目的 探討布托啡諾對(duì)脊髓損傷大鼠神經(jīng)細(xì)胞炎癥的影響及其機(jī)制。方法 復(fù)制脊髓損傷大鼠模型，將大鼠分為假手術(shù)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(duì)大鼠進(jìn)行運(yùn)動(dòng)功能評(píng)分，蘇木精–伊紅（HE）染色檢測(cè)脊髓組織病理變化，TUNEL染色檢測(cè)細(xì)胞凋亡，ELISA檢測(cè)脊髓組織腫瘤壞死因子-α（TNF-α）、白細(xì)胞介素（IL）-1β、IL-18水平，免疫熒光染色檢測(cè)小膠質(zhì)細(xì)胞，Western blotting檢測(cè)脊髓組織環(huán)磷酸鳥(niǎo)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(dá)。結(jié)果 與模型組比較，布托啡諾組脊髓組織損傷減輕，炎癥細(xì)胞減少，壞死細(xì)胞減少，Basso-Beattie-Bresnahan（BBB）評(píng)分顯著升高，脊髓組織細(xì)胞凋亡率、小膠質(zhì)細(xì)胞及TNF-α、IL-1β、IL-18水平，cGAS、STING、NLRP3、Caspase-1、IL-1β蛋白表達(dá)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(xì)胞排列較為松散，炎性細(xì)胞增多，BBB評(píng)分顯著降低，脊髓組織細(xì)胞凋亡率、小膠質(zhì)細(xì)胞及TNF-α、IL-1β、IL-18水平，cGAS、STING、NLRP3、Caspase-1、IL-1β蛋白表達(dá)水平顯著升高（P＜0.05）。結(jié)論 布托啡諾通過(guò)抑制cGAS/STING信號(hào)通路激活，抑制小膠質(zhì)細(xì)胞激活及炎癥反應(yīng)，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(huì)臨床專項(xiàng)研究基金（CXPJJH12000005-07-102）