5/6肾切除对尿毒症心衰大鼠主动脉NO病理生理机制的影响研究

Impact study of aortic NO pathologic physiology mechanism of 5/6 nephrectomy to rats with uremia heart failure

目的探讨5/6肾切除对尿毒症心衰大鼠一氧化氮(NO)病理生理机制的影响。方法将50只雄性SD大鼠随机分为肾切除(NX)组30只和假手术(Sham)组20只。2组常规检测血清尿素氮(BUN)、肌酐(Scr)及24h尿蛋白定量,采用Griess法测定NO含量和一氧化氮合酶(NOS)活性,实时定量聚合酶链式反应(RT-PCR)检测内皮型NOS(eNOS)和诱导型NOS(iNOS)的基因表达。结果 NX组术后第6、8周血清BUN、肌酐Scr及24h尿蛋白定量均高于Sham组;eNOS活性低于Sham组;eNOSmRNA的表达水平低于Sham组,iNOSmRNA的表达水平高于Sham组,差异均有统计学意义(P<0.05和P<0.01)。结论主动脉(包括血管内皮细胞)被损伤后,iNOS增加,而eNOS减少,从而使主动脉的舒张度降低而最终导致心衰。对于5/6肾切除大鼠,受损的主动脉NO途径可能是尿毒症诱发心衰的机制之一。

Objective To investigate the pathophysiological mechanisms of NO system of 5/6 nephrectomy to rats with uremia heart failure.Methods 50 male SD rats were randomly divided into NX group（30 cases） and Sham group（20 cases）.The BUN,Scr and 24h proteinuria excretion of 2 groups were tested routinely.The NO contents and NOS activity were assayed by Griess method,and the iNOS and eNOS expression were assayed by RT-PCR.Results The BUN,Scr and 24h proteinuria excretion at postoperative 6,8 weeks of the NX group were higher than that of the Sham group;the eNOS activity of the NX group was lower than that of the Sham group;the mRNA expression level of eNOS of the NX group was lower than that of the Sham group;the mRNA expression level of iNOS of the NX group was higher than that of the Sham group,the differences were statistically significant（P〈0.05 and P〈0.01）.Conclusion After aorta（including endothelium） was injured,iNOS derived NO increasing and meanwhile eNOS derived NO decreasing,so that,aortic relaxing tension was declined,which may finally cause heart failure.Injured aortic NO pathway in 5/6 nephrectomized rats may be one of the mechanism of uremia-induced heart failure.