Effect of electroacupuncture on brain-gut co-treatment in rats with cerebral ischemia based on TMAO-HMGB1/NLRP3 pathway

ObjectiveTo observe the effect of electroacupuncture （EA） on the trimethylamine-N-oxide （TMAO）-high mobility group box 1 protein （HMGB1）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway in cerebral ischemia （CI） rats， so as to explore its mechanism in brain-gut co-treatment.MethodsMale SD rats were randomly divided into sham operation， model and EA groups， with 15 rats in each group. The CI model was established by occlusion of the middle cerebral artery （MCAO）. EA was applied to “Baihui” （GV20）， “Tianshu” （ST25）， “Shangjuxu” （ST37）， and “Dazhui” （GV14） for 20 min， once every other day for 14 d. Neurological deficit was assessed using the Zea-Longa score. The cerebral infarction volume was detected by TTC staining， the pathological changes in the ischemic cerebral cortex and colon tissues were observed by HE staining. The contents of TMAO， HMGB1， NLRP3， interleukin （IL）-1β， zonula occludens-1 （ZO-1）， and Occludin in serum， colon， and ischemic cerebral cortex were detected by ELISA. The protein and mRNA expression levels and positive expression of HMGB1， NLRP3， IL-1β， ZO-1 and Occludin in colon tissue and ischemic cerebral cortex were detected by Western blot， real-time fluorescent quantitative PCR， and immunofluorescence staining， respectively.ResultsAfter modeling and compared with the sham operation group， the Zea-Longa score and the percentage of cerebral infarction volume， the contents of TMAO， HMGB1， NLRP3 and IL-1β in serum， colon and ischemic cerebral cortex， the expression levels and positive expressions of HMGB1， NLRP3， IL-1β protein and mRNA in colon and ischemic cerebral cortex were significantly increased （PPPConclusionEA mediating brain-gut co-treatment can reduce the content of intestinal flora metabolite TMAO， down-regulate the expressions of HMGB1/NLRP3 in intestinal tissue， and reduce peripheral inflammatory factors， thereby alleviating the inflammatory response in brain tissue of MCAO rats.