一氧化氮在肝硬化大鼠睾丸功能障碍发生中的作用

目的探讨一氧化氮(NO)在肝硬化睾丸功能障碍发生中的作用. 方法采用胆管结扎(BDL)复制肝硬化模型,应用硝酸酶还原法测定大鼠血清和睾丸组织匀浆的NO浓度,应用放射免疫分析法测定血清睾酮浓度,同时检测大鼠附睾精子密度和精子活率. 结果肝硬化(HC)组大鼠血清和睾丸组织匀浆NO水平分别为(4.165±1.162)μmol/L和(1.305±0.087)μmol/g,假手术(SO)组大鼠血清和睾丸组织匀浆NO水平分别为(0.535±0.237)μmol/L和(0.720±0.063)μmol/g,HC组显著高于SO组.HC组血清睾酮水平[(0.049±0.020)μg/L]、附睾精子活率(16.46%±4.84%)及精子密度[(86.89±33.17)×106个/ml]均显著低于SO组[分别为(2.680±0.403)μg/L、62.45%±9.21%和(299.43±53.85)×106个/ml],而持续给予小剂量NOS抑制剂L-NAME(HC-NAME组)(0.5mg@kg-1@d-1)达一周,HC-NAME组大鼠血清及睾丸组织NO水平分别为(1.975±0.406)μmol/L和(0.950±0.057)μmol/g,较HC组显著降低.同时HC-NAME组血清睾酮水平、附睾精子活率和精子密度较HC组均显著增高,分别为(0.993±0.179)μg/L、33.85%±4.93%和(188.94±38.34)×106个/ml. 结论 NO在肝硬化大鼠睾丸功能障碍发生中起重要作用,小剂量应用NOS抑制剂L-NAME,肝硬化大鼠NOS持续抑制引起的睾丸功能障碍得到不同程度改善,表明在治疗肝硬化睾丸功能障碍患者时体内给予NOS抑制剂的可能性.

Action of nitric oxide on testicular dysfunction in cirrhotic rats

OBJECTIVE: To investigate the action of nitric oxide (NO) on testicular dysfunction in cirrhotic rats. METHODS: Cirrhotic rats were induced by bile duct ligation (BDL). Concentration of NO in the serum and homogenates of the testicular tissue in biliary cirrhotic rats, L-NAME rats, and sham operated rats were measured by assay of nitrate reductase. Concentrations of testosterone in the serum of 3 groups were measured by radioimmunoassay. Sperm density and percent of motive sperm in the epididymis of the rats were determined. RESULTS: Concentrations of NO in the serum and homogenates of the testicular tissue of cirrhotic rats were significantly greater than those of sham operated rats (4.165 micromol/L 1.162 micromol/L, and 1.305 micromol/g 0.087 micromol/g vs 0.535 micromol/L 0.237 micromol/L and 0.720 micromol/g 0.063 micromol/g). Concentrations of testosterone in the serum, the sperm density and percent of motive sperm in the epididymis were significantly lower in cirrhotic rats than sham operated rats (0.049mug/L 0.020 microgram/L, 16.46% 4.84%, and 86.89 10(6)/ml 33.17 10(6)/ml vs 2.680 microgram/L 0.403 microgram/L, 62.45% 9.21%, and 299.43 10(6)/ml 53.85 10(6)/ml). By contrast, the administration of a low dose of L-NAME (0.5 mg/kg per day) for one week to cirrhotic rats was associated with a significant reduction in concentration of NO (1.975 micromol/L 0.406 micromol/L and 0.950 micromol/g 0.057 micromol/g) and a significant increase in concentration of testosterone in the serum, the sperm density and percent of motive sperm in the epididymis (0.993 microgram/L 0.179 microgram/L, 33.85% 4.93%, and 188.94 10(6)/ml 38.34 10(6)/ml). CONCLUSIONS: NO is associated with testicular dysfunction in cirrhosis. The testicular dysfunction induced by cirrhosis can obtain improvement by using low dose of L-NAME.