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目的观察柴胡细辛汤加减对颅脑损伤模型大鼠认知功能和神经功能缺损的作用及其可能机制。方法将89只SD大鼠随机分为假手术组16只,模型组、阳性对照组和中药低剂量组各18只,中药高剂量组19只,除假手术组外其余各组建立控制性皮层冲击损伤模型。造模次日阳性对照组予安理申片0.45 g/(kg·d),中药低、高剂量组分别给予柴胡细辛汤加减方6.5、13 g生药/(kg·d),假手术组、模型组予等体积双蒸水,各组灌胃4周。比较各组大鼠认知功能(水迷宫测试)、神经功能缺损评分(m NSS)、脑组织病理与海马CA1区超微结构,并检测CA1区脑源性神经生长因子(BDNF)、突触素1(SYN1)蛋白表达。结果各组在造模后0、3、7天时m NSS评分较假手术组均明显升高(P<0.01),中药高剂量组在第7、28天时m NSS评分较模型组降低,中药低剂量组在28天时亦低于模型组(P<0.05或P<0.01)。水迷宫测试中,各给药组逃避潜伏期时间较模型组减少(P<0.05或P<0.01)。各给药组损伤海马区病理形态学显示优于模型组,中药高、低剂量组能够改善海马CA1区受损的神经元、线粒体和突触的超微结构。中药高剂量组BDNF表达明显高于模型组和阳性对照组,中药高剂量组SYN1表达高于模型组(P<0.01)。结论柴胡细辛汤加减能够改善颅脑损伤模型大鼠认知功能及其神经功能缺损,其机制可能是提高海马CA1区BDNF、SYN1的表达以促进损伤的神经元修复与突触重塑,改善海马CA1区超微结构。
Objective To observe the effect and its possible mechanism of Chaihu Xixin Decoction on cognitive function and neurological deficit in brain injury model rats. Methods Totally 89 SD rats were randomly divided into sham operation group (n = 16), model group, positive control group and traditional Chinese medicine low dose group (n = 18), and Chinese medicine high dose group (n = 19) Impact damage model. The positive control group was given 0.45 g / (kg · d) of Amnion tablets on the next day. The rats in the low and high dose groups were given 6.5, 13 g crude drug / (kg · d) respectively. The sham operation group , The model group was given an equal volume of double distilled water, each group gavage for 4 weeks. The cognitive function (water maze test), neurological deficit score (m NSS), brain histopathology and the ultrastructure of hippocampal CA1 region of rats in each group were compared. The expressions of brain derived neurotrophic factor (BDNF), synapse Sup1 (SYN1) protein expression. Results The scores of m NSS at 0, 3 and 7 days were significantly higher than those in sham-operated group (P <0.01). The m-NSS score of Chinese medicine high-dose group was lower than that of model group on the 7th and 28th days The dosage group was also lower than the model group at 28 days (P <0.05 or P <0.01). In the water maze test, the escape latency of each administration group was shorter than that of the model group (P <0.05 or P <0.01). The histopathology of the injured hippocampus in each administration group was better than the model group. The high and low doses of traditional Chinese medicine group could improve the ultrastructure of neurons, mitochondria and synapse in the hippocampus CA1 area. The expression of BDNF in high-dose group was significantly higher than that in model group and positive control group. The SYN1 expression in high-dose group was higher than that in model group (P <0.01). Conclusion The addition and subtraction of Chaihu Xixin Decoction can improve the cognitive function and neurological deficits of rats with craniocerebral injury. Its mechanism may be to increase the expression of BDNF and SYN1 in hippocampal CA1 area to promote the repair of neurons and synaptic remodeling, Improve the ultrastructure of hippocampal CA1 area.