雷公藤甲素调节cGAS/STING信号通路对坐骨神经痛大鼠的改善作用及机制  

Improvement effect and mechanism of triptolide on sciatica rats by regulating cGAS/STING signaling pathway

作　　者：闫改霞 林淑霞 孟燕 张慧宇 景彦林 YAN Gaixia;LIN Shuxia;MENG Yan;ZHANG Huiyu;JING Yanlin(College of Traditional Chinese Medicine Health Service,Shanxi Datong University,Shanxi Datong 037009,China)

机构地区：[1]山西大同大学中医药健康服务学院,山西大同037009

出　　处：《中国药房》2024年第13期1594-1599,共6页China Pharmacy

基　　金：山西省基础研究计划(自由探索类)项目(No.20210302123478)。

摘　　要：目的 探究雷公藤甲素(TP)对坐骨神经痛大鼠的改善作用及机制。方法 制备坐骨神经痛大鼠模型,然后将大鼠随机分为模型组(生理盐水),吲哚美辛组(阳性对照,7.5 mg/kg),低、高剂量TP干预组(分别记为TP-L组、TP-H组,50、100μg/kg TP)和高剂量TP+干扰素基因刺激因子(STING)激活剂干预组(TP-H+DMXAA组,100μg/kg TP+25 mg/kg DMXAA),每组12只;另取12只不结扎的大鼠作为假手术组(生理盐水)。腹腔注射给药/生理盐水14 d后,检测大鼠机械刺激缩足反射阈值(PWT)、热刺激缩足反射潜伏期(PWL);观察大鼠坐骨神经病理学改变、坐骨神经元形态及小胶质细胞数;检测大鼠坐骨神经中白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平及环磷酸鸟苷-腺苷酸合成酶(cGAS)、STING mRNA及其蛋白表达。结果 与假手术组比较,Model组大鼠PWT、PWL均显著降低/缩短(P<0.05),尼氏体数量显著减少(P<0.05);小胶质细胞数、坐骨神经病理学评分,IL-1β、TNF-α水平,cGAS、STING mRNA及其蛋白表达水均显著增加/升高(P<0.05);坐骨神经损伤严重。与Model组比较,吲哚美辛组、TP-L组、TP-H组大鼠各指标变化与上述相反(P<0.05),坐骨神经损伤减轻。STING激活剂DMXAA减弱了TP对坐骨神经痛大鼠小胶质细胞活性和炎症反应的抑制作用(P<0.05)。结论 TP可能通过下调cGAS/STING信号通路,降低小胶质细胞活性和炎症反应,从而改善大鼠坐骨神经痛。OBJECTIVE To investigate the improvement effect and mechanism of triptolide(TP)on sciatica rats.METHODS Sciatica rat model was prepared and then randomly divided into model group(normal saline),indomethacin group(positive control,7.5 mg/kg),TP low-dose and high-dose groups(TP-L group and TP-H group,50,100μg/kg TP),and high-dose TP+stimulator of interferon gene(STING)activator group(TP-H+DMXAA group,100μg/kg TP+25 mg/kg DMXAA),with 12 rats in each group.Another 12 unligated rats were selected as sham operation group(normal saline).After 14 days of intraperitoneal administration,the paw mechanical withdrawal threshold(PWT)and paw withdrawal thermal latency(PWL)were detected;the pathological changes,morphology of sciatic nerve and the number of microglia in sciatic nerve were observed.The levels of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α),mRNA and protein expression levels of cyclic guanosine monophosphateadenosine monophosphate synthase(cGAS)and STING in sciatic nerve were detected.RESULTS Compared with sham operation group,PWT and PWL of rats in model group were obviously reduced and shortened,the number of Nissl bodies was obviously decreased,while the number of microglia,sciatic neuropathology score,the levels of IL-1βand TNF-α,mRNA and protein expressions of cGAS and STING were obviously increased(P<0.05),and sciatic nerve injury was serious.Compared with model group,the changes of various indexes in indomethacin group,TP-L group and TP-H group were opposite to the above(P<0.05),and sciatic nerve injury was reduced.STING activator DMXAA weakened the inhibitory effect of TP on the activity of microglia and inflammatory response in sciatica rats(P<0.05).CONCLUSIONS TP may reduce the activity of microglia and inflammatory response by down-regulating the cGAS/STING signaling pathway,thus alleviating sciatica in rats.

关 键 词：雷公藤甲素 坐骨神经痛 cGAS/STING信号通路 小胶质细胞 炎症反应 

分 类 号：R965[医药卫生—药理学]