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目的:观察不同剂量黄芩苷和栀子苷配伍(7:3)对SD大鼠脑缺血再灌注脑组织中CysLTs含量及神经元损伤,探讨其对脑缺血再灌注保护作用的剂量和时间窗。方法:将150只大鼠随机分为假手术组、模型组、尼莫地平治疗组、栀子苷和黄芩苷配伍治疗组。采用线栓法复制大鼠急性脑缺血再灌注损伤模型(MCAO),分别于缺血2h后再灌注3h,6h,24h,72h。采用尼氏体染色法观察神经元的病变及特点、酶联免疫吸附法检测脑组织中CysLTs含量。结果:根据动物行为学评分结果,黄芩苷和栀子苷配伍20mg/kg能改善大鼠脑缺血2h再灌注6h、24h时神经损伤引起的行为学异常;40mg/kg时能改善大鼠脑缺血2h再灌注3h、6h、24h时神经损伤引起的行为学异常;根据脑组织中CysLTs结果,最佳治疗时间窗和剂量分别为脑缺血2h再灌注24h,20 mg/kg;脑缺血2h再灌注72h,40 mg/kg;根据脑组织病理损伤观察结果,最佳治疗时间窗和剂量分别为脑缺血2h再灌注24h,20 mg/kg;脑缺血2h再灌注72h,40 mg/kg。结论:根据用药剂量最小化和治疗时间窗最大化的原则综合评价,根据动物行为学评分、脑组织中CysL Ts和病理观察结果,黄芩苷和栀子苷配伍治疗大鼠脑缺血再灌注损伤的最佳治疗时间窗和剂量为脑缺血2h再灌注24~72h,20~40mg/kg。
Objective: To observe the effects of different dosages of baicalin and geniposide (7: 3) on CysLTs content and neuronal damage in brain tissue of SD rats with cerebral ischemia and reperfusion, and to explore the dose and time of its protective effect on cerebral ischemia-reperfusion window. Methods: 150 rats were randomly divided into sham operation group, model group, nimodipine treatment group, geniposide and baicalin compatibility treatment group. The rat model of acute cerebral ischemia-reperfusion injury (MCAO) was reproduced by thread occlusion, and then reperfused for 3h, 6h, 24h, 72h respectively after 2h of ischemia. Nissl staining was used to observe the pathological changes and characteristics of neurons. The content of CysLTs in brain tissue was detected by enzyme-linked immunosorbent assay. Results: According to animal behavioral score results, the combination of baicalin and geniposide 20mg / kg can improve cerebral ischemia 2h reperfusion 6h, 24h nerve injury caused by behavioral abnormalities; 40mg / kg can improve rat brain According to the results of CysLTs in brain tissue, the optimal treatment time window and dose were ischemia reperfusion 24h, 20mg / kg after cerebral ischemia for 2h, cerebral ischemia According to the observation of pathological damage of brain tissue, the optimal treatment time window and dose were respectively reperfusion 24h, 20mg / kg at 2h after cerebral ischemia, reperfusion 72h 40h after cerebral ischemia 2h mg / kg. Conclusion: Based on the comprehensive evaluation of the principles of minimization of dosage and the maximization of treatment time window, according to animal behavior score, CysL Ts in brain tissue and pathological observation, baicalin and geniposide were used to treat cerebral ischemia-reperfusion injury in rats The best treatment time window and dose of cerebral ischemia 2h reperfusion 24 ~ 72h, 20 ~ 40mg / kg.