目的:观察维生素C(VitC)对大鼠肾脏缺血再灌注(RIR)基质金属蛋白酶-2(MMP-2)表达的影响,探讨其对RIR损伤保护的机制。方法:48只雄性大鼠随机分成假手术组、RIR组和VitC组,比色法测定各组血清尿素氮(BUN)、肌酐(Scr)水平及肾组织丙二醛(MDA)水平、超氧化物歧化酶(SOD)、乳酸脱氢酶(LDH)活性;HE染色观察肾组织病理变化情况,并进行中性粒细胞计数;免疫组化法观察肾组织MMP-2蛋白表达。结果:与RIR组比较,VitC组血清BUN,Scr水平,肾组织匀浆MDA,LDH水平以及中性粒细胞计数均显著下降,而SOD活性显著升高;肾组织病理切片镜下显示RIR组大量肾小管结构缺损,变性,出血,坏死,VitC组较RIR组肾小管病变减轻明显;VitC预处理后,MMP-2表达较RIR组肾小管显著减少。结论:肾脏缺血再灌注时,MMP-2参与介导了中性粒细胞对肾组织的浸润和自由基的活化,VitC可能通过降低MMP-2在肾组织中的表达而减轻肾脏缺血再灌注损伤。
Objective : To observe the changes of vitamin C (VitC) on the expression of MMP-2 in rat after renal isehemia reperfusion ( RIR ) injury in order to elucidate the mechanism of its protective effect. Methods: Forty eight SD male rats were randomly divided into 3 groups: the sham operated(sham) group, the RIR group and the VitC group. The level of serum creatinine (Scr) , blood urea nitrogen (BUN) , the activity of renal SOD, LDH, and the content of MDA were detected respectively. Pathological changes of kidney were investigated by HE staining, the number of neutrophil(N) was counted and the expression of MMP-2 in kidney was evaluated by immunohistoehemical method. Results: In comparison with RIR group, both the levels of Scr, BUN, MDA and the activity of LDH were significantly lower, as well as the number of N, while the activity of SOD was obviously higher in the VitC group. There were significant pathological changes in renal tissue in the RIR group, which degeneration, congestion and necrosis were found in many renal tubules, however, fewer injuries were found in the VitC group compared with RIR group; the expression of MMP-2 was significantly enhanced in renal tubules after RIR while it decreased dramatically in the VitC group. Conclusion: The adhesion of neutrophil to kidney and the activation of free radicals could be mediated by MMP-2, and VitC may alleviate renal ischemia reperfusion injury through decreasing the expression of MMP-2.