参仙汤对多发性脑梗死性痴呆大鼠学习记忆能力的干预效应

背景解放军总医院自行研制的参仙汤方,经临床初步观察28例脑血管性痴呆患者,其智能量表分值有明显提高.目的观察中药复方参仙汤对多发性脑梗死性痴呆大鼠学习记忆的影响,并对其抗自由基损伤能力进行分析.设计双盲随机对照实验.单位解放军总医院中医科.材料实验于1997-05/12在解放军总医院中医科完成.选取3个月龄SD大白鼠72只,随机分为6组正常对照组,痴呆模型组,阿尼西坦组,参仙汤30,15,7.5/g(kg·d)剂量组,12只/组.参仙汤由人参、仙灵脾、何首乌、地龙等组成.按传统煎药法煎取药液,以恒温水浴锅分别浓缩成含生药2.0,1.0,0.5g/mL.方法参仙汤30,15,7.5g/(kg·d)剂量组分别按成人每公斤体质量剂量的20,10,5倍给予参仙汤灌胃,剂量分别为生药30,15,7.5g/(kg·d);阿尼西坦组给予100 mg/(kg·d)阿尼西坦灌胃;痴呆模型组和正常对照组分别灌以等量生理盐水.连续给药7 d,第7天给药后1h开始造模.除正常对照组外,其余各组均造模.左心室注射液体石蜡栓子0.25 mL/kg,建立多发性脑梗死模型.造模后继续给药至42 d.然后采用水迷宫实验对大鼠学习记忆能力进行评估.实验结束后1h将各组大鼠脱臼处死,进行组织、脏器各项生化指标的测定.主要观察指标参仙汤对多发性脑梗死性痴呆大鼠水迷宫作业时间、作业正确次数、脏器生化指标的影响.结果实验纳入72只大鼠,操作过程中脱落9只,最后共63只大鼠进入结果分析.①参仙汤对多发性脑梗死性痴呆大鼠水迷宫作业时间的影响与痴呆模型组比较,参仙汤15,30g/(kg·d)剂量组于迷宫实验第5天均明显缩短(24.1±13.3),(14.7±6.9),(13.7±7.5)s,P均＜0.05].②参仙汤对多发性脑梗死性痴呆大鼠水迷宫作业正确次数的影响与痴呆模型组比较,参仙汤15,30g/(kg·d)剂量组于迷宫实验第5天均显著增加(1.70±2.07),(3.82±1.89),(4.36±1.75)次,P＜0.01].③参仙汤对多发性脑梗死性痴呆大鼠超氧化物歧化酶的影响与痴呆模型组比较,参仙汤15,30g/(kg·d)剂量组脑、肝组织超氧化物歧化酶活力均显著增加(127.2±7.2),(171.3±11.5),(181.7±10.9)μkat/kg,P＜0.001;(168.0±23.7),(185.8±14.9),(200.7±15.4)μkat/kg,P＜0.05,P＜0.01].④参仙汤对多发性脑梗死性痴呆大鼠丙二醛含量的影响与痴呆模型组比较,参仙汤15,30g/(kg·d)剂量组脑、肝组织丙二醛含量均明显降低(296.0±37.8),(204.6±43.5),(197.3±43.5)nmol/g,P＜0.001;(238.9±60.8),(160.3±29.4),(152.1±34.4)nmol/g,P＜0.01].⑤参仙汤对多发性脑梗死性痴呆大鼠丙二醛含量的影响与痴呆模型组比较,参仙汤15,30g/(kg·d)剂量组脑、肝组织脂褐素含量均明显降低(10.88±1.95),(6.35±1.55),(5.85±1.23)μg/g,P＜0.001;(7.17±1.75),(4.38±1.54),(3.69±1.24)μg/g,P＜0.01].结论中药参仙汤具有提高多发性脑梗死性痴呆大鼠脏器组织超氧化物歧化酶活力、减轻脂质过氧化反应、降低组织丙二醛和脂褐素含量的作用,通过减轻脑缺血再灌注的自由基损伤,从而改善多发性脑梗死性痴呆大鼠的学习记忆能力.

Intervention effect of shenxian tang on the learning and memory power of rats with multiple cerebral infarction dementia

BACKGROUND: Shenxian tang developed in General Hospital of Chinese PLA can obviously raise the intelligence scale through clinical observation of 28 cases of patients with cerebrovascular dementia.OBJECTIVE: To investigate the effect of traditional Chinese drug compound shenxian tang on the learning and memory power of rats with multiple cerebral infarction dementia, and analyze its resisting power to free radical injury.DESIGN: A double-blink and randomized controlled trial.SETTING: Department of Traditional Chinese Medicine of General Hospital of Chinese PLA.MATERIALS: The experiment was completed from May to December 1997 at the Department of Department of Traditional Chinese Medicine of The rats in aniracetam group were by gavage given aniracetam 100 mg/age given normal saline of the same volume. The administration was consecutively give for 7 days, one hour after the last administration, the models (except for normal control group) were built up: Liquid paraffin 0.25 mL/kg was injected into the left ventricle of the rat for establishment of multiple cerebral infarction dementia model. After built up of the model, the administration was continued until to the forty second day. Then the learning and memory power of the rat was assayed by using water maze test. One hour after the test the rats were put to death by dislocation for measurement of biochemical indexes.MAIN OUTCOME MEASURES: The effects of shenxian tang on the working time and correct times of working in the water maze, and biochemical indexes of the viscera of the rats with multiple cerebral infarction dementia.RESULTS: In the trial 72 rats were involved, 9 rats were lost during the shenxian tang on the working time in the water maze of the rats with multiple cerebral infarction dementia: Compared with dementia model group,ly shortened on the fifth day of water maze test (24.1±13.3) s, (14.7±6.9) s,times of working in the water maze of the rats with multiple cerebral infarction dementia: Compared with dementia model group, the correct times the fifth day of water maze test (1.70±2.07) times, (3.82±1.89) times,tivity of superoxide dismutase (SOD) of the rats with multiple cerebral infarction dementia: Compared with dementia model group, the activity of obviously increased (127.2±7.2), (171.3±11.5), (181.7±10.9) μkat/kg,P ＜ 0.001; (168.0±23.7), (185.8±14.9), (200.7±15.4) tμkat/kg, P ＜ 0.05,hyde (MDA) of the rats with multiple cerebral infarction dementia: Compared with dementia model group, the content of MDA of the brain and liv(296.0±37.8), (204.6±43.5), (197.3±43.5) nmol/g, P ＜ 0.001; (238.9±60.8),tang on the content of lipofuscin of the rats with multiple cerebral infarction dementia: Compared with dementia model group, the content of lipoobviously decreased (10.88±1.95), (6.35±1.55), (5.85±1.23) μg/g, P ＜0.001; (7.17±1.75), (4.38±1.54), (3.69±1.24) μ g/g, P ＜ 0.01].CONCLUSION: Shenxian tang a traditional Chinese drug compound, was of the effects of raising the activity of SOD, reducing lipid peroxidation, increasing the contents of MDA and lipofuscin of the organic tissues of rats with multiple cerebral infarction dementia; it could also reduce the free radical injury during ischemia-reperfusion process sp as to improve the power of learning and memory of rats with multiple cerebral infarction dementia.