芍药苷对血管性痴呆模型大鼠乙酰胆碱酯酶及超氧化物歧化酶的影响

The effect of paeoniflorln on rat model of vascular dementia acetylcholinesterase and superoxide dismutase

目的观察芍药苷(PF)对血管性痴呆大鼠学习记忆能力及乙酰胆碱酯酶(AchE)、超氧化物歧化酶(SOD)水平的影响。方法 50只Wistar大鼠随机分为假手术组、模型组、给药组(芍药苷低剂量组12.5 mg/kg、中剂量组25 mg/kg、高剂量组50 mg/kg),每组10只。模型组与给药组采用反复夹闭双侧颈总动脉(CCA)结合腹腔注射硝普钠法造模,假手术组不阻断CCA及注射硝普钠。造模后第2天给药组予灌胃给药,模型组与假手术组给予生理盐水灌胃,每天1次,连续30 d。应用Morris水迷宫实验、跳台实验测定大鼠学习记忆能力,并比较各组AchE、SOD活性。结果(1)Morris水迷宫实验:模型组和假手术组定位航行实验中逃避潜伏期均逐渐缩短,第5天明显比第1天短(P<0.05);与假手术组比较,模型组潜伏期在各个时间点均延长,而穿过平台的次数明显减少(P<0.01);与模型组比较,给药组潜伏期呈缩短趋势,第5天比第1天短(P<0.05);穿过平台的次数明显增加(P<0.05或P<0.01)。(2)跳台实验:与假手术组比较,模型组错误次数明显增加,而潜伏期明显缩短(P<0.01);与模型组比较,3个给药组的错误次数均明显降低,潜伏期均高于模型组(P<0.05或P<0.01)。与低、中剂量组比较,高剂量组潜伏期延长更显著(P<0.01)。(3)脑组织匀浆中AchE、SOD活性:与假手术组比较,模型组AchE活性增高、SOD活性降低(P均<0.01);与模型组比较,低、中、高剂量组AchE活性明显降低、SOD活性均升高(P<0.05或P<0.01);与低剂量组相比,高剂量组AchE活性降低(P<0.05),SOD活性明显升高(P<0.01);与中剂量组相比,高剂量组SOD活性升高(P<0.05)。结论芍药苷对血管性痴呆大鼠学习记忆能力障碍有改善作用,其机制之一可能是基于抑制AchE活性,增加SOD的活性。

Objective To observe the effect of paeoniflorin（PF） on the vascular dementia rats learning and memory ability,and acetylcholinesterase（AchE）,superoxide dismutase（SOD） level.Methods Fifty Wistar rats were randomly divided into sham operation group,model group,drug group（paeoniflorin low dose group with 12.5 mg/kg,middle dose group with 25 mg/kg,high dose group with 50 mg/kg）,with 10 rats in each group.The model group and the treatment group by repeated clamping of bilateral common carotid artery（CCA） model combined with intraperitoneal injection of sodium nitroprusside,sham operation group did not block the CCA and injection of sodium nitroprusside.After second day of establish the mode,treatment group was given intragastric administration,the model group and the sham operation group were given normal saline,1 times a day,continuous 30 d.Application of Morris water maze test,step-down test the learning and memory ability of rats,and comparison of AchE,SOD activity.Results（1） Morris water maze experiment：model group and sham operation group positioning navigation test in escape latency gradually shortened,fifth days shorter than first days（P〈0.05）;compared with the sham operation group,model group were prolonged incubation at each time point,and through the platform was significantly reduced（P〈 0.01）;compared with the model group,drug group latency showed a trend of shortening,fifth days more shorter than first days（P〈0.05）;times across the platform significantly increased（P 〈 0.05 or P 〈 0.01）.（2） In step-down test：compared with the sham operation group,model group,the number of errors increased significantly,and was significantly shortened（P 0.01）;compared with the model group,the 3 groups were significandy decreased the number of errors,the latency was higher than that in the model group（P〈 0.05 orP〈 0.01）.Compared with the low,middle dose group,high dose group had significantly more prolonged latency（P〈0.01）.（3） AchE,SOD activity of brain homogenates;compared with the sham operation group,model group,AchE decreased,SOD activity increased（P〈 0.01）;compared with the model group,low,middle and high dose groups AchE activity decreased,SOD activity increased（P 〈0.05 orP 〈0.01）;compared with the low dose group,high dose group AchE activity decreased（P〈 0.05）,the activity of SOD increased significandy（P〈0.01）;compared with middle dose group,high dose group s activity of SOD increased（P〈0.05）.Conclusion Paeoniflorin improved vascular dementia rats learning and memory ability,one of the possible mechanisms is on the basis of inhibition of AchE activity to increase the activity of SOD.