| Objective1) To evaluate the basic syndrome of TCM, pathogenesis features and evolution of chronic nonbacterial prostatitis;2) The characteristic cytokine screening of basic syndrome of TCM of chronic nonbacterial prostatitis with the syndrome of dampness-heat and stasis;3) To evaluate the effects of the characteristic cytokine in the pathogenesis of chronic nonbacterial prostatitis;4) To evaluate the molecular mechanism of Chinese herbal compound inhibiting inflammatory response on the basis of basic syndrome of TCM.Methods 1) The disease condition of 1083 chronic nonbacterial prostatitis patients from the first affiliated hospital of Hunan university of TCM were investigated. To study the distribution of syndrome and accompanying syndromes, the realation between TCM syndrome and other factors including types of diagnosis, disease courses and ages, the main symptoms and signs in TCM syndromes, and the bacis TCM syndrome of chronic prostatitis, the questionnaires for the distribution of syndrome in the chronic prostatitis patients were done by statistics analysis.2) The 38 patients of chronic nonbacterial prostatitis with basic TCM syndrome were randomly selected. Normal control group was selected from the population. The prostatic fluid were collected and then total protein were extracted. The expression of 40 main inflammatory cytokines in prostatic fluid were examed by antibody chip. The different proteins of inflammatory cytokines were screened.3) To investigated the regulation of inflammatory cytokines network in chronic nonbacterial prostatitis and determinate the characteristic cytokine, the different protein of inflammatory cytokines were verificated by western blot method.4) The experimental autoimmune prostatitis rat model was established by sc purified prostate protein twice with immune adjuvant. Compared with western medicine control of indomethacin, Chinese herbal compound on the basis of basic syndrome of chronic nonbacterial prostatitis was given to rats using gastric perfusion method. In order to study the molecular mechanism of the Chinese herbal compound inhibiting inflammation response, the pathology changes and expressions of mRNA and protein of characteristic cytokine in prostate of rat model were examined by methods of HE staining, immunohistochemistry and fluorescence quantitative RT-PCR respectively.Results1) The investigation of TCM syndrome in 1083 chronic prostatitis patients showed that two of four TCM syndromes, including damp-heat accumulation and qi stagnation and blood stasis, appear the high proportions of 91.51% and 84.30%. However, most of the TCM syndromes were accompanying syndromes, and the single syndrome only appears the low proportions of 3.88% and 2.22%. In all accompanying syndromes, two syndromes occupy more than proportion of 70%, the syndrome of damp-heat accumulation+ qi stagnation and blood stasis is the highest proportion of 56.79%, the next is the syndrome of damp-heat accumulation + qi stagnation and blood stasis+ insufficiency of kidney yang, which has the proportion of 14.59%. The single syndrome of damp-heat accumulation usually appears in patients of disease course below six months and few over six months. The accompanying syndromes of kidney deficiency have the more proportions with the longer disease course and over 30 years of age. The characteristic parterns of chronic prostatitis include the frequency of micturition, local fall-swell or pain in perineum, terminal dribbling. The majority (91.23%) of patients were diagnosised with the CAP/CPPS (Ⅲtype) and basic TCM syndrome of dampness-heat and stasis.2) The results of antibody chip assay for prostatic fluid of chronic nonbacterial prostatitis patients with syndrome of dampness-heat and stasis showed that the cytokines whose expressions enhanced higher than 1.5 times include Interleukin 1β(IL-1β), Interleukin 6 (IL-6), Interleukin 11 (IL-11), soluble tumor necrosis factor receptorⅡ(s TNF RⅡ), Platelet-derived growth factor BB (PDGF-BB), Monocyte chemoattractant protein 1 (MCP-1), Monocyte chemoattractant protein 2 (MCP-2). The cluster analysis results indicated that that the cytokines were divided into three major groups:the first group comprising the cytokines of PDGF-BB and MCP-1; the second group including IL-1β, IL-11, IL-6, MCP-2 and s TNF RⅡ; the third group comprising the remains cytokines. In all positive cytokines, IL-1β, IL-6, MCP-1, MCP-2, PDGF-BB are the pro-inflammatory cytokines and IL-11, s TNF RⅡare the anti-inflammatory cytokines. The expression of pro-inflammatory cytokines was much higher than anti-inflammatory cytokines.3) The expression of five cytokines including IL-1β, IL-6, MCP-1, PDGF-BB, s TNF RⅡenhanced in patients of chronic nonbacterial prostatitis. MCP-1, PDGF-BB, s TNF RⅡare the novel cytokines related to chronic prostatitis. The cytokines of TNF-a, IL-1β, IL-6 casue directly inflammatory response and the role of MCP-1 chemokine further increases the inflammatory reaction. The inflammation stimulates phagocytic cells or tissue cells to secret PDGF-BB which could promote glandular epithelial cell proliferation, anti-inflammatory cytokine s TNF RⅡcould inhibite biological effects of TNF-a.4) Eliminating dampness cooling and stasis-resolving decoction (SanCaoAnQian decoction) significantly reduces mRNA and protein expression levels of inflammatroy cytokines IL-1β, IL-6, inflammatory chemokines MCP-1 and inflammation-related growth factor PDGF-BB in rat model of chronic nonbacterial prostatitis, and effect of the high-dose group is higher than low-dose group (P<0.05). Indomethacin control group also significantly improves the expression levels of IL-1β, IL-6, but effects on MCP-land PDGF-BB are lower than the SanCaoAnQian decoction (P<0.01). The decoction may regulate and reduce the expression of TNF RⅡor s TNF RⅡby TNF-TNF R-s TNF R system regulation.Conclusions1) Dampness-heat, stasis are the basic TCM etiologies in chronic nonbacterial prostatitis and the critical factors on occurrence and development of chronic prostatitis. Kidney-deficiency which can be resulted from a long time illness or elderly natural recession, further leads to protracted illness as an important factor. 2) The basic TCM syndrome is dampness-heat and stasis in chronic nonbacterial prostatitis and appears in a majority of patients.3) Five inflammatory cytokines including IL-1β, IL-6, MCP-1, PDGF-BB, s TNF RⅡare the characteristic cytokines in chronic nonbacterial prostatitis with syndrome of dampness-heat and stasis. The immune and inflammatory response of chronic nonbacterial prostatitis are in a "weak balance" state of dominant proinflammatory factor.4) Eliminating dampness cooling and stasis-resolving is the basic treatment rule for chronic nonbacterial prostatitis. SanCaoAnQian decoction on the basis of treatment rule could inhibite inflammatory response and prevent epithelial cell proliferation and interstitial fibrosis in prostate by directly regulating TNF-α,IL-1β, IL-6, MCP-1, PDGF-BB and indirectly regulating TNF R, s TNFR. Molecular mechanisms involved in regulation of inflammatory cytokines network play an important role in the chronic nonbacterial prostatitis treatment of the decoction. |
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