促红细胞生成素与一氧化氮合酶抑制剂对肝硬化大鼠高动力循环状态的影响

Effects of erythropoietin or nitric oxide synthesis inhibitor on hyperdynamic circulatory state in cirrhotic rats.

目的观察促红细胞生成素（简称促红素）或一氧化氮合酶（ＮＯＳ）抑制剂Ｎ－硝基－Ｌ－精氨酸甲酯（Ｌ－ＮＡＭＥ）对肝硬化大鼠高动力循环状态的影响。方法制造肝硬化大鼠模型，用Ｌ－ＮＡＭＥ（０．５ｍｇｋｇ－１ｄ－１）胃管内注入或促红素（１００Ｕ／ｋｇ）皮下注射治疗２周；用５７Ｃｏ标记微球技术，观察大鼠血流动力学指标；用荧光比色法测血清一氧化氮（ＮＯ）含量。结果肝硬化大鼠全部出现高动力循环状态，血清ＮＯ含量显著高于正常对照组。促红素和Ｌ－ＮＡＭＥ治疗组高动力循环状态明显改善，血清ＮＯ含量均显著低于肝硬化未治疗组。结论小剂量Ｌ－ＮＡＭＥ可逆转肝硬化大鼠的高动力循环状态；促红素致Ｈｂ增高，进而加速ＮＯ灭活，对肝硬化高动力循环可能具有潜在治疗作用。

Objective To observe the effects of erythropoietin or nitric oxide synthesis (NOS) inhibitor N G nitro L arginine methyl ester (L NAME) on hyperdynamic circulatory state in rats with cirrhosis.Methods Cirrhotic rat model was made. Cirrhotic rats were treated with NOS inhibitor L NAME (0.5 mg·kg -1 ·d -1 ) by gavage or with erythropoietin (100U/kg) injected subcutaneously for two weeks. The hemodynamic parameters in cirrhotic rats treated with L NAME or with erythropoietin were determined by using 57 Co labled microsphere technique. Serum nitric oxide (NO) levels were also measured by using a fluorometric assay.Results Hyperdynamic circulatory state was observed in all rats with cirrhosis. Serum NO levels in cirrhotic rats were significantly higher than that in normal controls. Hyperdynamic circulation status in cirrhotic rats treated with erythropoietin or with L NAME was markedly attenuated. As compared with untreated cirrhotic rats, serum NO concentration in erythropoietin treated and L NAME treated cirrhotic rats were significantly lower. Conclusion L NAME treatment could reverse the hyperdynamic circulatory state in cirrhotic rats which might be ameliorated by inactivation of overproduced NO by increasing hemoglobin with erythropoietin.