一氧化氮对脑缺血及血管性痴呆形成机制的实验研究

Role of nitric oxide in pathogenesis of acute cerebral ischemia and ensuing vascular dementia

为探讨一氧化氮（ＮＯ）参与血管性痴呆（ＶＤ）的形成及其作用机制，采用改良的Ｐｕｌｓｉｎｅｌｉ４－血管阻断（４－ＶＯ）方法建立ＳＤ大鼠急性全脑缺血和ＶＤ模型，同时采用ＮＯ－２／ＮＯ－３法（硝酸还原酶法）测定脑缺血早期和痴呆形成过程中以及分别经一氧化氮合酶（ＮＯＳ）抑制剂Ｌ－ＮＮＡ和底物Ｌ－Ａｒｇ干预后海马区ＮＯ水平及其动态变化，并对照各组迷宫试验的行为学定量和动态观察。结果：脑缺血早期海马区ＮＯ的变化对ＶＤ形成有重要的影响。说明ＮＯ途径参与了急性脑缺血及其ＶＤ形成的全过程，但在不同阶段可能发挥不同作用；一旦ＶＤ形成，则不论早期脑部ＮＯ水平如何。

In this study, a modified Pulsinelli′s 4-vessel occlusion method was used to establish the models of acute cerebral ischemia and vascular dementia (VD) in Sprague-Dawley (SD) rats. NO - 2/NO - 3 method was carried out to observe the NO level changes in hippocampus in the acute stage and during the process of VD development and after administration of NOS inhibitor L-NNA and NOS substrate L-Arg respectively as compared with the behavior changes. Results In the 4-VO group, the hippocampus NO level increased markedly 30 min after operation. About 2 weeks after operation, VD was found in 4-VO group. The hippocampus NO level decreased markedly in L-NNA-treated group while increased significantly in L-Arg-treated group. VD development was shown about 1 week after operation in the fromer while about 3 weeks after operation in the latter. NO determination showed that NO reached its highest peak 3 hours after occlusion and gradually decreased 3 days later. At the time of VD development, it rose again to a much higher level. Conclusions: The modified Pusinelli′s 4-Vessel occlusion method is fruitful and reliable for the establishment of VD in animals. NO pathway is involved in the whole process from acute ischemia to VD development but it plays a different role in different stages. Whenever VD occurs, VD will become irreversible no matter what is the level of NO in the early stage.