丹参对大鼠缺血再灌注肾组织一氧化氮合成酶mRNA表达的影响

目的：探讨丹参对肾缺血再灌注损作保护效应的分子机制。方法：以大鼠缺血再灌汪肾损伤为模型，采用组织细胞原位杂交有图像分析技术技术，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总活性有血肌酐（Cr）。结果：①3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2．29。②缺血时，肾组织NOS总活性显著下降，3种NOSmRNA在皮质、髓质有小球中的表达均下调，以eNOS最显著，cNOS／iNOS比值呈下降（2．01）趋势。③再灌注后，3种NOSmRNA的表达明显上调，以iNOSmRNA最明显，cNOS／iNOS的比值降至1．77。④肾缺血注射丹参后再灌注，iNOSmRAN表达明显下调，而nNOSmRAN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活性升同与再灌汪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。

Influence of Salvia Miltiorrhiza(SM)on the Expression of Nitric Oxide Synthase(NOS)mRNA of Rat Kidney Exposed to Ischemia Reperfusion (I/R) Injury

Objective:To investigate the molecular mechanism of the protective effect to SM on renal I/R injury Methods:A model of Wistar rat renal I/R was established.Then,the expression and content of three kinds of NOS mRNAs of kodney were detected by in situ hybridization and graphic analysis technique.NOS activity of renal tissues and serum creatinine(Cr)were also detected.Results:(1)3 NOSs were expressed in normal kidney tissues,eNOS was the richest;cNOS/iNOS was 229;(2)when renal ischemia occurred,NOS activity of renal tissues was decreased signifcantly and accompanied by downregulation of the three NOS mRNAs,especially eNOS mRNA,cNOS/iNOS(2.01)tended to decrease;(3)After renal reperfusion,all the three NOS mRNAs were up-regulated signifcantly,especially iNOS mRNA,cNOS/iNOS was obviously decreased(1.77);(4)After SM was used,iNOS mRNA was down-regulated significantly,and Cr went down to the normal level,but nNOS mRNA was up-regulated significantly.cNOS/iNOS went to the normal level(2.14).Conclusion:(1)After renal ischemia reperfusion,the increase of iNOS activity in tubules is closely related to the obvious damage of renal function;(2)Both inhibition of iNOS and improving of cNOS might be an important molecular mechanism for which SM modulates this protective effect on renal I/R injury;(3)Keeping cNOS/iNOS constant may be important for modulation of renal blood flow and glomerular filtration rate(GFR).