Sodium Butyrate Alleviates Experimental Immune Prostatitis By Inhibiting Oxidative Stress And NLRP3 Inflammasome Activation Via The Nrf2/HO-1 Pathway

Objective: Patients with chronic prostatitis(chronicprostatitis,CP)account for about25% of the total number of urological outpatients in China.Due to the lack of awareness of the disease and the lack of satisfactory diagnosis and treatment,CP has perplexed many male patients for a long time.So far,the pathogenesis of CP is still unclear,and the disease is easy to relapse,thus increasing the psychological burden and economic pressure of patients.Through the in-depth exploration of experimental immune prostatitis(experimentalautoimmuneprostatitis,EAP),previous studies found that in addition to NLRP3 inflammatory bodies involved in the occurrence and development of CP,the imbalance of oxidative free radicals also plays an important role in CP.Sodium butyrate(Sodiumbutyrate,Na B),a kind of short-chain fatty acids(Shortchainfattyacids,SCFAs),participates in the regulation of oxidative stress and is a key metabolite affecting the regulation of inflammation.In this paper,we explored the therapeutic effect of sodium butyrate on experimental immune prostatitis model rats and explored its potential regulatory mechanism.Methods: The prostate of male adult SD(Sprague-Dawley)rats was used to prepare prostate antigen(PAg)and the model mice were constructed by autoimmune system.The animal experiment was carried out in two batches,and the full-week-old NOD mice were randomly divided into five groups.1.Rats with experimental autoimmune prostatitis were successfully established by immune modeling at 0 and 28 days,and sodium butyrate was supplemented according to dose.42 days after immunization,all groups of EAP mice were evaluated for behavioral pain before being killed,and the changes of prostate and serum related indexes were detected by tissue staining.2.WB and IHC were used to evaluate the changes of NLRP3 inflammatory bodies among different groups,and their correlation was analyzed.3.The pathways and factors related to oxidative stress were detected and evaluated by kit.Oxidative stress factor inhibitor was selected for verification.Finally,the specific regulation ways of the therapeutic effect of sodium butyrate are summarized,and the potential drug treatment targets are explored.Results: Sodium butyrate treatment alleviated the degree of prostatitis and pelvic pain in EAP mice,and significantly reduced the expression of inflammatory factors in prostate tissue.The initiation pathway of NLRP3 inflammatory bodies was inhibited by sodium butyrate.Sodium butyrate reduced oxidative stress and activated Nrf2/HO-1pathway in EAP mice.Nrf2/HO-1 pathway inhibitor can inhibit oxidative stress mediated by sodium butyrate.The inhibitory effect of sodium butyrate on the activation of inflammatory bodies can be blocked by Nrf2/HO-1 pathway.Therefore,blocking Nrf2/HO-1 signal pathway can block the anti-inflammatory effect of sodium butyrate in EAP.Conclusions: Sodium butyrate has significant anti-inflammatory effect on EAP.Sodium butyrate can improve the degree of prostatitis and relieve pain in the pelvic region of EAP mice.The activation of NLRP3 inflammatory bodies and the imbalance of free radicals in EAP mice were improved after treatment with sodium butyrate.Sodium butyrate inhibition of Nrf2/HO-1 pathway can not only inhibit oxidative stress in EAP mice,but also regulate the activation of NLRP3 inflammatory bodies,thus further reducing prostate inflammation.