| Background:Chronic non-bacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disease of male reproductive system. The etiology and the pathogenesis of CP are not yet clear so far. Because of the high incidence of the disease, lack of typical symptoms, and difficulty to treat, CP seriously impairs the quality of life in patients. Recently studies have shown that CP is the result of a variety of factors. Autoimmune reactions play an important role in the pathogenesis which is mediated by inflammatory cytokines. Pain, voiding dysfunction and sexual dysfunction are three main manifestations of CP. Many investigations ascribed the voiding dysfunction to the functional obstruction at posterior urethra which evokes non-inhibitive contraction and eventually leads to unstable bladder. However, among some patients without functional urethral obstruction, symptoms and abnormal urodynamic findings are also present.Interstitial cells of Cajal (ICC) in the bladder act as pacemaker and have strong relationship with nerve terminal. The increase of ICC-like cells in the detrusor, which maybe lead to an enhanced spontaneous contraction of detrusor, and may be one of the important mechanisms of detrusor instability (DI). The abnormal function of bladder was the main reason for the voiding dysfunction. The question is:are there any relationship with the alteration of bladder ICC-like cells in the association between voiding dysfunction and CP? To the best of our knowledge, there were very few studies addressing this question.Sinomenine was widely used in clinical practice because of its effects of anti-inflammatory, immunosuppression and inhibitory action to gastro-intestinal smooth muscle. It was recognized that acupuncture on relative points had therapeutic effects on CP symptoms and bladder hyperactivity. As such, elucidation of the mechanism at myogenic level of detrusor of bladder will facilitate treatment of CP and the concomitant bladder dysfunction.Objective:To observe the alteration of bladder function and its ICC-like cells in SD rat model of experimental autoimmune prostatitis (EAP), and to investigate the effects of Sinomenine and acupuncture at Zhonglushu and Huiyang point on morphological peculiarities of experimental rats prostate tissue and the concomitant bladder dysfunction, and evaluated their efficacy.Method:The model of experimental autoimmune prostatitis (EAP) rat was made by DPT vaccine in peritoneal injection and rat prostatein purification of FCA emulsion multiple intra-dermal injections for 45 days. Cystometries were performed in conscious rats after suprapubic bladder puncture. The bladder capacity, pressure and postvoiding volume were measured and the incidence of detrusor instability was studied. Then prostate glands were obtained to investigate the histomorphological changes. Detrusor tissue pieces were obtained for detecting c-kit positive cells by immunofluorescent staining.Fifty SD rats were randomly divided into a control group, a model group, an acupuncture group and the groups of low, medium and high dose of Sinomenine. The low, medium and high dose group was given dose of 10, 20,30mg/kg, respectively, by intraperitoneal injection. The acupuncture group was electroacupunctured at Huiyang (BL 35) and Zhonglushu (BL 29) with output voltage of 4～6V, dense wave of 20 Hz and distant wave of 4 Hz. The above groups were subsequently treated for 14 days, qd. Finally, cystometries, histomorphological observation of prostate and detection of c-kit positive cells in bladder were performed. The bladder detursor tissues were harvested for a reverse transcription polymerase chain reaction (RT-PCR) exam of NGFmRNA.The contents of IL-1β, PGE2 and β-endorphin in prostate-homogenate were detected by enzyme linked immunosorbent assay.Results:The incidence of DI developed in model group was 70%. Bladder pressure and capacity decreased from (27.3±1.87) cmH2O and (0.57±0.06) mL in control rats to (22.8±2.03)cmH2O and (0.39±0.05)mL in model rats, respectively (P< 0.05). The postvoiding volume increased from (0.11±0.04)mL to (0.33±0.06)mL. The model group showed chronic inflammation in prostate glandular tissue. The above results indicated that the model was built successfully and was a candidate for further study on bladder dysfunction secondary to CP.Compared with control group, model group showed considerably increase in number of ICC-like cells and decrease of integral optical density value (IOD) in the detrusor. The ICC-like cells were arranged disordered, and the intercellular connection was scattered in model group.After acupuncture and administration of Sinomenine, DI ratio of model group, acupuncture group, Sinomenine high dose group, medium dose group and low dose group was 60%,10%,20%,40%, and 50%, respectively. Compared with that of the model group,the bladder capacity and maximum detrusor pressure increased,and the residual volume decreased significantly in the treatment group.In the high dose group of Sinomenine and acupuncture group, the epithelial tissues recover, the architecture of epithelial tissues were integrated, and the interstitial edemas disappeared. In the mid and low dose group, the damage of prostate gland tissues recovered slightly. According to classified statistical analysis, the differences among each group of the Sinomenine and the acupuncture group had statistical significance.Compared with the model group, the number of ICC-like cells (c-kit positive cells) decreased significantly and ICC-like cells were arranged more orderly in the Sinomenine and acupuncture groups. The expression levels of NGF in high dose and mid dose group of Sinomenine and in acupuncture group were significantly decreased compared with that in model group, the alteration of expression levels of NGF and ICC-like cells had positive correlationCompared with the model group, the level of PGE2 and IL-1βof prostate glandular tissues reduced in both Sinomenine and acupuncture groups, whereasβ-EP increased obviously.Conclusion:Using the way of autoimmune reaction to induce the CP animal model, the change in pathology of the animal's prostate tissue was most similar to that of patients, and pathogenesis is relatively consistent with patients. It was a satisfactory way to induce CP animal model.The CP animal model was present with bladder dysfunction of DI and alteration of ICC like cells in detrusor. The alteration of ICC-like cells in number and distribution was associated with the voiding dysfunction of CP rat model.Sinomenine and acupuncture at Zhonglushu and Huiyang point can remarkably lower down the levels of PGE2 and IL-1β, increase theβ-EP level in rats with nonbacterial chronic prostatitis, reduce or eliminat inflammation of rat prostate tissue, and improve its organizational structure damage. They had an anti-fibrosis effect and play an important role in protecting prostate issue.The results of this study were suggested that there would be interaction between ICC-like cells and NGF in detrusor, and the protective effect of Sinomenine and acupuncture on prostate tissue would influence the quantity and distribution of bladder ICC-like cells directly or by means of immunosuppression and regulation of neurotransmitters. |
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