参乌胶囊对糖尿病复合脑缺血模型大鼠学习记忆功能和细胞凋亡相关蛋白表达的影响

 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和细胞凋亡相关蛋白表达的干预作用。方法　采用在大鼠腹腔注射链脲佐菌素 (streptozotocin ,STZ ,6 0mg·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 ,用Westernblotting法对大鼠海马中的细胞凋亡相关蛋白进行测试。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63.4%;而参乌胶囊小剂量组较模型组动物缩短61.3%,参乌胶囊中剂量组较模型组动物缩短75.3%(P <0.01) ;Bcl-2在模型组表达明显比对照组少,而在参乌胶囊中剂量组和大剂量组中比模型组表达多 ;caspase-3在模型组中的表达明显比对照组多 ,caspase-3和Bax在参乌胶囊中剂量组和大剂量组中的表达明显比模型组少。结论　本实验建立的糖尿病脑病动物模型可使大鼠存在认知功能障碍 ;糖尿病脑病发生机制与神经元细胞凋亡有关 ;参乌胶囊有改善模型大鼠的学习记忆功能和抑制神经元细胞凋亡的功能。

Study on the effects of Shenwu capsule on the cognitive function and apoptosis protein in ischemic-diabetic com-pound model rats

OBJECTIVE To explore the mechanism of diabetic encephalopathy and the effect of Chinese patent medicine Shenwu capsule on the cognitive function and apoptosis in ischemic-diabetic model rats.METHODS The compound model of Wistar rats was duplicated with streptozotocin (STZ) injection (60 mg·kg ^-1) once intraperitoneally and transient occlusion of both carotid arteries. After 30 days treatment with Shenwu capsule of high, middle and low dosages, the ability of learning and memory function were tested by water maze. The expressions of apoptosis protein Bax,Bcl-2 and Caspase-3 were evaluated by Western blotting in rat hippocampus.RESULTS After 4 consecutive days of training, the swimming time to platform in ischemic-diabetic compound model rats was 63.4% longer than that of control group (P<0.05), that of Shenwu groups was shorter than model 61.3% and 75.3% for low and middle dosage respectively(P<0.05). Western blot analysis revealed that the expression of Bax in the middle and high dosage reduced significantly compared with model rats; Bcl-2 protein expression was lower in the model group than that of controls, while that of the Shenwu groups were higher than model rats; Caspase-3 in the model group increased compared with controls, whereas those in the middle and high dosage reduced.CONCLUSION On the basis of causing diabetes mellitus with STZ, executing transient occlusion of both carotid arteries built diabetic encephalopathy rat model effectively and quickly. The model rats had cognitive disfunction. Cell apoptosis in neurons is one of the factors of the mechanism of diaetic encephalopathy.Shenwu capsule improved the learning and memory function and inhibited apoptosis in rats.