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目的 :探讨丹参对肾缺血再灌注损伤保护效应的分子机制。 方法 :以大鼠缺血再灌注肾损伤为模型 ,采用组织细胞原位杂交及图像分析技术 ,检测cNOS(eNOS和nNOS)及iNOSmRNA在缺血再灌注肾组织中的表达 ,并测定肾组织NOS总活性及血肌酐 (Cr)。 结果 :① 3种NOS在正常肾组织中均有表达 ,其中eNOS表达最丰富 ,cNOS/iNOS比值为 2 2 9。②缺血时 ,肾组织NOS总活性显著下降 ,3种NOSmRNA在皮质、髓质及小球中的表达均下调 ,以eNOS最显著 ,cNOS/iNOS比值呈下降(2 0 1)趋势。③再灌注后 ,3种NOSmRNA的表达明显上调 ,以iNOSmRNA最明显 ,cNOS/iNOS比值降至 1 77。④肾缺血注射丹参后再灌注 ,iNOSmRNA表达明显下调 ,而nNOSmRNA则显著上调 ,cNOS/iNOS比值处于正常范围 (2 14) ,Cr含量下降至正常水平。 结论 :①皮质肾小管上皮中iNOS活性升高与再灌注后肾功能进一步受损密切相关。②缺血再灌注肾损伤中 ,丹参抑制iNOSmRNA和促进cNOSmRNA的表达是其介导肾保护效应的重要分子机制。③cNOS/iNOS比值的恒定对肾血流量和肾小球滤过率 (GFR)的调节可能具有重要的意义
Objective: To explore the molecular mechanism of protective effect of salvia miltiorrhiza on renal ischemia reperfusion injury. METHODS: Using ischemic-reperfused renal injury model in rats, the expression of cNOS (eNOS and nNOS) and iNOS mRNA in renal tissue of ischemia-reperfusion injury were detected by in situ hybridization and image analysis. Total activity and serum creatinine (Cr). RESULTS: All three NOS were expressed in normal renal tissues. Among them, the eNOS expression was the most abundant, and the cNOS/iNOS ratio was 229. 2In ischemia, the total activity of NOS in renal tissue was significantly decreased, and the expression of 3 NOS mRNA was down-regulated in the cortex, medulla, and glomerulus, with eNOS being the most significant, and the cNOS/iNOS ratio decreasing (201). 3 After reperfusion, the expression of three kinds of NOS mRNA was significantly up-regulated, iNOS mRNA was the most obvious, and the cNOS/iNOS ratio was decreased to 177. 4 After renal ischemic injection of Salvia miltiorrhiza, iNOS mRNA expression was significantly down-regulated, while nNOS mRNA was significantly up-regulated. The cNOS/iNOS ratio was in the normal range (2 14). Cr content decreased to normal levels. Conclusion :1 The increase of iNOS activity in cortical tubular epithelium is closely related to the further impairment of renal function after reperfusion. 2 In ischemic-reperfused renal injury, salvia miltiorrhiza inhibits iNOS mRNA and promotes the expression of cNOS mRNA is an important molecular mechanism that mediates renal protective effects. 3 The constant cNOS/iNOS ratio may have important implications for renal blood flow and glomerular filtration rate (GFR) regulation