早期使用丙戊酸钠对创伤性脑损伤后神经炎症影响的探索性研究

A pilot study on the effects of early use of valproate sodium on neuroinflammation after traumatic brain injury

摘要:

目的 研究早期使用丙戊酸钠对创伤性脑损伤（traumatic brain injury，TBI）后神经炎症的影响。方法 前瞻性选取2021年8月—2022年8月在徐州医科大学附属徐州儿童医院接受诊治或体检的45例儿童为研究对象，其中包括15例健康体检儿童为健康对照组，30例TBI患儿采用随机数字表法分为丙戊酸钠组和常规组，每组15例。丙戊酸钠组在常规治疗基础上加丙戊酸钠，常规组在常规治疗基础上加等量5%葡萄糖溶液。检测健康对照组体检当天，TBI患儿入院第1天、第3天、第5天血清核苷酸结合寡聚化结构域样受体蛋白3（nucleotide-binding oligomerization domain-like receptor protein 3，NLRP3）、高迁移率族蛋白B1（high mobility group box protein 1，HMGB1）、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）及白细胞介素-1β（interleukin-1β，IL-1β）浓度。评估出院2个月后TBI患儿格拉斯哥预后延伸评分。结果 TBI患儿第1天血清NLRP3、HMGB1、TNF-α和IL-1β浓度均显著高于健康对照组（P<0.017）；TBI患儿第5天NLRP3浓度高于第1、3天（P<0.017），第3、5天丙戊酸钠组NLRP3浓度低于常规组（P<0.05）；常规组第1、3、5天HMGB1浓度差异无统计学意义（P>0.017），丙戊酸钠组第5天HMGB1浓度低于第1、3天（P<0.017），第5天丙戊酸钠组HMGB1浓度低于常规组（P<0.05）；TBI患儿第1天TNF-α浓度低于第3、5天（P<0.017），第3、5天丙戊酸钠组TNF-α浓度低于常规组（P<0.05）；TBI患儿第3天IL-1β浓度高于第1、5天（P<0.017），第3、5天丙戊酸钠组IL-1β浓度低于常规组（P<0.05）；丙戊酸钠组出院2个月后格拉斯哥预后延伸评分高于常规组（P<0.05）。结论 早期使用丙戊酸钠可以减少TBI患儿神经炎症因子的释放，改善患儿预后。

Abstract:

Objective To study the effect of early use of sodium valproate on neuroinflammation after traumatic brain injury (TBI).Methods A total of 45 children who visited in Xuzhou Children's Hospital Affiliated to Xuzhou Medical University from August 2021 to August 2022 were enrolled in this prospective study, among whom 15 healthy children served as the healthy control group, and 30 children with TBI were divided into a sodium valproate treatment group and a conventional treatment group using a random number table (n=15 each). The children in the sodium valproate treatment group were given sodium valproate in addition to conventional treatment, and those in the conventional group were given an equal volume of 5% glucose solution in addition to conventional treatment. The serum concentrations of nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3), high-mobility group box 1 (HMGB1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were measured in the healthy control group on the day of physical examination and in the children with TBI on days 1, 3, and 5 after admission. Glasgow Outcome Scale-Extended (GOS-E) score was evaluated for the children with TBI 2 months after discharge.Results Compared with the healthy control group, the children with TBI had significantly higher serum concentrations of NLRP3, HMGB1, TNF-α, and IL-1β on day 1 after admission (P<0.017). The concentration of NLRP3 on day 5 after admission was significantly higher than that on days 1 and 3 after admission in the children with TBI (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of NLRP3 than the conventional treatment group (P<0.05). For the conventional treatment group, there was no significant difference in the concentration of HMGB1 on days 1, 3, and 5 after admission (P>0.017), while for the sodium valproate treatment group, the concentration of HMGB1 on day 5 after admission was significantly lower than that on days 1 and 3 after admission (P<0.017). On day 5 after admission, the sodium valproate treatment group had a significantly lower concentration of HMGB1 than the conventional treatment group (P<0.05). For the children with TBI, the concentration of TNF-α on day 1 after admission was significantly lower than that on days 3 and 5 after admission (P<0.017). On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of TNF-α than the conventional treatment group (P<0.05). The concentration of IL-1β on day 3 after admission was significantly lower than that on days 1 and 5 after admission (P<0.017) in the children with TBI. On days 3 and 5 after admission, the sodium valproate treatment group had a significantly lower concentration of IL-1β than the conventional treatment group (P<0.05). The GOS-E score was significantly higher in the sodium valproate treatment group than that in the conventional treatment group 2 months after discharge (P<0.05).Conclusions Early use of sodium valproate can reduce the release of neuroinflammatory factors and improve the prognosis of children with TBI.