Study On The Mechanism Of Zishen Tongguan Method In The Treatment Of Type ? Prostatitis

Type ? prostatitis accounts for 90%of prostatitis,which has low cure rate,hi gh recurrence rate and long course of disease,seriously affects physical and m ental health,and brings heavy economic burden to patients.According to the 1 ower urinary tract symptoms and pelvic pain of type ? prostatitis,combined with the basic pathogenesis of kidney deficiency,dampness,heat and blood sta sis,the method of Zishen Tongguan is proposed to treat type ? prostatitis,an d received definite curative effect.Therefore,this study selected Zishen Tonggu an decoction as a starting point to explore the therapeutic mechanism of Zishe n Tongguan decoction in the treatment of type ? prostatitis in order to provid e experimental basis for clinical application of Zishen Tongguan decoction.Objective:To explore the mechanism of Zishen Tongguan decoction in the treatment of type ? prostatitis,and to explore the possible effect of Zishen Tongguan decoction in treating chronic prostatitis and slowing down its progression to benign prostatic hyperplasia and prostate cancer.Methods:The clinical study of traditional Chinese medicine for tonifying kidney,promoting blood circulation and promoting dampness in the treatment of chronic prostatitis from the date of establishment of PubMed,EMbase,The Cochrane Library,CNKI,CBM and WanFang Data database from to October 1,2020 was studied by systematic review.The literatures that met the requirements were included strictly according to the inclusion and exclusion criteria,and RevMan5.3 was used for Meta analysis to evaluate its effectiveness.The method of network pharmacology was used to predict the target of Zishen Tongguan decoction in the treatment of chronic prostatitis.The effective components of Zishen Tongguan decoction were screened by using drug target databases such as TCMSP and Swiss Target Prediction,and the component-target network of Zishen Tongguan decoction was constructed.CTD,PharmGKB,GAD and other disease target databases were used to construct the chronic prostatitis disease-target network.To build a common target protein interaction network by using String data platform,and analyse the GO functional enrichment of the network,biological process and signal pathway enrichment analysis of the selected core targets,the possible signal pathway of Zishen Tongguan decoction in the treatment of chronic prostatitis was obtained.Based on the action signal pathway revealed by network pharmacology,the basic experimental research on the intervention of Zishen Tongguan decoction on autoimmune model rats was carried out to verify the results of network pharmacology.The animal model was established by simultaneous injection of diphtheria tetanus vaccine,rat prostate protein purification solution and Freund's complete adjuvant suspension for 4 weeks.after the establishment of the model,the rats were randomly divided into low,middle and high dose Zishen Tongguan decoction group and western medicine group.The rats were given Zishen Tongguan decoction and tamoxin hydrochloride for 35 days.The histopathological changes of prostate in each group were observed by HE staining and Masson staining.The expression of IL-1 ?,IL-6,IL-10 and TNF-? in serum,and the expression of IL-1?,IL-6,IL-8,IL-10 and TNF-a in prostate tissue was detected by ELISA method.The expression of JAK2,p-JAK2,STAT3 and p-STAT3 protein was detected by Western Blot,and the expression of IL6 mRNA,JAK2 mRNA and STAT3 mRNA was detected by RT-PCR method.Results:1.According to the analysis of 25 literatures,the traditional Chinese medicine for tonifying kidney,promoting blood circulation and promoting dampness is effective in the treatment of chronic prostatitis,which is better than conventional western medicine.Based on the analysis of 25 articles with high frequency of use of traditional Chinese medicine,it is found that the drugs for nourishing kidney yin are more than those for warming kidney yang,reflecting the meaning of seeking yang in yin and less fire,and paying equal attention to dampness,clearing heat and activating blood circulation,reflecting the concept of simultaneous treatment of dampness,heat and blood stasis.2.Zishen Tongguan decoction has 168 components,which can act on 226target genes.There are 26414 disease targets in chronic prostatitis,of which 109 targets coincide with the action targets of Zishen Tongguan decoction.The(PPI)network of drug-disease interaction gene mapping protein interaction was analyzed,and the acting proteins of TOP5 were IL-6,EGFR,VEGFA,CCND1 and AR,respectively,suggesting that Zishen Tongguan decoction may interfere with prostatitis-cancer.3.The morphology of HE staining and' Masson staining confirmed that Zishen Tongguan decoction under the guidance of Zishen Tongguan method could reduce the infiltration of interstitial inflammatory cells and slow down the process of smooth muscle and collagen fibrosis.The expression of IL-1 ?,IL-6,IL-10 and TNF-? in serum decreased significantly in Zishen Tongguan decoction groups(P<0.01).Zishen Tongguan decoction can down-regulate the expression of IL-1 ?,IL-6,IL-8 and TNF-? in prostate tissue(P<0.01).Zishen Tongguan decoction in low dose group could down-regulate the expression of IL-10 in prostate tissue(P<0.01),while Zishen Tongguan decoction in high dose group could up-regulate the expression of IL-10 in prostate tissue(P<0.01).There was no significant difference in the expression of IL-10 in prostate tissue regulated by Zishen Tongguan decoction in middle dose group(P>0.05).The expression of p-JAK2 in prostate tissue of Zishen Tongguan decoction decreased significantly,but the expression of JAK2,STAT3 and p-STAT3 had no significant difference(P>0.05).The expressions of IL-6 mRNA,JAK2 mRNA and STAT3 mRNA of Zishen Tongguan decoction decreased significantly in all dose groups(P<0.01).Conclusion:Zishen Tongguan decoction can down regulate the expression of IL-1 ?,IL-6,IL-8 and TNF-? in rats,and regulate the expression of IL-10 bidirectionally.Zishen Tongguan decoction may improve the pathological changes of prostate tissue,reduce the infiltration of interstitial inflammatory cells,slow down the process of smooth muscle and collagen fibrosis,and reverse the progression of chronic prostatitis by reducing the expression of IL-6,JAK2 mRNA,STAT3 mRNA and p-JAK2.It is suggested that the effect of Zishen Tongguan decoction in the treatment of type III prostatitis may be achieved by regulating the expression of cytokines and IL-6/JAK2/STAT3 signal pathway.Zishen Tongguan decoction may slow down the occurrence and development of benign prostatic hyperplasia and prostate cancer while treating chronic prostatitis,but further research is needed.