黄芩苷和牛磺酸对阿尔茨海默病大鼠保护作用的最佳配比研究

摘要

Objective To observe the best compatibility proportion and action mode of protective effects of combined baicalin and taurine in Alzheimer’s disease (AD) model.Methods Aβ1-42 was injected through lateral ventricles to establish AD rat models. SD rats were randomly divided into sham-operation group, model group, aricept group, combined baicalin and taurine in different proportions group. Administration groups were treated with different medicines, while sham-operation group and model group were treated with the same amount of normal saline for 40 days. The step-through latency and the times of mistakes were detected through step-through test;the escape latent and the times of crossing target quadrant were detected through Morris water maze. Furthermore, the human neuroblastoma SH-SY5Y cells were induced by 5 µmol/L Aβ1-42 for establishing a cellular AD model. The AD cellular model was treated with baicalin and taurine compatibility in different proportions for 48 hours. Then the rate of cell viability was detected by MTT assay, and the median effective concentration (EC50) and combination index were calculated. Results Baicalin and taurine in 2∶1 and 1∶1 proportion groups can significantly improve learning and memory ability in AD rats (P<0.05,P<0.01). The EC50 were 2.110 µmol/L and 0.422 µmol/L, respectively. The combination index was 0.308.Conclusion Baicalin combined with taurine exhibit synergetic protective effects in AD rats induced by Aβ1-42. The optimal compatibility proportion of baicalin and taurine is 2∶1, and EC50 is 0.279 µmol/L.%目的：探讨黄芩苷和牛磺酸对β-淀粉样蛋白(Aβ1-42)诱导的阿尔茨海默病(Alzheimer's disease,AD)大鼠保护作用的最佳配伍比例及作用方式。方法将SD雄性大鼠随机分为对照组、模型组、阳性药(安理申)组、黄芩苷和牛磺酸不同比例配伍组,除对照组外,采用侧脑室注射 Aβ1-42方法建立 AD 大鼠模型,各给药组给予相应药物灌胃,对照组及模型组给予等量生理盐水,连续给药40 d。采用避暗实验检测大鼠步入潜伏期和错误次数；应用Morris水迷宫实验检测大鼠逃避潜伏期和穿越目标区域次数。同时,使用5µmol/L Aβ1-42诱导神经母细胞瘤SH-SY5Y细胞建立AD细胞模型,使用不同比例黄芩苷和牛磺酸配伍干预AD细胞模型48 h,采用 MTT 法检测细胞存活率,计算药物半数有效剂量(EC50)及联合指数。结果黄芩苷和牛磺酸2∶1及1∶1配伍组均能明显改善AD大鼠学习和记忆能力(P＜0.05,P＜0.01)。黄芩苷、牛磺酸EC50为2.11、0.422µmol/L,联合指数为0.308。结论黄芩苷和牛磺酸配伍对Aβ1-42诱导的AD大鼠具有协同保护作用,最佳配伍比例为2∶1,EC50为0.279µmol/L。