芪仙通络方及其拆方对脑梗死大鼠神经功能及神经营养因子表达的影响

Comparative Study on the Effects of Qixian Tongluo Formula and Its Disassembled Prescriptions on Neurological Function and Expression of Neurotrophic Factors in Rats with Cerebral Infarction

目的比较芪仙通络方及其拆方对脑梗死大鼠神经功能、梗死周边区域神经元及神经纤维损伤修复以及神经营养因子表达影响的差异。方法线栓法复制大脑中动脉栓塞(MCAO)大鼠模型,随机分为假手术组、模型组、芪仙通络全方组(补肾活血、益气温阳药)、拆方1组(补肾活血药)、拆方2组(益气温阳药)及胞磷胆碱组,造模后第3天开始灌胃给药,连续干预12 d,分别于造模后第3天、第7天、第14天采用改良大鼠神经功能缺损评分(mNSS)评定大鼠神经功能,造模后第14天采用尼氏染色和镀银染色分别观察梗死周边区域神经元和神经纤维病理形态,采用免疫组化检测脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)以及神经生长因子(NGF)的表达。结果与模型组比较,各给药组(第7天、第14天)mNSS均显著降低(P<0.01),神经元及神经纤维病理形态(第14天)明显改善(P<0.01),BDNF、GDNF以及NGF表达(第14天)显著上调(P<0.01);与拆方1组、拆方2组及胞磷胆碱组分别比较,芪仙通络全方组在造模后第7天、第14天受损神经功能恢复、造模后第14天神经元及神经纤维病理形态改善以及BDNF、GDNF、NGF表达增加效果均最优(P<0.05)。结论芪仙通络方及其拆方能促进脑梗死大鼠神经功能恢复,其机制可能与上调脑内神经营养因子BDNF、GDNF以及NGF表达,进而修复缺血损伤神经元及神经纤维有关,其中以全方组作用最佳。

Objective:To compare the effects of Qixian Tongluo Formula and its disassembled prescription on neurological function,repair of injured neuron and nerve fiber as well as expression of neurotrophic factors in rats with cerebral infarction.Methods:The rat model caused by middle cerebral artery occlusion was established by thread occlusion.The rats were randomly divided into the sham operation group,model group,Qixian Tongluo whole prescription group,Qixian Tongluo disassembled prescription group 1(tonifying kidney and activating blood circulation drug),Qixian Tongluo disassembled prescription group 2(benefiting qi and warming yang drug)and citicoline group.The rats were given intragastric administration on the 3rd day after the establishment of the model,and intervened continuously for 12 days.The mNSS was used to evaluate neurological function of the rats on the 3rd,7th and 14th day after modeling.Nissl staining and silver-plated staining were used to observe the pathological morphology of neurons and nerve fibers at the peri-infarct region,and the expressions of BDNF,GDNF and NGF were detected by immunohistochemistry.Results:Compared with the model group,the mNSS in all treatment groups(day 7 and day 14)were significantly decreased(P<0.01),the pathological morphology of neurons and nerve fibers(day 14)were significantly improved(P<0.01),the expressions of BDNF,GDNF and NGF were significantly up-regulated(P<0.01).Compared with group 1,group 2 and citicoline group,Qixian Tongluo whole prescription group had the best results in the recovery of injured neurological function on the 7th and 14th day,and the pathomorphology of neurons and nerve fibers,as well as the expression of BDNF,GDNF and NGF had the best improvement on the 14th day after modeling(P<0.05).Conclusion:Qixian Tongluo Formula and its disassembled prescriptions can promote the recovery of neurological function in rats with cerebral infarction,and its mechanism may be related to up-regulating the expression of neurotrophic factors BDNF,GDNF and NGF in the brain,and then repairing the injured neurons and nerve fibers,of which the whole prescription group has the best effect.