右美托咪定通过调控TLR4/My D88/NF-κB信号通路预防重型颅脑损伤患者PSH的疗效观察

Effect of dexmedetomidine on the prevention of PSH in patients with severe craniocerebral injury by regulating TLR4/My D88/NF-kappa B signaling pathway

目的探讨右美托咪定调控Toll样受体4(TLR4)/髓样分化因子(MyD)88/核转录因子(NF)-κB信号通路(TLR4/My D88/NF-κB)预防重型颅脑损伤患者阵发性交感神经过度兴奋(paroxysmal sympathetic hyperactivity,PSH)的临床疗效。方法选取本院2016年9月~2019年5月收治的100例重型颅脑损伤患者为研究对象,随机数字表法分为研究组和对照组各50例,研究组在麻醉诱导前给予1.0μg/kg负荷量的右美托咪定,后续以0.4μg·kg-1·h-1输注,对照组注射等量生理盐水。比较两组PSH发生率、临床症状、影像学表现、机械通气时间、气管插管/切开时长、ICU住院时间、总住院时长以及出院后3个月的GCS评分;同时检测两组治疗后外周血CD14+单核细胞中MyD88的荧光强度、TLR4、NF-κB表达水平,以及肿瘤坏死因子-α(TNF-α)表达水平。结果研究组7 d和3个月时PSH发生率显著低于对照组(P<0.05),且研究组总住院时长、ICU住院时长、术中气管切开比例以及机械通气时间均显著低于对照组,GCS评分高于对照组,差异具有统计学意义(P<0.05)。另外影像学结果显示两组患者的影像学病灶位置存在一定差异,对照组中患者病灶位于脑室系统及周围的比例高于研究组(P<0.05)。两组T1~T3时CD14+PBMC MyD88荧光强度、TLR4和NK-κB阳性表达率相比T0均显著增高(P<0.05),但研究组患者在T1~T3时MyD88荧光强度、TLR4和NK-κB阳性表达率相比对照组明显降低(P<0.05)。两组T1~T3时血清TNF-α表达水平相比T0均显著增高(P<0.05),但研究组T1~T3时血清TNF-α表达水平相比对照组明显降低(P<0.05)。结论右美托咪定可以通过抑制TLR4/My D88/NF-κB信号通路减少重型颅脑损伤患者机体氧化应激反应,从而有效降低PSH发生风险,改善患者预后。

Objective To investigate the clinical efficacy of dexmedetomidine in the regulation of TLR4/My D88/NF-κB in the prevention of paroxysmal sympathetic over-excitation(PSH)in patients with severe head injury.Methods A total of one hundred patients with severe head injury who were admitted to our hospital from September 2016 to May 2019 were enrolled.The randomized digital table method was divided into 50 cases in the study group and the control group.Patients in the study group were given dexmedetomidine at a dose of 1.0μg/kg before anesthesia induction,followed by infusion at 0.4μg/(kgh),and the control group was injected with the same amount of normal saline.The incidence of PSH,clinical symptoms,imaging findings,mechanical ventilation time,tracheal intubation/incision duration,ICU hospitalization time,total length of hospital stay,and GCS scores three months after discharge were compared between the two groups.At the same time,the fluorescence intensity,TLR4,NF-κB expression level and tumor necrosis factor-α(TNF-α)expression levels in peripheral blood CD14+monocytes of the two groups were detected.Results The incidence of PSH was significantly lower in the study group than in the control group at 7 and 3 months(P<0.05).The total length of hospital stay,duration of ICU hospitalization,intraoperative tracheotomy,and mechanical ventilation time were significantly lower in the study group than in the control group.And the GCS score was higher than the control group,and the difference was statistically significant(P<0.05).In addition,the imaging results showed that there were some differences in the location of imaging lesions between the two groups.The proportion of lesions in the ventricular system and surrounding areas was higher in the control group than in the study group(P<0.05).And the T14-T3 CD14+PBMC MyD88 fluorescence intensity,TLR4 and NK-κB positive expression rate were significantly higher than those of T0(P<0.05),but the MyD88 fluorescence intensity,TLR4 and NK-κB positive expression rate in the study group were significantly lower than those in the control group at T1-T3(P<0.05).The levels of serum TNF-αin T1-T3 groups were significantly higher than those in T0(P<0.05),but the levels of serum TNF-αin T1-T3 in the study group were significantly lower than those in the control group(P<0.05).ConclusionDexmedetomidine can reduce the oxidative stress response in patients with severe head injury by inhibiting TLR4/My D88/NF-κB signaling pathway,thus effectively reducing the risk of PSH and improving the prognosis of patients.