大黄酚联合多奈哌齐对阿尔茨海默病模型大鼠的防治作用

Effects of Chrysophanol and Donepezil on Alzheimer's Model Rats

摘要:

目的: 建立阿尔茨海默病(Alzheimer's disease,AD)大鼠模型,观察大黄酚联合多奈哌齐对 AD大鼠的学习记忆能力、乙酰胆碱转移酶(ChAT)含量、乙酰胆碱酯酶(ChE)含量、过氧化物酶(POD)活力、总抗氧化能力(T-AOC)的影响,探讨大黄酚联合多奈哌齐对 AD 的防治作用. 方法: 用 D-半乳糖和三氯化铝制备 AD 大鼠模型,连续 90 d.将大鼠随机分为正常组,模型组,大黄酚组(0.14 mg·kg^-1),多奈哌齐组(0.33 mg·kg^-1),大黄酚联合多奈哌不同剂量组(大黄酚0.14 mg·kg^-1+多奈哌齐0.33 mg·kg^-1组,大黄酚0.07 mg·kg^-1+多奈哌齐0.66 mg·kg^-1组,大黄酚0.28 mg·kg^-1 +多奈哌齐0.17 mg·kg^-1组).从造模的第20天开始,给药组ig给予相应剂量药物,模型组ig给予等量生理盐水,连续70 d.给药结束后,通过Morris水迷宫观察各组大鼠学习记忆能力;观察各组大鼠脑组织ChE,ChAT,POD,T-AOC. 结果: 与模型组比较大黄酚,多奈哌齐及大黄酚联合多奈哌齐均能缩短AD模型大鼠水迷宫逃避潜伏期(P<0.05, P<0.01),增加穿越平台次数(P<0.05,P<0.01);其中,大黄酚联合多奈哌齐(大黄酚0.028 mg·kg^-1 +多奈哌齐0.17 mg·kg^-1)组大鼠与大黄酚,多奈哌齐组比较,逃避潜伏期显著缩短(P<0.05),穿越平台次数显著增加(P<0.05).与模型组比较,大黄酚,多奈哌齐及大黄酚联合多奈哌齐组大鼠ChAT,POD,T-AOC活性升高(P<0.05),ChE活性降低(P<0.05);其中,大黄酚联合多奈哌齐(大黄酚0.028 mg·kg^-1+多奈哌齐0.17 mg·kg^-1)组大鼠ChAT,POD,T-AOC活性升高特别显著(P<0.01). 结论: 大黄酚与多奈哌齐联合对改善AD大鼠的学习记忆能力, 具有协同作用.其作用与二者剂量比有关,大黄酚作为主药,辅以多奈哌齐对阿尔茨海默病的防治作用较好.

Abstract:

Objective: To observe the effect of chrysophanol and donepezil on the ability of learning and memory and the activity of choline acetyltransterase (ChE), cholinesterase (ChAT), peroxidase (POD) and total antioxidant capacity (T-AOC) in the AD rat's brain, and then discuss the preventive and treatment effect of chrysophanol and donepezi on AD rat. Method: The AD model was produced by injecting D-galactose and AlCl₃ intraperitoneally for 90 days. Rats were randomly divided into normal group, model group, chrysophanol group (0.14 mg·kg^-1), donepezil group (0.33 mg·kg^-1), chrysophanol joint donepezil groups (chrysophanol 0.14 mg·kg^-1+donepezil 0.33 mg·kg^-1, chrysophanol 0.07 mg·kg^-1+donepezil 0.66 mg·kg^-1, chrysophanol 0.28 mg·kg^-1+donepezil 0.17 mg·kg^-1). From the 20^th day of D-galactose and AlCl₃ intraperitoneal injection, chrysophanol and Donepezil were intragastric administrated respectively for 70 days. The learning and memory ability of each group rats were observed by Morris water maze. The activity of ChE, ChAT, POD and T-AOC in the AD rat's brain were determinated. Result: Rats intragastric administration with chrysophanol, donepezil and chrysophanol joint donepezil had shorter latency(P<0.05, P<0.01)and more numbers through the platform (P<0.05, P<0.01). Compared with chrysophanol group and donepezil group, rats in chrysophanol joint donepezil group (chrysophanol 0.28 mg·kg^-1+donepezil 0.17 mg·kg^-1) had shorter latency(P<0.05)and more numbers through the platform (P<0.05). Compared with the model group, the activity of ChAT, POD and T-AOC in the chrysophanol group, donepezil group and chrysophanol joint donepezil groups rat's brain elevated significantly(P<0.05), those of the chrysophanol joint donepezil group(chrysophanol 0.28 mg·kg^-1+donepezil 0.17 mg·kg^-1) elevated significantly(P<0.01). The activity of ChE reduced(P<0.05). Conclusion: Chrysophanol joint donepezil can improve the learning and memory ability of AD rats, their effects were collaborative. The effect is associated with their doses. Chrysophanol supplemented by donepezil may get a better effect on Alzheimer's disease.