Toll样受体4拮抗剂对兔心脏停搏后脑损伤的影响  

Effect of TLR4 antagonist on brain injury in rabbits after cardiac arrest

作　　者：成静 陈芳 邱丽 王静 何意 杨虹 CHENG Jing;CHEN Fang;QIU Li;WANG Jing;HE Yi;YANG Hong(Department of Emergency Medicine,Wuhan Fourth Hospital,Wuhan,Hubei 430030,China)

机构地区：[1]武汉市第四医院急诊医学科,武汉430030

出　　处：《重庆医学》2025年第4期813-817,823,共6页Chongqing Medical Journal

基　　金：湖北省武汉市卫生健康委员会医学科研项目(WX21B07,WX20C20)。

摘　　要：目的建立兔心脏停搏(CA)模型后,观察Toll样受体4(TLR4)拮抗剂对兔心肺复苏后脑损伤的影响。方法选取72只体重2.8~3.3 kg的洁净级健康家兔,将72只家兔分为假手术组(Sham组)、CA组和TLR4拮抗剂组,排除心肺复苏失败、死亡、状态欠佳的家兔,最终每组20只纳入研究。Sham组仅进行动、静脉穿刺和气管插管,无致颤、CA及心肺复苏过程;余下2组均建立心肺复苏模型。TLR4拮抗剂组在ROSC后即刻、24 h、48 h给予TLR4拮抗剂(TAK-242溶液,3 mg·kg^(-1)·d^(-1)),CA组与相同时间点给予等量0.9%氯化钠溶液;Sham组在手术操作后即刻、24 h、48 h参考TLR4拮抗剂组给予等量0.9%氯化钠溶液。CA组和TLR4拮抗剂组分别于CA前及ROSC后12、24、72 h等时间点检测神经功能缺损评分(NDS)、神经元特异性烯醇化酶(NSE)水平,并于相同时间点检测Sham组上述指标;CA组和TLR4拮抗剂组于ROSC后72 h检测脑海马体组织中肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-1β表达水平和TLR4、核因子-κB(NF-κB)p65 mRNA表达水平,于相同时间点检测Sham组上述指标。结果CA组、TLR4拮抗剂组在ROSC后12、24、72 h的NDS均低于同期Sham组和同组CA前,差异有统计学意义(P<0.05);TLR4拮抗剂组ROSC后各时间点的NDS均高于CA组,差异有统计学意义(P<0.05)。CA组、TLR4拮抗剂组ROSC后12、24、72 h血清NSE水平均高于同期Sham组和同组CA前,差异有统计学意义(P<0.05);TLR4拮抗剂组ROSC后各时间点的血清NSE水平均低于CA组,差异有统计学意义(P<0.05)。ROSC后72 h,CA组、TLR4拮抗剂组TNF-α、IL-1β表达水平均高于Sham组,差异有统计学意义(P<0.05);TLR4拮抗剂组TNF-α、IL-1β表达水平低于CA组,差异有统计学意义(P<0.05)。与Sham组比较,ROSC后72 h CA组、TLR4拮抗剂组脑组织中TLR4、NF-κB p65 mRNA水平明显上升,差异有统计学意义(P<0.05);与CA组比较,TLR4拮抗剂组TLR4、NF-κB p65mRNA水平明显降低,差异有统计学意义(P<0.0Objective To establish a rabbit cardiac arrest(CA)model and observe the effect of a TLR4 antagonist on brain injury after cardiopulmonary resuscitation.Methods Seventy-two adult rabbits weighing 2.8-3.3 kg were divided into three groups:sham operation group(Sham group),CA group,and TLR4 antagonist group,with 24 rabbits in each group.The Sham group underwent only arterial/venous puncture and tracheal intubation without ventricular fibrillation,CA,or cardiopulmonary resuscitation.The CA group received equivalent volume of 0.9%sodium chloride solution at the same time points,while the TLR4 antagonist group received TAK-242 solution(3 mg·kg^(-1)·d^(-1))immediately,24 h and 48 h after ROSC.The Sham group received 0.9%sodium chloride solution(equivalent volume to the TLR4 antagonist group)immediately after the surgical procedure,and at 24 h and 48 h.Neurological deficit scores(NDS)and plasma neuron-specific enolase(NSE)levels were assessed before CA and at 12 h,24 h,and 72 h after ROSC.Tumor necrosis factor-α(TNF-α)and interleukin(IL)-1βlevels in hippocampal tissue were measured using ELISA.TLR4 and nuclear factor-κB(NF-κB)p65 mRNA expression levels were determined by RT-qPCR.Results At 12 h,24 h,and 72 h after ROSC,the neurological deficit scores(NDS)in both the CA group and TLR4 antagonist group were significantly lower than those in the Sham group and their respective pre-CA baselines(all P<0.05).However,the TLR4 antagonist group showed significantly higher NDS than the CA group at all post-ROSC time points(P<0.05).Serum neuron-specific enolase(NSE)levels in the CA group and TLR4 antagonist group were significantly elevated compared to the Sham group and their pre-CA baselines at 12 h,24 h,and 72 h after ROSC(P<0.05).Notably,the TLR4 antagonist group exhibited significantly lower serum NSE levels than the CA group at all time points(P<0.05).At 72 h post-ROSC,TNF-αand IL-1βexpression levels in both the CA group and TLR4 antagonist group were significantly higher than those in the Sham group(P<0.05),while the

关 键 词：心脏停搏 TOLL样受体4 脑损伤 TAK-242拮抗剂 

分 类 号：R743[医药卫生—神经病学与精神病学]