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目的 测定自发性高血压大鼠 (SHR)与WKY大鼠组织肾上腺髓质素 (ADM )含量和中性内肽酶 (NEP)活性及其表达水平 ,以探讨NEP的变化在高血压时组织ADM水平升高中的意义。方法 采用放射免疫分析方法和荧光分光光度法分别检测血浆和组织的ADM含量和NEP的活性 ,同时用半定量RT PCR和免疫组织化学染色法分别检测组织NEPmRNA和NEP蛋白的表达和分布。结果 ADM和NEP广泛分布于大鼠的血浆和组织 ,SHR的ADM含量在各组织普遍高于WKY大鼠。SHR心脏和小肠NEP的活性和mRNA表达均显著低于WKY大鼠 ,ADM含量与NEP活性呈负相关。反之 ,SHR血浆和肾脏NEP活性、肾脏NEPmRNA水平与蛋白量均高于WKY大鼠 ,ADM含量与NEP活性呈正相关。在肺脏和主动脉 ,NEP的活性无明显变化。结论 NEP在自发性高血压大鼠各组织器官中的变化与ADM含量的变化不一致 ,提示高血压时组织局部的NEP对ADM含量的影响不同。
Objective To determine the content of adrenomedullin (ADM) and the activity of neutral endopeptidase (NEP) in spontaneously hypertensive rats (SHR) and WKY rats and the expression of NEP in order to investigate the changes of NEP in hypertensive rats The significance of the level rise. Methods Radioimmunoassay and fluorescence spectrophotometry were used to detect the content of ADM and the activity of NEP in plasma and tissue respectively. Meanwhile, the expression and distribution of NEP mRNA and protein were detected by semi-quantitative RT-PCR and immunohistochemical staining. Results ADM and NEP were widely distributed in plasma and tissues of rats. The content of ADM in SHR was generally higher in all tissues than in WKY rats. The activities and mRNA expressions of NEP in the heart and small intestine of SHR were significantly lower than those in WKY rats. The content of ADM was negatively correlated with the activity of NEP. In contrast, NEP activity and renal NEP mRNA levels and protein levels in SHR plasma and kidney were higher than those in WKY rats, and ADM content and NEP activity were positively correlated. In the lungs and aorta, NEP activity did not change significantly. Conclusion The changes of NEP in tissues and organs of spontaneously hypertensive rats are not consistent with the change of ADM contents, suggesting that the influence of local NEP on ADM content in hypertensive rats is different.