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OA北大核心CSTPCD

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,50,100 μg/kg TP),and high-dose TP+stimulator of interferon gene(STING)activator group(TP-H+DMXAA group,100 μg/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 monophosphate-adenosine 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-1β and 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.