他克莫司对肾缺血再灌注损伤大鼠肾组织MMP-2、MMP-9表达的影响

Effect of tacrolimus on the expression of MMP-2 and MMP-9 in rats with renal ischemia-reperfusion injury

目的探讨他克莫司对肾缺血再灌注损伤大鼠肾组织MMP-2、MMP-9表达的影响。方法选用Wistar大鼠60只,随机分为三组;假手术组、对照组实验组,每组20只。假手术组仅开腹、分离肾动脉,不阻断血流;对照组于缺血前6h经尾静脉注射生理盐水1mL;实验组于缺血前6h经尾静脉注射他克莫司(0.5mg/kg)。到达设定的不同灌注时间点采血及肾脏标本,测定血清肌酐(Ser)、血尿素氮(BUN);检测肾组织基质金属蛋白酶(MMP-2、MMP-9)表达;HE染色分析肾组织病理损伤程度。结果在再灌注2.6和24 h时,实验组的Ser、BUN水平显著低于对照组(P<0.05),在再灌注0.5、2 h时,实验组MMP-2、MMP-9的阳性表达细胞数较对照组明显减少,差异有统计学意义(P<0.05),而在再灌注6 h和24 h时,与同期假手术组比较,对照组的MMP-2、MMP-9的阳性表达细胞数增多,差异有统计学意义(P<0.05)。HE染色光镜下发现:对照组的肾小管及肾小管上皮细胞病变程度重;实验组的肾小管及肾小管上皮细胞病变程度明显减轻;假手术组肾小管及肾小管上皮细胞未见改变。结论他克莫司预处理可以减轻大鼠肾缺血再灌注损伤,其机制可能与抑制肾脏MMP-2、MMP-9蛋白的表达有关。

Objective To investigate tacrolimus on the expression of MMP-2 and MMP-9 in rats with renal ischemiareperfusion injury.Methods Sixty healthy Wistar rats were assigned randomly into three groups:sham operation,control group,experimental group,20 rats in each group.Sham operation group,only open abdominal,separation of renal artery,no blocking blood flow,control group,is chemia in the past 6 h from the end of intravenous injection of saline 1 mL,experimental group,ischemia in the past 6h from the end of intravenous injection of tacrolimus(0.5 mg/kg)were performed.Reperfusion at different points in time when the blood and kidney samples were removed from rats,serum creatinine(Scr),blood urea nitrogen(BUN)were determined by automatic biochemical analyzer.Detection of renal MMP-2,MMP-9 was detected by immunohistochemistry and kidney injury was analyzed with HE staining.Results In reperfusion 2,6 and 24 h,the experimental group of Scr,BUN level was significantly lower than the control group(P<0.05),Instead,MMP-2,MMP-9 positive expression cells,the experimental group and control group was statistically significant difference.In the 6 and 24 h reperfusion,MMP-2,MMP-9 positive expression of cells in the control group compared with the same period in sham-operated group,the difference was statistically significant.By the light microscope control group of renal tubular epithelial cells and the degree of emphasis on disease significantly serious.The experimental group of renal disease and renal epithelial cells reduced significantly.Sham group of tubular and tubular epithelial cells no obvious change.Conclusions Tacrolimus pretreatment can reduce renal ischemia-eperfusion injury,possibly through renal MMP-2,MMP-9 protein expression,lead to improvements in renal ischemia-reperfusion injury.