Study on the effects of neurotrophic factors on hypoxic-ischemic encephalopathy in fetal and newborn brain.

为探讨一氧化氮(NO)在体内微透析修复缺血性脑损伤中的作用。方法：7日龄SD大鼠用乌拉坦麻醉，纹状体内植入微透析探头(CMA11)，用林格氏液调节探头。实验分为3组：对照组、L精氨酸组(非合成药物)和N-硝基-L-精氨酸甲酯(L-NAME)(非合成酶抑制剂)组。在插入探头后，允许2-h时间稳定。暴露于8%O2中60分钟，然后用21%O2复氧。从缺氧前30min至实验结束，用探头向纹状体内注射L-精氨酸或L-NAME，剂量均为100ug/dl。细胞外多巴胺及其代谢产物二羟基苯乙酸(DOPAC)和高香草酸(HVA)的含量在缺氧60min时升高至缺氧前的2.4倍，复氧后恢复至基线水平。L-精氨酸组多巴胺浓度升高为基线的2.3倍，与对照组相当，而L-精氨酸组仅为基线的1.4倍。缺氧使细胞外多巴胺代谢产物DOPAC和HVA减少。提示抑制NO合成对预防缺氧性脑损伤有一定作用。

The present study was performed to investigate the role of nitric oxide (NO), one of the neurophic factors for the repair from the ischemic brain damage by the in vivo microdialysis technique.Method : 7-day-old Sprague-Dawley rats were anesthetized with urethane, and microdialysis probe (CMA11) was implanted into the striatum, and the probe was conditioned by the Ringer's solution. The animals were divided into three groups : Control group, L-arginine (NO synthetic drug) administered group, and N-nitro-L-arginine methyl ester (L-NAME) (NO synthase inhibitor) administered group. After insertion of probe, 2-h period was allowed for stabilization. They were exposed to 8% O2 for 60 minutes, and followed reoxygenation with 21% O2. Either L-arginine or L-Name at a dose of 100 ug/dl were injected to the striatum by a probe from 30 minutes before the onset of hypoxia to the end of experiment. Extracellular dopamine and the metabolites ; Dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined by the HPLC-electro-chemical technique.Results : The dopamine concentration in control group was increased to 2.4 times of the level before the hypoxia at the 60 minutes of hypoxia, and recovered to the baseline by the reoxugenation. The increment of the dopamine concentration in the L-arginine group was 2.3 times of the baseline, as highly as the controls, and that in the L-NAME group was as low as 1.4 times of the baseline. The extracellular dopamine metabolites, DOPAC and HVA,were decreased by the hypoxia. These results suggest that inhibition of NO systhesis plays a role for the prevention from the brain injury due to hypoxia.