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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 study the pathogenesis of diabetic encephalopathy and the effect of Shenwu capsule on the learning and memory function of diabetic rats with cerebral ischemia. Methods Diabetic brain lesions were established on the basis of intraperitoneal injection of streptozotocin (STZ) (60 mg·kg-1) to induce diabetes in rats. Shenqi capsules were intragastrically administered at low doses (0.45 g·kg-1·d-1), medium doses (0.9 g·kg-1·d-1), and large doses (1.8 g·kg-1·d-1). After 30 days of treatment, the long-term potentiation (LTP) of rat hippocampal slices was measured using the Morris water maze test to evaluate the animal behavior and the glass cell microelectrode recording the pyramidal cell population peak potential. Results Rats with diabetes mellitus combined with cerebral ischemia had a 115.3% increase in time to reach the platform (P<0.01), while the Shenwu capsule group had a 59.0% reduction in the number of rats in the small, medium, and high dose group compared with the model group (P<0.01). ), 75.2% (P<0.01) and 38.9% (P<0.05); After high-frequency stimulation in the composite model rats, the enhancement of the amplitude or slope was not as obvious as that of the normal control group, indicating that the synaptic enhancement capacity was decreased (P<0.05). <0.05). The amplitude and slope of PS amplitude in the Shenwu capsule treatment group were significantly higher than those in the diabetic combined cerebral ischemia model group (P<0.05). Conclusion Diabetic complex cerebral ischemia rats have cognitive dysfunction and decreased hippocampal synaptic plasticity; Shenwu Capsule can improve learning and memory function and synaptic plasticity in rats with diabetes mellitus and cerebral ischemia. The model of simple diabetes and the model of cerebral ischemia alone were not sufficient to induce changes in cognitive function and synaptic plasticity after 4 weeks of operation.