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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CRF血液透析贫血患者15例及对照组15例,CRF贫血动物模型,以及透析过程中出现低血压的34例患者,应用分光光度法及放免法观察用药或透析前后血浆一氧化氮(NO)代谢产物(NO2/NO3)及内皮素-1(ET-1)的变化。结果: ①CRF贫血患者及贫血鼠用r-HuEPO治疗16周后,红细胞压积(Hct)升高,血压升高,ET-1升高(P<0.01),血浆NO2/NO3下降(P<0.01),而对照组用药前后无明显变化(P>0.05)。②在用药16周后,RT- PCR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)。③透析低血压患者透析后NO2/NO3含量增高,ET-1含量减少(P<0.05)。结论:研究表明r-HuEPO导致高血压与iNOSmRNA减少、合成NO减少和ET-1增加有重要的关系。
Objective: To investigate the mechanism of r-HuEPO in the treatment of hypertension induced by chronic renal failure (CRF) and its prevention and treatment. Methods: 15 cases of hypertensive CRF hemodialysis anemia and 15 cases of control group, CRF anemia animal model and 34 cases of hypotension during dialysis were treated with r-HuEPO. The patients were treated with spectrophotometry and radioimmunoassay (NO2 / NO3) and endothelin-1 (ET-1) before and after dialysis. Results: ① After 16 weeks treatment with r-HuEPO in CRF anemia and anemia rats, hematocrit (Hct) increased, blood pressure increased, ET-1 increased (P <0.01), plasma NO2 / <0.01), while there was no significant difference in the control group before and after treatment (P> 0.05). ② After 16 weeks of treatment, iNOS mRNA in renal cortex and medulla decreased significantly (P <0.05) in experimental group compared with control group by RT-PCR. ③ The level of NO2 / NO3 increased and the content of ET-1 decreased after dialysis in patients with dialysis hypotension (P <0.05). CONCLUSIONS: Studies have shown that r-HuEPO leads to hypertension and has a significant relationship with reduced iNOS mRNA, reduced synthesis of NO and increased ET-1.