缺血再灌流肾组织内皮素-1及其受体基因表达的实验研究

Expression of endothelin 1 mRNA and its receptors in rat kidney following renal ischemia reperfusion

为了探究内皮素１（ＥＴ１）对肾功能的影响和作用方式，采用斑点杂交和原位杂交方法对大鼠缺血６０分钟再灌注肾组织ＥＴ１及其受体亚型（ＥＴＡ、ＥＴＢ）的基因表达进行了研究。结果发现：再灌流１小时，ＥＴ１、ＥＴＡ、ＥＴＢｍＲＮＡ均明显升高；再灌流２４小时仍维持较高水平。ＥＴ１和ＥＴＡｍＲＮＡ杂交信号再灌流３小时达高峰。ＥＴ１ｍＲＮＡ主要分布肾皮质小血管内皮细胞、髓质肾小管和集合管，ＥＴＡ受体ｍＲＮＡ则分布于上述小血管的平滑肌细胞。ＥＴＢ受体ｍＲＮＡ于再灌流６小时达高峰，主要分布髓质肾小管、集合管。说明缺血再灌流肾内皮素受体亚型上调在皮质以ＥＴＡ为主，在髓质以ＥＴＢ为主，分别与增强表达的ＥＴ１结合导致肾皮质缺血和水钠代谢异常。

Expression of messenger endothelin 1 (ET 1) RNAs and its receptor subunits (ETA,ETB)were studied by northern blot hybridization in rat kidney following renal ischemia reperfusion.ET 1,ETA and ETB mRNA expressions were all evidently increased after 60 minutes of ischemia.ET 1 and ETA reached their maximal mRNA expression at 3 hours after ischemia.ET 1 mRNA distributed primarily on glomerular endothelial cells and tubular epithelial cells in cortex.ETA mRNA predominant presented on smooth muscle cells of renal cortex small arterioles.However,the peak time of ETB mRNA receptor was at 6 hour and mainly localized on renal medullary tubule epithelial and collecting duct cells.These findings suggested that ET 1 acts principally as a local paracrine/autocrine peptide.Renal ischemia during reflow might be resulted from increased ET 1 activating ETA receptors on vascular smooth muscle cells.ETB receptor accentuated expression on tubular epithelial cells binded in ET 1 or ET 3 might induce a renal natriuretic action and reduction of water excretion.