L-NAME对新生鼠缺氧性脑损伤内源性NO和ET的影响

Effect of L-NAME on NO and ET in newborn rats with hypoxic brain injuries

目的 用新生大鼠急性缺氧模型 ,探讨 NO合成酶抑制剂 L-硝基 -精氨酸甲酯 (L- NAME)在缺氧后脑损伤中的作用 ,进而探讨一氧化氮 (NO)和内皮素 (ET)在早期缺氧性脑损伤中的作用地位 .方法 检测正常对照组、缺氧组和缺氧前应用 L- NAME预处理的新生大鼠血浆 ET及脑组织匀浆 NO含量及 NOS的活性 ,并观察各组大鼠脑组织病理改变及毛细血管充盈不良程度 .结果 缺氧组血浆 ET水平较正常对照组显著升高 (P<0 .0 1) ,而脑 NO水平及 NOS活性无显著变化 (P>0 .0 5 ) ,脑毛细血管充盈不良程度与正常对照组相比明显加重 (P<0 .0 5 ) ;L- NAME组血浆 ET水平较缺氧组显著升高 (P<0 .0 5 ) ,脑 NO含量及 NOS活性较缺氧组显著下降 (P<0 .0 1) ,脑毛细血管充盈不良程度与缺氧组相比明显加重 (P<0 .0 5 ) .结论 急性缺氧早期 ,ET异常增高是脑损伤的主要因素 ;此时抑制内源性 NO的合成 。

AIM To explore the role of nitric oxide (NO) and endothelin (ET) in the early phase of hypoxic brain injuries by examing the effect of N ω nitro L arginine methyl ester (L NAME), an inhibitor of nitric oxide synthase (NOS), on brain NO production and serum ET level in newborn rats with hypoxic brain injuries. METHODS The rats were divided into normal control group, hypoxia group and L NAME+ hypoxia group. The ET level in serum, NO production, NOS activity, pathology and capillary perfusion in brain were investigated in 3 groups. RESULTS The serum ET level of hypoxia group was significantly higher than that of controls ( P <0.01), but NO production and NOS activity were not significantly different between 2 groups ( P >0.05), and the brain capillary perfusion was more serious in hypoxia group that that in controls. Compared with the hypoxia group, the serum ET level of L NAME+ hypoxia group was increased significantly ( P <0.05), NO production and NOS activity in brain was decreased significantly ( P <0.01), and brain capillary perfusion was serious significantly ( P < 0.05 ). CONCLUSION Abnormal increase of serum ET in early phase of acute hypoxia is the main factor of brain injury; NOS inhibitor L NAME may make microcirculation dysfunction worse and lead to a further hypoxic ischemic brain injury.