银杏黄酮苷调控CIRI大鼠神经营养素信号通路的抗感染免疫机制  

Anti-infective immune mechanism of ginkgo flavone glycosides regulating neurotrophin signaling pathway in CIRI rats

作　　者：赵坤[1] 张威[2] 车玉琴[1] ZHAO Kun;ZHANG Wei;CHE Yuqin(Department of Internal Medicine,Fourth Affiliated Hospital of China Medical University,Shenyang 110032,China;Department of Acupuncture Department,Affiliated Hospital,Liaoning University of Traditional Chinese Medicine,Shenyang110033,China)

机构地区：[1]中国医科大学附属第四医院内科,沈阳110032 [2]辽宁中医药大学附属医院针灸科,沈阳110033

出　　处：《免疫学杂志》2022年第8期645-654,共10页Immunological Journal

基　　金：国家自然科学基金(81703993)。

摘　　要：目的借助网络药理学手段,预测银杏黄酮苷治疗缺血性中风的可能作用靶点,并进行GO分析和KEGG通路分析,选择富集显著性强、排名靠前的通路,通过动物实验的方式进行验证分析,阐述银杏黄酮苷通过调控脑缺血再灌注损伤(cerebral ischemia-reperfusion injury,CIRI)大鼠神经营养素信号通路发挥抗炎等脑保护作用的机制。方法选用SPF级SD大鼠75只,随机分为假手术组(15只)和造模组(60只)。然后采用线栓法复制CIRI模型并评价,再将造模组随机分为模型对照组、银杏黄酮苷组、阳性对照组,分别给予相应的干预因素进行干预,观察各组大鼠神经功能缺损评分;血清IL-1β、IL-6、TNF-α含量;缺血半暗带脑组织中NGF、BDNF及Pan-Trk、p-Trk、PI3K、Akt、p-Akt、IκB的表达水平。结果共获取227个银杏素可能作用的靶点,脑梗死的疾病靶点24450个;二者交集靶点81个。与假手术组比较,其余各组大鼠神经功能缺损评分、血清中IL-1β、IL-6、TNF-α含量及缺血半暗带脑组织中NF-κB、p-NF-κB的表达水平显著升高(P<0.01),而Pan-Trk、p-Trk、PI3K、Akt、p-Akt、IκB的表达水平显著降低(P<0.01);与模型对照组比较,2干预组大鼠神经功能缺损评分、血清中IL-1β、IL-6、TNF-α含量及缺血半暗带脑组织中NF-κB、p-NF-κB的表达水平显著降低(P<0.05),而Pan-Trk、p-Trk、PI3K、Akt、p-Akt、IκB的表达水平显著升高(P<0.01)。结论银杏黄酮苷的抗炎作用可能是通过活化神经营养素信号通路,进而激活PI3K/Akt信号通路,抑制NF-κB的表达和磷酸化水平而实现的。This study was prepared to predict and verify possible targets of ginkgo flavone glycosides in treating ischemic stroke by network pharmacology and animal experiments,and to elucidate the anti-inflammatory mechanism of ginkgo flavone glycosides regulating neurotrophin signaling pathway in cerebral ischemia-reperfusion injury(CIRI)rats.Network tools were used to predict and screen the possible targets.Total of 75 SPF SD rats were recruited and randomly divided into sham group,model group,total flavonol glycocides(TFG)group and positive control group.The neurological deficit scores of rats in all groups were observed;the content of IL-1β,IL-6 and TNF-αin serum and the expression of NGF,BDNF,Pan-Trk,p-Trk,PI3K,Akt,p-Akt and IκB in brain tissue of ischemic penumbra were detected.Network tools found 227 possible targets for TFG and 24450 disease targets for cerebral infarction,in which there are 81 intersection targets.Animal experiment showed that the neurological deficit score,the contents of IL-1β,IL-6 and TNF-αin serum,and the expression levels of NF-κB and p-NF-κB in the brain tissue of ischemic penumbra in model group were significantly increased(P<0.01),as compared with the sham group.Compared with the model group,the neurological deficit score,the contents of IL-1β,IL-6 and TNF-αin serum,and the expression levels of NF-κB and p-NF-κB in brain tissue of ischemic penumbra in the two intervention groups were significantly decreased(P<0.05),and the expression levels of Pan-Trk,p-Trk,PI3K,Akt,p-Akt and IκB were significantly increased(P<0.01).In summary,the anti-inflammatory effect of TFG may be achieved by activating the neurotrophic signaling pathway,thereby activating the PI3K/Akt signaling pathway,and inhibiting the expression and phosphorylation of NF-κB.

关 键 词：银杏黄酮苷 脑缺血再灌注 网络药理学 神经营养素信号通路 

分 类 号：R392.5[医药卫生—免疫学]