目的 探讨布托啡诺对脊髓损伤大鼠神经细胞炎症的影响及其机制。方法 复制脊髓损伤大鼠模型，将大鼠分为假手术组、模型组、布托啡诺（100 μg/kg）组、布托啡诺＋2',3'-cGAMP（100 μg/kg布托啡诺＋500 μg/kg 2',3'-cGAMP）组，对大鼠进行运动功能评分，苏木精–伊红（HE）染色检测脊髓组织病理变化，TUNEL染色检测细胞凋亡，ELISA检测脊髓组织肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-18水平，免疫荧光染色检测小胶质细胞，Western blotting检测脊髓组织环磷酸鸟苷-磷酸腺苷酸合成酶（cGAS）、干扰素基因刺激因子（STING）、Nod样受体蛋白3（NLRP3）、半胱氨酸天冬氨酸蛋白水解酶-1（Caspase-1）、IL-1β蛋白表达。结果 与模型组比较，布托啡诺组脊髓组织损伤减轻，炎症细胞减少，坏死细胞减少，Basso-Beattie-Bresnahan（BBB）评分显著升高，脊髓组织细胞凋亡率、小胶质细胞及TNF-α、IL-1β、IL-18水平，cGAS、STING、NLRP3、Caspase-1、IL-1β蛋白表达水平显著降低（P＜0.05）；与布托啡诺组比较，布托啡诺＋2',3'-cGAMP组脊髓组织损伤加重，细胞排列较为松散，炎性细胞增多，BBB评分显著降低，脊髓组织细胞凋亡率、小胶质细胞及TNF-α、IL-1β、IL-18水平，cGAS、STING、NLRP3、Caspase-1、IL-1β蛋白表达水平显著升高（P＜0.05）。结论 布托啡诺通过抑制cGAS/STING信号通路激活，抑制小胶质细胞激活及炎症反应，改善大鼠脊髓损伤。

Objective To investigate the impact of butorphanol on nerve cell inflammation in rats with spinal cord injury and its mechanism. Methods Spinal cord injury rat models were duplicated and grouped into sham operation group, model group, butorphanol (100 μg/kg) group, and butorphanol + 2',3'-cGAMP (100 μg/kg butorphanol + 500 μg/kg 2',3'-cGAMP) group, the rats were scored for motor function, HE staining was applied to detect the pathological changes of spinal cord tissue, TUNEL staining was applied to detect apoptosis, the levels of TNF-α, IL-1β, and IL-18 in spinal cord tissue were detected by ELISA, immunofluorescence staining was applied to detect microglia, Western blotting was applied to detect the expression of cGAS, STING, NLRP3, Caspase-1, and IL-1β proteins in spinal cord tissue. Results Compared with model group, the injury of spinal cord tissue, inflammatory cells and necrotic cells were reduced in butorphanol group, BBB score was obviously higher, the apoptosis rate of spinal cord tissue, the levels of microglia and TNF-α, IL-1β, IL-18, and the protein expression of cGAS, STING, NLRP3, Caspase-1, and IL-1β were obviously decreased (P < 0.05). Compared with butorphanol group, the spinal cord tissue injury in butorphanol + 2',3'-cGAMP group was aggravated, the cell arrangement was loose, and inflammatory cells were increased, the BBB score was obviously lower, the apoptosis rate of spinal cord tissue, the levels of microglia and TNF-α, IL-1β, IL-18, and the protein expression of cGAS, STING, NLRP3, Caspase-1, and IL-1β were obviously higher (P < 0.05). Conclusion Butorphanol can improve spinal cord injury in rats by inhibiting the activation of cGAS/STING signal pathway and inhibiting the activation of microglia and inflammatory reaction.

R965；R971

湖北陈孝平科技发展基金会临床专项研究基金（CXPJJH12000005-07-102）