参乌胶囊对糖尿病复合脑缺血模型大鼠学习记忆功能和海马突触功能的影响

Shenwu capsule affects cognitive function and hippocampus LTP in diabetic and brain ischemia rat

目的研究糖尿病性脑病病变机制以及参乌胶囊对糖尿病复合脑缺血模型大鼠学习记忆功能干预作用。方法采用在大鼠腹腔注射链脲佐菌素(streptozotocin,STZ)(60mg·kg-1)引起糖尿病的基础上,再行双侧颈动脉缺血再灌手术建立糖尿病脑病变动物模型。经参乌胶囊小剂量(0.45g·kg-1·d-1)、中剂量(0.9g·kg-1·d-1)和大剂量(1.8g·kg-1·d-1)灌胃治疗30d后,用Morris水迷宫实验对动物行为学进行评价以及用玻璃微电极记录诱发的锥体细胞群峰电位测定大鼠海马脑片长时程增强效应(longtermpotentiation,LTP)。结果糖尿病复合脑缺血模型大鼠到达站台游动时间比正常对照组增长115.3%(P<0.01);而参乌胶囊小、中、大剂量组较模型组动物分别缩短59.0%(P<0.01),75.2%(P<0.01)和38.9%(P<0.05);复合模型大鼠在高频刺激后,不论波幅还是斜率的增强都不如正常对照组明显,表明了突触增强能力减退(P<0.05)。参乌胶囊治疗组在高频刺激后PS波幅、斜率较糖尿病复合脑缺血模型组有明显增强(P<0.05)。结论糖尿病复合脑缺血模型大鼠存在认知功能障碍和海马突触可塑性功能减弱;参乌胶囊有改善糖尿病复合脑缺血模型大鼠的学习记忆功能和突触可塑性功能。单纯糖尿病模型和单纯脑缺血模型在造摸4周后不足以引起大鼠认知功能和突触可塑性功能的改变。

OBJECTIVE To explore the mechanism of diabetic encephalopathy and the effect of cognitive function of Chinese patent medicine Shenwu capsule. METHODS The diabetic encephalopathy model of rats was established by intraperitoneal injection of 60 mg·kg^-1 streptozotocin （STZ） followed by bilateral carotid artery occlusion after 3 d STZ injection. After 30 d treatment by 3 doses of Shenwu capsule （low, middle and high dose）, the ability of learning and memorying function were tested by Morris water maze. Hippocampal synaptic plasticity was evaluated by long term potentiation （LTP） .RESULTS On the fifth day the swimming time to reach the platform was increased by 115.3% in diabetic-ischemic model rats （P〈 0.01）. The swimming time of Shenwu capsule groups at low, middle and high dose were apparently shorter than that of model rats 59.0 % （ P 〈 0.01 ）, 75.2 % （ P〈 0.01 ） and 38.9 % （ P 〈 0.05）, respectively. In LTP test of hippocampal slices, both amplitude and slope in diabetic-ischemic model rats were apparently reduced compared with those in controls after high-frequency （100 Hz） stimulation（ P 〈 0.05）, whereas they were increased in the Shenwu group compared with the combined models（ P 〈 0.05）. CONCLUSlON On the basis of diabetes meUitus using SIZ, executing transient occlusion of bilateral carotid arteries effectively and quickly built diabetic encephalopathy rat model, diabetic-ischemic model rats had cognitive disfuncfion and hippocampus LTP impairment. Shenwu capsule improved the cognifive function and strengthened LTP in diabetic-isehemic model rats.