辛伐他汀对糖尿病大鼠MMP-9表达的影响及对肾脏保护的研究

Effects of simvastatin on the renal injury of diabetic rats and renal expression of matrix metalloproteinase-9

目的观察辛伐他汀对糖尿病大鼠肾脏的保护作用及其对肾组织基质金属蛋白酶-9(MMP-9)mRNA表达和尿MMP-9排泄的影响。方法将Wistar大鼠随机分为正常对照组、糖尿病组、辛伐他汀治疗组。检测各组第8周血糖、HbA1c、12 h尿视黄醇结合蛋白(RBP)、尿白蛋白(al-bumin,ALB)和尿MMP-9排泄率,第8周留取肾脏标本做电镜观察及采用逆转录PCR(RT-PCR)检测MMP-9mRNA。结果①第8周,糖尿病组及辛伐他汀治疗组尿ALB、RBP、MMP-9排泄率均高于正常对照组(P<0.01),辛伐他汀治疗组较糖尿病组有明显减少(P<0.01);尿MMP-9排泄率与尿ALB和RBP排泄率呈正相关关系。②第8周,与正常对照组相比,糖尿病组大鼠肾脏MMP-9mRNA表达明显上调(P<0.01),而辛伐他汀治疗组MMP-9mRNA表达则较糖尿病组明显下降(P<0.01)。电镜下辛伐他汀治疗组肾脏病理改变较糖尿病组明显减轻,同正常对照组相比仅有少量病变。结论辛伐他汀对糖尿病大鼠具有确切的肾脏保护作用,部分与其抑制肾脏MMP-9过度表达有关。

Objective To observe the effects of simvastatin on the expression of matrix metalloproteinase-9 （MMP-9） mRNA in renal tissue and urinary MMP-9 excretion of diabetic rats and find its renal protective mechanisms. Methods 24 Wistar rats were randomly divided into control, diabetic, simvastatin treament groups. Peripheral blood glucose, HbAlc, the urinary albumin （ ALB）, retinal-binding protein （RBP） and MMP-9 were tested at 8th week. The renal tissue of rats were obtained for renal pathological changes by electron micro- scope and RT-PCR to examine the expression of MMP-9. Results （1）At the 8th week, the urine excretion rates of ALB, RBP and MMP-9 in diabetic and simvastatin treament groups were higher than those in control group （P 〈0.01 ）. In simvastatin treament group, they were de- creased significantly than those in diabetic group （P 〈0.01 ）. Urinary MMP-9 level was positive correlated with the urinary ALB and RBP levels. （2）The expression of MMP-9 mRNA was markedly up-regulated in diabetic group compared with that in control group, which in simvastatin treament group was much lower than that in diabetic group （P 〈 0. 01 ）, the renal pathological changes in simvastatin treament group were much lighter than those of diabetic group, but a little heavier than those of control group. Conclusions Simvastatin has a renal-protection effect, which may be associated partly with down-regulated over-expression of renal tissue MMP-9.