arcaine对大鼠局灶性脑缺血损伤的神经保护作用

Neuroprotective effects of arcaine on focal cerebral ischemia in rats

目的观察N-甲基-D-天冬氨酸(NMDA)受体/通道复合物多胺位点拮抗剂arcaine对脑缺血损伤的神经保护作用。方法将45只Wistar大鼠随机分为对照组、缺血模型组、术前24h组、术前1h组及术后1h组。后4组大鼠均采用线栓法阻断大脑中动脉制作急性脑梗死模型。缺血模型组在造模成功后1h给予生理盐水(0.4ml/kg),术前24h组、术前1h组和术后1h组分别在术前24、1h和术后1h给予3mg/kg arcaine。检测大鼠神经功能行为、脑梗死体积,并观察光镜及电镜下脑组织损伤情况。结果神经功能评分显示,术前24h组、术前1h组和术后1h组大鼠神经功能行为评分(1.25±0.46、1.33±0.50、1.40±0.58分)与缺血模型组(2.63±0.52分)相比有显著差异(P<0.05),且术后给药对神经运动功能障碍的改善效果较术前给药效果差(P<0.05)。术前24h、术前1h组和术后1h组大鼠脑梗死体积百分比(分别为5.72%±2.91%、26.36%±5.30%、36.35%±6.66%)较缺血模型组(51.10%±3.86%)明显减少(P<0.05);术后1h组大鼠脑梗死体积百分比较术前24、1h组增加(P<0.05)。除对照组外,各组光镜下病理分级结果差异无统计学意义。电镜下观察各组大鼠皮层及海马神经元均有不同程度的变性坏死,其中缺血模型组病理损害最为严重。结论arcaine能够显著减少脑梗死的体积、减轻梗死所致的神经功能损伤,且预防给药效果更佳,但是arcaine对缺血所致神经元超微结构的损伤无明显逆转作用。

Objective To observe the neuroprotective effect of arcaine, an antagonist of receptor of N-methyl-D-aspartate （NMDA） and （or） channel complex polyamines site, on cerebral isehemia. Methods Forty-five Wistar rats were randomly divided into 5 groups： control group, ischemia model group, 24h preoperative group, lh preoperative group and lh postoperative group. Acute cerebral infarction model was reproduced in rats of the latter four groups with middle cerebral artery occlusion （MCAO） using ligature method. Once the ischemia model was successfully established, rats in the latter three ischemia model groups were given arcaine （3mg/kg） at 24h and lh before operation and lh after operation, respectively, while normal saline （0. 4ml/kg） was injected to the rats in the control group. Neurological function behavior and cerebral infarct volume were assessed, and pathological features of brain tissue were observed under light- and electron microscope. Results Neural function scores of the rats in 24h preoperative group, 1h preoperative group and 1h postoperative group were 1.25±0. 46, 1. 33±0. 50 and 1.40±0. 58, respectively, which were significantly different from that in ischemia model group （2. 63±0. 52, P〈0. 05）. Results also indicated that preoperative administration of areaine had a better therapeutic effects than that of postoperative administration （P〈0. 05）. The percentage of cerebral infarct volume of the rats in 24h preoperative group, 1h preoperative group and lh postoperative group were 5. 72%±2. 91%, 26. 36%±5.30% and 36. 35%±6. 66%, respectively, and they were significantly smaller than that in ischemia model group （51.10%±3. 86%, P〈0. 05）, while that in the lh postoperative group was significantly larger than that in 24h and lh preoperative groups （P〈0. 05）. No significant difference was found in pathological grading among the groups with the exception of control group. It was shown by electron microscopy that different degrees of degeneration and necrosis occurred in the cerebral cortex and hippocampal neurons of the rats in all the groups, especially the isehemia model group. Conclusion Administration, especially preemptive administration of arciane may significantly decrease the cerebral infarct volume and abate neuroftmctional lesions induced by ischemia, but it has no restorative effects on the injured ultrastructure of neurons.