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目的:观察中药复方颐神养脑胶囊(YSYN)对大鼠多发性脑梗死痴呆(MID)的疗效及作用机制。方法:3月龄SD大鼠90只,于左侧颈外动脉注入复合血栓诱导剂,复制多发性脑梗死痴呆模型,动物随机分为模型组、YSYN高剂量组(960 mg·kg-1)、YSYN中剂量组(480 mg·kg-1)、YSYN低剂量组(240 mg·kg-1)、西药阳性组(易倍申)(0.5 mg·kg-1)以及YSYN合西药阳性药组(480 mg·kg-1+0.5 mg·kg-1),另设10只动物为假手术组,造模后第3天,各组均以10 mL·kg-1灌胃给药,1次/d,连续4周,模型组和假手术组给予等量蒸馏水。采用Morris水迷宫法进行学习记忆测试;采用酶联免疫法测定海马组织去甲肾上腺素(NE)水平;采用比色法测定海马组织乙酰胆碱酯酶(AchE)、乙酰胆碱转移酶(CHAT)和谷胱甘肽过氧化物酶(GSH-Px)水平。结果:与假手术组比较,模型组大鼠学习记忆能力显著降低(P<0.05,P<0.01),海马组织AchE含量显著升高(P<0.05),海马组织CHAT、NE以及GSH-Px含量显著降低(P<0.01);与模型组比较,YSYN能够显著提高多发性脑梗死痴呆大鼠学习记忆能力(P<0.05);显著降低多发性脑梗死痴呆大鼠海马组织AchE含量,提高多发性脑梗死痴呆大鼠海马组织CHAT、NE及GSH-Px含量(P<0.05,P<0.01)。结论:YSYN对MID具有良好的保护作用,其作用机制可能是通过调节海马组织内去甲肾上腺素、乙酰胆碱及谷胱甘肽的活性来实现的。
Objective: To observe the curative effect and mechanism of Yishen Yangao Nao Capsule (YSYN) on dementia (MID) in rats with multiple cerebral infarction. Methods: Ninety-three-month-old Sprague-Dawley rats were injected with thrombosis inducer into the left external carotid artery to establish a model of dementia with multiple cerebral infarction. The animals were randomly divided into model group, high dose YSYN group (960 mg · kg -1) , YSYN middle dose group (480 mg · kg -1), YSYN low dose group (240 mg · kg -1), Western medicine positive group (0.5 mg · kg -1) and YSYN western medicine group (480 mg · kg -1 + 0.5 mg · kg -1). Another 10 animals were sham-operated group. On the 3rd day after model establishment, each group was given gavage with 10 mL · kg -1, / d for 4 weeks, the model group and sham operation group were given equal volume of distilled water. The Morris water maze test was used to test the learning and memory. The level of norepinephrine (NE) in the hippocampus was detected by enzyme-linked immunosorbent assay (ELISA). The levels of acetylcholinesterase (AchE), acetylcholinesterase (CHAT) Glycopeptide peroxidase (GSH-Px) levels. Results: Compared with the sham operation group, the learning and memory abilities in the model group were significantly decreased (P <0.05, P <0.01), the AchE content in the hippocampus was significantly increased (P <0.05), the levels of CHAT, NE and GSH-Px (P <0.01). Compared with the model group, YSYN could significantly improve the learning and memory abilities in dementia rats with multiple cerebral infarction (P <0.05), and significantly reduce the content of AchE in the hippocampus of multiple dementia rats The levels of CHAT, NE and GSH-Px in the hippocampus of dementia rats with cerebral infarction (P <0.05, P <0.01). CONCLUSION: YSYN has a good protective effect on MID. Its mechanism may be through regulating the activity of norepinephrine, acetylcholine and glutathione in the hippocampus.