醒脑静固体制剂对缺血性脑损伤大鼠恢复早期的保护作用

目的:初步研究醒脑静固体制剂对缺血性脑损伤大鼠恢复早期的保护作用及其作用机制.方法:线拴法制备永久性局灶性中动脉阻断脑缺血(pMCAO)大鼠模型,分为模型组、醒脑静12,25,50 mg· kg-1剂量组,丁苯酞(NBP) 70 mg·kg-1组,ig给药12 d并设假手术组.在术后3,6,9,12,14 d,检测动物平衡能力、缺血前肢触觉、前肢肌肉张力等指标的改善状况,取材并测定动物缺血侧脑组织超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量.结果:与假手术组相比,pMCAO模型动物表现出神经功能缺损症状,在缺血后3d横木行走评分降低65％,撕除胶布潜伏期增加13.9倍,前肢拉力减小39.7％(P＜0.01).其中,醒脑静12,25,50 mg· kg-1在缺血后6～14 d分别降低神经功能缺损评分(P＜0.05或P＜0.01),提高横木行走能力评分(P ＜0.05或P＜0.01),缩短撕除潜伏期(P＜0.05或P＜0.01),提高前肢抓握力(P＜0.05或P＜0.01).同时醒脑静可显著降低缺血侧脑组织中MDA含量(P＜0.01).结论:醒脑静固体制剂对缺血性脑损伤恢复早期大鼠模型具有一定保护作用,其作用机制可能与抑制脂质过氧化反应产物MDA含量,从而减轻氧化损伤有关.

Protective Effect of Solid Preparation of Xingnaojing from Neurological Defect and Oxidative Damage in pMCAO Model Rats in Early Convalescence

Objective: To investigate protective effect of solid preparation of Xingnaojing (XNJ) in middle cerebral artery occlusion (MCAO) model in rats, and explore related mechanism. Method: Cerebral middle artery was occluded with nylon suture to establish permanent middle cerebral artery occlusion (pMCAO) model. Rats with occlusion were randomly divided into model group, XNJ 12, 25, 50 mg·kg^-1 groups, and Butylphthalide (NBP) 70 mg·kg^-1 group, which were ig administered for 12 days, taking rats underwent same procedure except artery occlusion as the sham group. At day of 3, 6, 9, 12, 14 from the occlusion, four different neurological tests were applied to all animals: neurological defects score, beam-walking test, tape-removal test, and pulling-force test, with regard to detection of sensorimotor defects, motor coordination defects, and strength of forelimbs. At the 14^th day, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in ischemic cerebral tissues were measured after neurological tests. Result: Compared with the sham group, there were obvious neurological defects in pMCAO model rats. At the 3^rd day after occlusion, score of beam-walking test in the model group reduced by 65% (P<0.01), time for tape-removing increased 13.9 times (P<0.01), as well as strength of forelimbs reduced to 39.7% (P<0.01). From 6^th day to 14^th day after occlusion, compared with the model group, in the 12, 25, 50 mg·kg^-1 dose-groups of XNJ, neurological defects scores reduced (P<0.05, P<0.01), scores for beam-walking test improved (P<0.05, P<0.01), time for tape-removing shortened (P<0.05, P<0.01), strength of forelimbs increased (P<0.05, P<0.01). In addition, content of MDA in the ischemic brain tissue of all dose-groups of XNJ significantly reduced (P<0.01). Conclusion: Solid preparation of XNJ has protective effect on permanent cerebral ischemia model in rats. In early convalescence after pMCAO, it is able to improve recovery of neurological defects in rat, which might relate to its inhibition on generation of MDA to alleviate oxidative stress.