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目的探讨补阳还五汤对脑缺血再灌注保护作用及可能机制。方法 188只雄性蒙古沙鼠随机分成对照组、模型组、补阳还五汤高、低剂量组,根据Kirino方法制作沙鼠前脑缺血模型;免疫组化和免疫印迹法检测海马区磷酸化p38有丝分裂原活化蛋白激酶(MAPK)表达,原位缺口末端标记法(TUNEL)检测凋亡细胞,八臂迷宫测试法测试动物学习记忆功能。结果沙鼠脑缺血1、6 h,1、3 d后,海马磷酸化p38 MAPK表达水平分别为(1.85±0.86)、(4.40±1.26)、(6.70±1.87)、(5.67±1.58),与对照组比较,明显增高(P<0.05);脑缺血6 h,1、3、7 d后,凋亡神经细胞数分别为(9.60±2.69)、(12.68±2.99)、(16.94±3.92)、(25.82±4.61)个/视野,明显高于对照组(P<0.05);八臂迷宫结果显示,动物总错误次数、重复错误次数增多;高剂量补阳还五汤组磷酸p38 MAPK蛋白表达量及神经细胞凋亡数量与模型组比较明显下降(P<0.05);动物学习记忆功能指标总错误次数、重复错误次数明显低于模型组(P<0.05)。结论补阳还五汤可改善脑缺血所致认知功能损伤,与抑制p38 MAPK活化,减少神经细胞凋亡有关。
Objective To explore the protective effect of Buyang Huanwu decoction on cerebral ischemia-reperfusion and its possible mechanism. Methods 188 Mongolian gerbils were randomly divided into control group, model group and Buyang Huanwu decoction high and low dose groups. The forebrain ischemia model was made according to Kirino’s method. The phosphorylation of hippocampus was detected by immunohistochemistry and Western blotting p38 mitogen-activated protein kinase (MAPK), apoptotic cells were detected by TUNEL, and the learning and memory function was tested by eight-arm maze test. Results The phosphorylation of p38 MAPK in hippocampus was (1.85 ± 0.86), (4.40 ± 1.26), (6.70 ± 1.87), (5.67 ± 1.58), respectively Compared with the control group, the number of apoptotic neurons in the cerebral ischemia group was (9.60 ± 2.69), (12.68 ± 2.99), (16.94 ± 3.92 ), (25.82 ± 4.61) / visual fields, which were significantly higher than those in the control group (P <0.05). The results of the eight-arm maze showed that the total number of errors and the number of repeated errors in the animals increased. (P <0.05). The total number of error and repetition error of learning and memory function of animals was significantly lower than that of the model group (P <0.05). Conclusion Buyang Huanwu decoction can improve the damage of cognitive function induced by cerebral ischemia, and inhibit the activation of p38 MAPK and decrease the apoptosis of nerve cells.