注射用血栓通对糖尿病模型大鼠认知障碍的作用机制研究

Effects and mechanism of Xueshuantong for injection on cognitive impairment of diabetic model rats

目的探究注射用血栓通对糖尿病模型大鼠认知障碍的作用及机制。方法用链脲佐菌素注射法制备糖尿病大鼠模型。根据血糖高低将造模成功大鼠随机分成3组:模型组(15只)和高、低2个剂量实验组(血栓通:100,50 mg·kg^(-1);各14,16只),另设正常大鼠18只为正常组。给药60 d后,水迷宫检测各组大鼠认知能力,蛋白印迹法或实时荧光定量-PCR检测大鼠海马胶质细胞中胶质纤维酸性蛋白(GFAP)、肿瘤坏死因子(TNF-α)和Cleaved caspase-3的基因或蛋白的表达量。结果正常组、模型组和低、高2个剂量实验组的穿越平台的次数(次)分别为4.06±1.00,2.88±1.26,4.44±1.71和3.19±0.91;模型组与正常组相比,差异有统计学意义(P<0.05);模型与低实验组相比,差异有统计学意义(P<0.01)。正常组、模型组和低、高2个剂量实验组的GFAP蛋白表达水平分别为1,4.05±0.57,2.03±0.16和2.18±0.39;这4组的Cleaved caspase-3蛋白水平分别为1.00±0.00,2.44±0.16,1.41±0.26和1.44±0.23;这4组的TNF-α基因表达水平分别为1.00±0.03,3.66±0.69,0.71±0.21和1.75±0.34。以上指标:模型组与正常组相比,或低、高2个剂量实验组与模型组相比,差异均有统计学意义(均P<0.01)。结论血栓通可改善糖尿病大鼠学习记忆能力,其机制与抑制胶质细胞的激活及炎症因子的表达有关。

Objective To explore the effect of Xueshuantong for injection on cognitive impairment of diabetic model rats. Methods Streptozotocin injection method was used to prepare diabetic rat models, which were randomly divided into 3 groups according to the level of blood glucose, namely model group(n=15),experimental-L(50 mg·kg^(-1) Xueshuantong, n=16),experimental-H(100 mg·kg^(-1) Xueshuantong, n=14) group. And normal rats are the normal group. After 60 d of administration, the water maze test was used to evaluate the cognitive impairment of rats. Western blotting and real time fluorescence quantitative-PCR were used to detect the expression levels of of hippocampal glial cell markers glial fibrillary acidic protein(GFAP)protein, Cleaved caspase-3 protein and tumor necrosis factor-α(TNF-α).Results The times across platform of normal group, model group, experimental-L group and experimental-H group were 4. 06 ± 1. 00,2. 88 ± 1. 26,4. 44 ± 1. 71 and 3. 19 ± 0. 91;Comparison between model group and normal group,the difference was significant( P < 0. 05);comparison between two doses experimental groups and model group,the difference was significant( all P < 0. 01). The expression of GFAP protein in the normal group,model group,experimental-L group and experimental-H group were 1,4. 05 ± 0. 57,2. 03 ± 0. 16 and 2. 18 ± 0. 39;the expression of cleaved caspase-3 protein in the 4 groups were 1. 00 ± 0. 00,2. 44 ± 0. 16,1. 41 ± 0. 26 和 1. 44 ± 0. 23;the expression of TNF-αmRNA were 1 ± 0. 03,3. 66 ± 0. 69,0. 71 ± 0. 21 and 1. 75 ± 0. 34. Comparison between model group and normal group,the difference of the factors were significant( all P < 0. 01);comparison between two doses experimental groups and model group,the difference of the factors were significant( all P < 0. 01). Conclusion Xueshuantong can improve the learning and memory ability of diabetic rats,and its mechanism is related to the inhibition of glial cell activation and the expression of inflammatory factors.