高剂量异丙酚腹腔注射对阿尔茨海默病模型大鼠学习记忆能力的改善作用及其机制  

Effect of intraperitoneal injection of high-does propofol on learning and memory ability of Alzheimer's disease model rats and its mechanism

作　　者：宋云飞 SONG Yunfei(The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China)

机构地区：[1]辽宁中医药大学附属医院,沈阳110032

出　　处：《山东医药》2020年第9期10-13,共4页Shandong Medical Journal

摘　　要：目的观察高剂量异丙酚(PPF)腹腔注射对阿尔茨海默病(AD)模型大鼠学习记忆能力的改善作用,并探讨其机制。方法D-半乳糖(D-gal)腹腔注射联合三氯化铝(AlCl3)灌胃制备AD模型大鼠,随机分为模型组、多奈哌齐组、PPF低剂量组、PPF高剂量组,多奈哌齐组腹腔注射多奈哌齐,PPF低剂量组腹腔注射50 mg/kg的PPF,PPF高剂量组腹腔注射100 mg/kg的PPF,模型组腹腔注射等体积生理盐水。另选取6只正常SD大鼠为空白对照组。采用Morris水迷宫实验评估各组大鼠学习记忆能力;采用Western blotting法检测各组大鼠海马组织中β-淀粉样蛋白(Aβ蛋白)和磷酸化NF-κB(p-NF-κB)蛋白;采用比色法检测各组大鼠海马组织中AchE活力;采用ELISA法检测各组大鼠海马组织中IL-1β、IL-6和TNF-α蛋白。结果与空白对照组相比,模型组大鼠的学习记忆能力降低,海马组织中Aβ蛋白增多,AchE活力升高,p-NF-κB、IL-1β、IL-6和TNF-α蛋白水平升高;与模型组相比,多奈哌齐组、PPF低剂量组、PPF高剂量组大鼠的学习记忆能力提高,海马组织中Aβ蛋白减少,AchE活力下降,p-NF-κB、IL-1β、IL-6和TNF-α蛋白水平下降,且PPF高剂量组、多奈哌齐组的治疗效果无差异,均高于PPF低剂量组。结论高剂量PPF腹腔注射可显著改善AD模型大鼠的学习记忆能力,其机制可能与抑制海马组织中Aβ蛋白沉积、增强胆碱能功能、抑制NF-κB蛋白磷酸化、减轻脑内炎症反应有关。Objective To investigate the effect of intraperitoneal injection of high-dose propofol(PPF)on learning and memory ability of Alzheimer's disease(AD)model rats and to explore its mechanism.Methods AD model rats were established by intraperitoneal injection of D-galactose(D-gal)and gavage of aluminum trichloride(AlCl3).They were randomly divided into the model group,donepezil group,low-dose PPF group,and high-dose PPF group.AD model rats in the donepezil group was intraperitoneally injected with donepezil,the low-dose PPF group with 50 mg/kg PPF,the high-dose PPF group with 100 mg/kg PPF,and the model group with equal volume of normal saline.Six normal SD rats were selected as the control group.Morris water maze test was used to evaluate learning and memory ability of rats in each group;Western blotting was used to detectβ-amyloid protein(Aβprotein)and phosphorylated NF-κB(p-NF-κB)protein in hippocampus of rats in each group;colorimetric method was used to detect AchE activity in hippocampus of rats in each group;ELISA was used to detect IL-1β,IL-6 and TNF-αprotein in hippocampus of rats in each group.Results Compared with the control group,the learning and memory ability decreased,Aβprotein increased,AchE activity increased,p-NF-κB,IL-1β,IL-6 and TNF-αprotein levels increased in the model group.Compared with the model group,the learning and memory ability increased,Aβprotein decreased,AchE activity decreased,and the levels of p-NF-κB,IL-1β,IL-6,and TNF-αprotein decreased in the donepezil group,the low-dose PPF group,and the high-dose PPF group;there was no difference between the high-dose PPF group and donepezil group,and both of them were higher than the low-dose PPF group.Conclusions Intraperitoneal injection of high-dose PPF can significantly improve the learning and memory ability of AD model rats.The mechanism may be related to the inhibition of Aβprotein deposition in hippocampus,the enhancement of cholinergic function,the inhibition of NF-κB protein phosphorylation,and the reduction of infla

关 键 词：异丙酚 阿尔茨海默病 学习记忆能力 Β-淀粉样蛋白 乙酰胆碱酯酶 炎症因子 NF-κB信号通路 动物实验 

分 类 号：R285.5[医药卫生—中药学]