Effect of muscle regions massage of Zhuang medicine on de-ubiquitination modification of NLRP3 mediated by BRCC3 in neuropathic pain rats and its analgesic mechanism
Effect of muscle regions massage of Zhuang medicine on de-ubiquitination modification of NLRP3 mediated by BRCC3 in neuropathic pain rats and its analgesic mechanism
Objective It is to investigate the effect of muscle regions massage of Zhuang medicine on the de-ubiquitina-tion modification of Nod-like receptor protein 3(NLRP3)mediated by de-ubiquitinating enzyme BRCC3 in rats with neuro-pathic pain(NPP)and its molecular mechanism of analgesia.Methods Forty-five female SPF grade SD rats were randomly divided into 5 groups:model group,normal group,group of muscle regions massage of Zhuang medicine,sham massage group and sham operation group,with 9 rats in each group.The models of NPP were established by L5 spinal nerve ligation in the model group,group of muscle regions massage of Zhuang medicine and sham operation group.Beginning on the first postoperative day,the rats of the sham massage group were gently stroked on the bilateral hind limbs,and the rats of the group of muscle regions massage of Zhuang medicine were treated with a massage acupressure manipulation simulator to stimulate the corresponding body surface parts of the spinal nerve ligated segments and the innervation areas of the ligated nerves and with massage,continuously treated for 14 days,while the remaining three groups were given no intervention and were observed for 14 days.The mechanical pain threshold and heat pain threshold of rats in each group were measured be-fore operation and at 1,3,and 14 days after operation;at 14 days after operation,the expressions of BRCC3 and NLRP3 mRNA in the dorsal horn of the L4-6 spinal cord were detected by qPCR,and the serum level of interleukin-1β(IL-1β)was detected by ELISA.Results At 1 and 3 days after operation,the mechanical pain threshold and heat pain threshold of rats in each surgical group were significantly lower than those in the normal group(all P<0.05);at 14 days after opera-tion,the mechanical pain threshold and heat pain threshold of rats in the group of muscle regions massage of Zhuang medi-cine were significantly higher than those in the model group and sham massage group(all P<0.05).At14 days after op-eration,the relative expressions of BRCC3 and NLRP3 mRNA in dorsal horn of spinal cord and levels of IL-1β in serum of rats in the model group and sham massage group were significantly higher than those in the normal group(all P<0.05),and the relative expressions of BRCC3 and NLRP3 mRNA in dorsal horn of spinal cord and levels of IL-1β in serum of rats in the group of muscle regions massage of Zhuang medicine were significantly lower than those in the model group and sham massage group(all P<0.05).Conclusion Muscle regions massage of Zhuang medicine can reduce the pain sensitivity of rats with neuropathic pain,and its mechanism is related to the down-regulation of the expression of the de-ubiquitination en-zyme BRCC3 in the dorsal horn of spinal cord,so as to inhibit the de-ubiquitination modification of NLRP3,thus to reduce the activation of NLRP3 and block maturity and secretion of IL-1β to block its mediated immune inflammatory reaction.
关键词
壮医经筋推拿/神经病理性疼痛/泛素化/白细胞介素-1β/NLRP3
Key words
muscle regions massage of Zhuang medicine/neuropathic pain/ubiquitination/IL-1β/NLRP3