[关键词]
[摘要]
基于NOD样受体热蛋白结构域相关蛋白3(NLRP3)信号通路探究天麻素注射液联合神经节苷脂辅助治疗脊髓损 伤(SCI)的可能机制。【方法】 将108例SCI患者随机分为观察组和对照组,每组各54例。2组患者均给予常规康复训练,在此 基础上,对照组给予神经节苷脂治疗,观察组给予天麻素注射液联合神经节苷脂治疗。30 d为1个疗程,连续治疗2个疗程。 比较2组患者的肌力恢复正常时间、可下地行走时间和留院观察时间,观察2组患者治疗前后美国脊柱损伤协会(ASIA)评分 及血清脑源性神经生长因子(BDNF)、中枢神经特异性蛋白(S-100β)、白细胞介素(IL)-1β、IL-18及NLRP3、半胱氨酸蛋白 酶1(Caspase-1)、凋亡相关斑点样蛋白(ACS)水平的变化情况,并评价2组患者的临床疗效及安全性。【结果】(1)治疗2个疗 程后,观察组的总有效率为 83.33%(45/54),对照组为 66.67%(36/54),组间比较(χ2检验),观察组的疗效明显优于对照组 (P<0.05)。(2)治疗后,观察组的肌力恢复正常时间、可下地行走时间及留院观察时间均较对照组明显缩短(P<0.01)。 (3)治疗 1 个和2个疗程后,2组患者ASIA的痛觉、运动、触觉评分均较治疗前明显升高(P<0.05),且治疗2个疗程后又较 治疗 1个疗程后升高(P<0.05);组间比较,观察组在治疗 1个和 2个疗程后对 ASIA的痛觉、运动、触觉评分的升高幅度均 明显优于对照组(P<0.05)。(4)治疗1个和2个疗程后,2组患者的血清BDNF水平均较治疗前升高(P<0.05),NLRP3、ACS、 Caspase-1蛋白和血清IL-1β、IL-18、S-100β水平均较治疗前下降(P<0.05),且治疗2个疗程后血清BDNF水平又均较治疗 1 个疗程后升高(P<0.05),NLRP3、ACS、Caspase-1 蛋白和血清 IL-1β、IL-18、S-100β 水平又均较治疗 1 个疗程后下降 (P<0.05);组间比较,观察组在治疗1个和2个疗程后对血清BDNF水平的升高幅度及对NLRP3、ACS、Caspase-1蛋白和血 清IL-1β、IL-18、S-100β水平的下降幅度均明显优于对照组(P<0.05)。(5)治疗过程中,2组患者均未出现药物相关不良反 应。【结论】 天麻素注射液联合神经节苷脂治疗 SCI患者疗效确切,可通过调控炎症小体 NLRP3信号通路,减轻神经炎症反 应,促进神经功能恢复,其疗效优于单纯神经节苷脂治疗。
[Key word]
[Abstract]
To explore the possible therapeutic mechanism of Gastrodin Injection combined with ganglioside in the adjuvant treatment of spinal cord injury (SCI) based on NOD-like receptor thermal protein domain associated protein 3(NLRP3) signaling pathway. Methods A total of 108 patients with SCI were randomly divided into an observation group and a control group,with 54 cases in each group. Both groups were given routine rehabilitation training. Additionally,the control group was treated with intravenous drip of ganglioside,and the observation group was treated with intravenous drip of Gastrodin Injection combined with ganglioside. A course of treatment covered 30 days and the two groups were treated for 2 continuous courses. The time for the recovery of muscle strength,time to leave a sickbed for walking and time to stay in hospital for observation were compared between the two groups. The American Spinal Injury Association(ASIA) score and the serum levels of brainderived neurotrophic factor (BDNF),central nervous specific protein(S-100β),interleukin (IL) -1β,IL-18, NLRP3, cystein-containing aspartate specific protease 1(Caspase-1) and apoptosis-associated speck-like protein containing a CARD (ASC) in the two groups were observed before and after treatment. After treatment,the clinical efficacy and safety of the two groups were evaluated. Results (1)After two courses of treatment,the total effective rate of the observation group was 83.33%(45/54),and that of the control group was 66.67%(36/54). The intergroup comparison (tested by chi-square test) showed that the curative effect of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the time for the recovery of muscle strength,time to leave a sickbed for walking and time to stay in hospital for observation in the observation group were significantly shorter than those in the control group(P<0.01).(3) After one and 2 courses of treatment,the ASIA scores of pain sense,motor sense and tactile sensation in the two groups were significantly higher than those before treatment (P<0.05),and the scores after 2 courses of treatment were higher than those after one course of treatment (P<0.05). The intergroup comparison showed that the increase of ASIA scores of pain sense,motor sense and tactile sensation in the observation group after one and 2 courses of treatment was significantly superior to that in the control group (P<0.05).(4) After one and 2 courses of treatment,the serum BDNF level in the two groups was higher than that before treatment (P<0.05) and the levels of NLRP3,ACS,Caspase-1 protein and serum IL-1β, IL-18 and S-100β were lower than those before treatment (P<0.05), and the changes in the levels of above indicators in the two groups after 2 courses of treatment were more obvious than those after one course of treatment (P<0.05). The intergroup comparison showed that the increase of serum BDNF level and the decrease of the levels of protein NLRP3, ACS, Caspase-1 and serum IL-1β, IL-18 and S-100β in the observation group were significantly superior to those in the control group (P<0.05).(5) During the treatment,no drug-related adverse reactions occurred in the two groups. Conclusion Gastrodin Injection combined with ganglioside exerts certain effect for the treatment of SCI patients. The combined therapy is effective on relieving the neuroinflammatory response and promoting the recovery of neurological function by regulating the NLRP3 inflammasomes,and its curative effect is superior to that of ganglioside alone.
[中图分类号]
R274.9
[基金项目]
云南省科技厅科技计划项目(编号:202201AY070001-085)