissue was detected by RT-PCR. Results： The urine excretion rates of ALB, RBP and MMP-9 as well as blood glucose were increased in diabetic rats （ P 〈 0.01 ）. The urine excretion rates of ALB, RBP and MMP-9 was significantly decreased by rosiglitazone （P 〈0.01 ）. The expression of MMP-9 mRNA in the kidney was markedly up-regulated in diabetic rats, and the increased expression was reduced by rosiglitazone （P 〈 0.01 ）. Moreover, rosiglitazone remarkably improved renal pathological changes in diabetic rats. Conclusion： Rosiglitazone has a protective effect on renal injury in diabetic rats, which may partly relate to inhibiting over-expression of MMP- 9, independently of its hypoglycemic effect.