参附注射液通过NgR1/Lingo-1/p75NTR复合物及RhoA/ROCKⅡ信号通路减轻心肺复苏脑损伤机制的研究  

Mechanism of Shenfu Injection Alleviating Cerebral Injury After Cardiopulmonary Resuscitation via NgR1/Lingo-1/p75NTR Complex and RhoA/ROCKⅡSignaling Pathway

作　　者：肖佳佳 邓海霞[2] 吴鑫宇 Xiao Jiajia;Deng Haixia;Wu Xinyu(Guangxi University of Chinese Medicine,Guangxi,Nanning 530022,China)

机构地区：[1]广西中医药大学,广西南宁530022 [2]广西中医药大学第一附属医院,广西南宁530022

出　　处：《中国中医急症》2025年第1期33-36,50,共5页Journal of Emergency in Traditional Chinese Medicine

基　　金：广西自然科学基金面上项目(2022GXNSFAA035450);广西中医药大学引进博士科研启动基金项目(2023BS031)。

摘　　要：目的观察参附注射液对心脏骤停后脑缺血再灌注损伤大鼠的神经保护作用,研究其是否通过调控NgR1/RhoA/ROCKⅡ信号通路及其上游因子Nogo受体相互作用蛋白1(Lingo-1)和p75神经营养因子受体(p75NTR),减轻脑损伤并促进神经轴突再生。方法制备心脏骤停/心肺复苏大鼠模型,将大鼠分为模型组、参附组、拮抗剂组及参拮组。通过ELISA检测各组脑组织中NgR1、p75NTR、Lingo-1、RhoA和RockⅡ的表达水平,并通过HE染色观察脑组织损伤情况。结果ELISA结果显示,心脏骤停后大鼠脑皮层中,模型组的各指标表达在特定时间点显著升高,尤其在3 d时NgR1、p75NTR、RhoA和ROCKⅡ达到峰值,显著高于空白组(P<0.01);参附组、拮抗剂组及参拮组的各指标表达水平均显著低于模型组(P<0.01),其中参拮组在所有时间点均表现出较低的NgR1、p75NTR、Lingo-1、RhoA及ROCKⅡ水平,尤其在3 d和7 d的ROCKⅡ和RhoA表达方面,显著低于模型组(P<0.01),RhoA在7 d时显著低于空白组(P<0.01)。HE染色结果表明,参附组和参拮组在各时间点的脑组织结构恢复效果优于模型组,细胞排列改善,水肿减轻。结论参附注射液通过调控NgR1/RhoA/ROCKⅡ信号通路及其上游因子,减轻了心脏骤停后脑缺血再灌注损伤,促进了神经轴突再生与功能恢复。Objective:To investigate the neuroprotective effects of Shenfu Injection(SFI)on cerebral ischemia-reperfusion injury in rats after cardiac arrest,with a focus on whether it alleviates brain injury and promotes axonal regeneration by regulating the NgR1/RhoA/ROCKⅡsignaling pathway and its upstream factors,including Nogo receptor interacting protein 1(Lingo-1)and p75 neurotrophin receptor(p75NTR).Methods:Using a cardiac arrest/cardiopulmonary resuscitation(CA/CPR)rat model,the rats were divided into a model group,a Shenfu group,an antagonist group,and a Shenfu Injection+antagonist group.The expression levels of NgR1,p75NTR,Lingo-1,RhoA,and RockⅡin brain tissues of each group were detected by ELISA,and the extent of brain tissue damage was observed by HE staining.Results:The ELISA results showed that in the cerebral cortex of rats after cardiac arrest,the expression of various indicators in the model group significantly increased at specific time points,with NgR1,p75NTR,RhoA,and ROCKⅡreaching peak levels at 3 days,significantly higher than those in the sham group(P<0.01).The expression levels of these indicators in the Shenfu,antagonist,and Shenfu+antagonist groups were significantly lower than those in the model group(P<0.01).Among them,the Shenfu+antagonist group exhibited the lowest levels of NgR1,p75NTR,Lingo-1,RhoA,and ROCKⅡat all time points,especially in the expression of ROCKⅡand RhoA at 3 and 7 days,which were significantly lower compared to the model group(P<0.01),the expression of RhoA was significantly lower than that in the blank group at 7 days(P<0.01).HE staining results indicated that the Shenfu and Shenfu+antagonist groups showed better structural recovery of brain tissue at each time point compared to the model group,with improved cell arrangement and reduced edema.Conclusion:Shenfu Injection alleviated ischemia-reperfusion injury following cardiac arrest by regulating the NgR1/RhoA/ROCKⅡsignaling pathway and its upstream factors,promoting axonal regeneration and functional recovery.

关 键 词：心肺复苏 脑损伤 参附注射液 NgR1/p75NTR/Lingo-1复合物 RhoA/RockⅡ信号通路 神经轴突再生 

分 类 号：R285.5[医药卫生—中药学]