基因重组促红细胞生成素导致高血压的机制研究

Study on mechanism of hypertension related to r HuEPO

目的：探讨基因重组促红细胞生成素（ｒ－ＨｕＥＰＯ）在治疗慢性肾衰（ＣＲＦ）贫血中导致高血压的机制及防治对策。方法：对ｒ－ＨｕＥＰＯ治疗中出现高血压的ＣＲＦ血液透析贫血患者１５例及对照组１５例，应用分光光度法及放免法观察治疗前后血浆一氧化氮代谢产物（ＮＯ２－／ＮＯ３－）及内皮素－１（ＥＴ－１）的变化。同时用大鼠进行对照试验。结果：１．ＣＲＦ贫血患者及贫血鼠用ｒ－ＨｕＥＰＯ１６周后，红细胞压积（Ｈｃｔ）升高、血压升高，ＥＴ－１增加（Ｐ＜０．０１），血浆ＮＯ２－／ＮＯ３－下降（Ｐ＜０．０５），而对照组用药前后无明显变化（Ｐ＞０．０５）。２．在用药１６周后，ＲＴＰＣＲ测得实验组大鼠肾皮质及髓质ｉＮＯＳｍＲＮＡ比对照组明显减少（Ｐ＜０．０５）。结论：研究表明ｒ－ＨｕＥＰＯ导致高血压与ｉＮＯＳｍＲＮＡ减少。

Objective:To investigate the pathogenesis of r HuEPO related hypertension.Methods:Change of nitrous oxide(NO) production and endothelin 1(ET 1) was observed in anemi patients with chronic renal failure(CRF) during hemodialysis(HD) and anemic rats with CRF after 16 weeks of receiving r HuEPO treatment resulting in hypertension and control groups.The level of plasma NO metabolites (NO - 2/NO - 3) and ET 1 was determined .Then inducible NO syunthase mRNA (iNOSmRNA) was detected by RT PCR in rats renal cortical and medullary.Results:Hct、BP and the levels of plasma ET 1 were significantly higher ( P <0.01) ,but the levels of plasma NO were markedly lower ( P <0.05).There was no change of those in control groups ( P > 0.05 ).iNOSmRNA level was obviously lower in CRF rats than that of control rats. Conclusion:The decreases of iNOSmRNA and NO,and increase of ET 1 might play an important role in the development of hypertension related r HuEPO.