目的 探討布托啡諾對脊髓損傷大鼠神經(jīng)細胞炎癥的影響及其機制。方法 復制脊髓損傷大鼠模型，將大鼠分為假手術組、模型組、布托啡諾（100 μg/kg）組、布托啡諾＋2',3'-cGAMP（100 μg/kg布托啡諾＋500 μg/kg 2',3'-cGAMP）組，對大鼠進行運動功能評分，蘇木精–伊紅（HE）染色檢測脊髓組織病理變化，TUNEL染色檢測細胞凋亡，ELISA檢測脊髓組織腫瘤壞死因子-α（TNF-α）、白細胞介素（IL）-1β、IL-18水平，免疫熒光染色檢測小膠質(zhì)細胞，Western blotting檢測脊髓組織環(huán)磷酸鳥苷-磷酸腺苷酸合成酶（cGAS）、干擾素基因刺激因子（STING）、Nod樣受體蛋白3（NLRP3）、半胱氨酸天冬氨酸蛋白水解酶-1（Caspase-1）、IL-1β蛋白表達。結果 與模型組比較，布托啡諾組脊髓組織損傷減輕，炎癥細胞減少，壞死細胞減少，Basso-Beattie-Bresnahan（BBB）評分顯著升高，脊髓組織細胞凋亡率、小膠質(zhì)細胞及TNF-α、IL-1β、IL-18水平，cGAS、STING、NLRP3、Caspase-1、IL-1β蛋白表達水平顯著降低（P＜0.05）；與布托啡諾組比較，布托啡諾＋2',3'-cGAMP組脊髓組織損傷加重，細胞排列較為松散，炎性細胞增多，BBB評分顯著降低，脊髓組織細胞凋亡率、小膠質(zhì)細胞及TNF-α、IL-1β、IL-18水平，cGAS、STING、NLRP3、Caspase-1、IL-1β蛋白表達水平顯著升高（P＜0.05）。結論 布托啡諾通過抑制cGAS/STING信號通路激活，抑制小膠質(zhì)細胞激活及炎癥反應，改善大鼠脊髓損傷。

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

湖北陳孝平科技發(fā)展基金會臨床專項研究基金（CXPJJH12000005-07-102）