The Porostate Carcingenesis Study On C57BL/6 Prostatitis Mouse Modles

OBJECTIVES.Prostatitis refers to the inflammation in prostate glands.A variety of complex inflammatory,immune and neuroendocrine causes and inducements lead to the complicated prostate pathological changes.Prostatitis characterized by varied lower urinary tract symptoms included chronic pelvic pain,urethral irritation symptoms and abnormal urination and so on.Chronic prostatitis mainly involves chronic bacterial prostatitis(CBP,type II)and chronic pelvic pain syndrome(CPPS,type III).Prostate cancer is one of the most common cancers of the male reproductive system.There is increasing evidence that the occurrence and development of tumor is closely related to chronic disorders in vivo microenvironment,and inflammation is highly correlated with various cancers.And the occurrence and pathogenesis of prostate cancer are associated with inflammatory mediators.This study aimed to explored the relationship between prostatitis and prostate cancer by building C57BL/6 chronic bacterial prostatitis and chronic pelvic pain syndrome mouse models.And provided experimental basis to investigate the characteristics of prostatitis and the role of prostatitis in the occurrence and development of prostate cancer.METHODS.In this study,we set up two C57BL/6 mouse models ofprostatitis induced by prostate extract protein immunization(experimental autoimmune prostatitis,EAP group)or E.coli infection(E.coli group)respectively.90 male C57BL/6 mice were randomly divided into 3 groups included blank group,control group and model group.EAP group mice were injected subcutaneously in the abdominal flank with 200 μl of an emulsion consisting of equal amounts of water and complete Freund’s adjuvant(CFA,100μg prostate extract protein.CFA group mice were injected without prostate extract protein.E.coli group were anaesthetized and instilled with 200 μl of E.coli solution intraurethrally using sterile polyethylene tubing.PBS group were anaesthetized and instilled with sterile PBS,and na?ve mice were also included as controls.Histological evaluation of the inflammatory response was performed using Haematoxylin & Eosin(H&E)stain,Masson’s trichrome stain,CD45 immunohistochemical expression and C-reactive protein(CPR)serum level.The development of chronic pelvic pain was measured by Von Frey filaments.Histological estimation of the initiation of prostate cancer was evaluated using the Prostate Volume Index(PVI),serum level of IL-17 and TEM microstructure changes.Prostate apoptosis were determined by immunohistochemical expression of HSP60.The phenotype of proliferating prostate epithelial cells was determined using CK5 and CK8 immunofluorescence staining.We can observed the changes of prostate epithelial cells by immunofluorescence staining with CK5 and CK8.Using Image Pro Plus 6 software to calculate the average optical density of immunohistochemistry.GraphPad Prism 5 statistical software was used to performed Two-way ANOVE analysis and and Student t-test to determine significance between groups,the 0.05 level of confidence was accepted for statistical significance.RESULTS.From 1 to 6 months,when compared to control and na?vegroups,the EAP group and E.coli group showed higher expression of CD45(P<0.001),increased collagen deposition(P<0.05)and a reduction in the amount of smooth muscle(P<0.05).Serum levels of IL-17 increased significantly and pelvic pain thresholds decreased significantly.Additionally,CRP serum levels were significantly higher at 1 month,but decreased to close to control and na?ve group levels at 3 and 6 months.The immunofluorescence results showed high proliferation of basal and luminal cells in most prostate glandular tissue from 1to 6 months.However,at 6 months,regions of the prostate glandular tissue in the EAP and E.coli groups showed disappearance of basement membrane,and immunohistochemical CK5 expression confirmed the disappearance of basal cells,which indicated carcinogenesis in the EAP and E.coli groups.CONCLUSIONS.We successfully created chronic prostatitis mouse models featuring chronic bacterial prostatitis and chronic pelvic pain syndrome.Both the EAP and E.coli group demonstrated canceration in some local prostate tissue at 6 months.This study provides direct evidence that chronic inflammation could accelerate the initiation and progression of prostate cancer.