NOS抑制剂对缺血再灌注脑组织rCBF及白细胞浸润的影响研究

Investigation of Effects of NOS Inhibitors on the Regional Cerebral Blood Flow and Leukocytes Infiltration during the Cerebral Ischemia and Reperfusion in Rats

目的应用非选择性NOS抑制剂L－NAME和选择性iNOS抑制剂AG治疗鼠大脑中动脉缺血再灌注损伤。通过对脑梗死体积、rCBF和白细胞浸润程度的观察，研究探讨不同类型NOS抑制剂治疗脑梗死的机制。方法采用线检法制作鼠大脑中动脉缺血再灌注模型，不同缺血及再灌注时间测定脑梗死体积、rCBF、缺血脑组织MPO酶活性。结果应用L－NAME（15mg／kg，ip）不但阻碍再灌注后rCBF的恢复，也增加缺血脑组织MPO酶活性（中性白细胞浸润增加），致脑梗死体积增加，脑损害加重；而AG（150mg／kg，ip）可有效降低脑梗死体积，且不影响rCBF的恢复和中性白细胞浸润。结论早期过度抑制神经元和内皮细胞NO对血流量的调节和抗白细胞粘附浸润作用可能是L-NAME加重缺血再灌注脑损害的重要原因之一，而选择性iNOS抑制剂有确切的脑保护作用。

The purpose of study was to investigate the machanism of drug therepy for ischemic/reperfusional brain damage by the administration of nonselective NOS inhibitor and selective iNOS inhibitor, with the measurement of the brain infarction volume (IV% ), rCBF and leukocytes infiltration. Methods Rat models of cerebral middle artery ischemic and reperfusion were established by suture method. The IV%, rCBF and MPO were measured at different time points. Results The results showed that administration of L-NAME increased MPO activity of the ischemic brain tissues and decreased rCBF during the reperfusional period. The aminoguanidine had an effect to decrease IV% and no effect on rCBF and MPO activity of the ischemic brain tissues. Conclusion Early inhibiting NOS of neurons and endothelia which could produce the NO for the regulation of the rCBF and antiadhesion may be an important reason for L-NAME aggravating the ischemic and reperfusional brain damage. Selective iNOS inhibitor aminoguanidine is convinced to have an exact protective effect on ischemic and reperfusional brain tissues with its effect of antineurotoxin on NO.