Study On The Mechanism Of IL-6/STAT3 In Regulating The Progression Of Chronic Non-bacterial Prostatitis By Inhibiting Autophagy

Background: Studies have shown that IL-6 plays a key role in the evolution of chronic non-bacterial prostatitis(CNP),but its specific mechanism is still unclear.However,the specific mechanism by which this cytokine regulates CNP is still unclear.At the same time,related literature reports that autophagy is involved in regulating the occurrence and evolution of inflammation.The mechanism may be related to IL-6/STAT3 signaling pathway and NLRP3 inflammasome.Materials and method: A total of thirty male Sprague-Dawley rats(8 weeks old),weighing 240-260 g,were purchased from the Experimental Animal Center of Anhui University(Hefei,China).Six SD male rats were randomly selected,and the rats prostate antigen extract and Freund’s adjuvant mixture were subcutaneously injected to construct rats model of chronic nonbacterial prostatitis(CNP),and then morphologically verified.After the model was successfully constructed,twenty-four male Sprague-Dawley rats were stochastically divided into 3 groups(8 in each group): CNP+IL-6(-)group,in which CNP model rats were intraperitoneally injected with IL-6 inhibitor 5mg/kg twice a week for 2 weeks;CNP group,in which CNP model rats were intraperitoneally injected with the same amount of normal saline;Control group,in which normal rats treatment the same as CNP group.Prostatic fluid was extracted from three groups of rats,and the IL-6 expression level was tested by ELISA method.After HE staining of prostate tissue to make pathology,the three groups of pathology were observed by morphology,and the expression of autophagy-related molecules,STAT3 pathway and NLRP3 inflammasome were detected by immunohistochemistry and western blotting.The three groups of rat prostate epithelial cells were extracted,and the autophagosome expression in the three groups of cells was observed by transmission electron microscope.There was no statistical difference in the weight of SD rats between the groups(P<0.05).Results: Histological analysis showed that compared with the control group,the expression level of IL-6 in the CNP group was significantly increased,and the inflammatory response in rats was obvious(P<0.05);Treatment with IL-6 inhibitors can significantly reduce the expression level of IL-6,and inflammatory response was also significantly reduced(P<0.05).Transmission electron microscopy(TEM)results showed that,compared with the control group,the expression level of autophagosomes with double membrane structure in the prostate tissue of the CNP group was significantly reduced,while the expression level of autophagosomes in the prostate tissue of rats in the IL-6 inhibitor group was increased significantly.In addition,the results of immunohistochemistry and western blot showed that compared with the control group,the expression level of autophagy-related markers in CNP group was reduced,and the expression level of p62 was increased;At the same time,the STAT3 pathway molecules and the expression level of NLRP3 inflammasome was significantly increased(P<0.05);After injecting with IL-6inhibitor,the autophagy-related markers expression level was significantly increased,and the expression of p62 was reduced(P<0.05);The expression levels of STAT3 pathway molecules and NLRP3 inflammasome also decreased significantly(P<0.05).Conclusion: This study shows that IL-6 can regulate CNP cell autophagy,and the STAT3 pathway and NLRP3 inflammatory complex are involved in IL-6 regulating chronic non-bacterial prostatitis(CNP)cell autophagy.Based on relevant literature reports,IL-6/STAT3 is involved in the regulation of autophagy in chronic non-bacterial prostatitis cells,and the NLRP3 inflammatory complex is also involved.These findings may provide a new theoretical basis for the pathogenesis of chronic non-bacterial prostatitis(CNP),as well as new ideas and targets for the treatment and prevention of chronic non-bacterial prostatitis(CNP).