妥泰对沙土鼠脑缺血再灌注损伤保护作用的实验研究

目的 研究妥泰对沙土鼠脑缺血再灌注损伤的保护作用及作用机制。方法 采用沙土鼠双侧颈总动脉结扎制成的全脑缺血模型。56只沙土鼠随机分为假手术组、缺血组、治疗组和预防组。预防组的动物分别给予大、小剂量的妥泰(100 mg/kg、50mg/kg)灌胃观察3天而行手术,术后24小时处死动物;治疗组的动物术后立即分别给于大、小剂量的妥泰(100 mg/kg、50mg/kg)灌胃观察7天处死动物。测定各组沙土鼠血、脑组织中的MDA、SOD的含量。光镜和电镜下观察脑组织CA_1区的病理及超微结构改变。结果 与缺血组相比,妥泰治疗组和妥泰预防组脑组织中的MDA含量明显降低(P<0.01),而SOD含量明显增高(P<0.01)。光镜和电镜下观察发现,妥泰治疗组和妥泰预防组的脑CA_1区缺血改变较缺血组减轻,且大剂量组缺血改变明显减轻。结论 妥泰对沙土鼠脑缺血再灌注损伤具有良好的保护作用,且保护作用与妥泰的剂量大小有关。其脑保护作用机制之一为妥泰能有效抑制氧自由基的产生及毒性。

The topamax protective effect on cerebral ischemic reperfusion damage in gerbils

Objective To study the protective effect and mechanism of Topamax on cerebral ischemic reperfusion damage in gerbils. Methods Global cerebral ischemic model was made by occlusion of bilateral arteries in gerbils. 56 gerbils were randomly assigned into 8 groups, including sham-operation group, ischemia group, preventative group and treatable group. In the preventative group, the higher and lower dose of topamax (100mg/kg 50mg/kg) were given respectively for 3 days before operation and the animals were killed at 24 hours after the operation; In the treatable group, the higher and lower dose of topamax (100mg/kg 50mg/kg) were given respectively for 7 days after operation, then the animals were killed. The MDA, SOD concentrations of blood plasma and brain tissue in every group were measured; The histological examinations of CA_1 area in their brain were carried out under the light and dectron microscope. Results The MDA concentrations of blood plasma and brain tissue in TPM preventative group and treatable group were obviously lower than that in ischemic group (P<0.01), The SOD concentrations were significantly higher than that in ischemic group (P<0.01). The ischemic reperfusion group showed obvious ischemic changes of the cells in CA_1. Compared with ischemic group, The CA_1 ischemic changes were moderated in the low dose of topiramate administration group and significantly reduced in the high dose of topiramate administration group. Conclusions Topamax has a neuroprotective effect on cerebral ischemic reperfusion damage in gerbils and reduced neuronal damage in a dose-dependent manner. The administration of high dose of topamax could significantly suppressed neuronal cell ischemic damages. It suggests that TPM could inhibit the cytotoxic effect of oxygen free radicals on cerebral neurons in gerbils.