【作者】 林兆丰；

【导师】 陈志强；

【作者基本信息】 广州中医药大学 ， 中医外科学， 2010， 博士

【摘要】 既往曾经认为慢性前列腺炎与前列腺癌无必定的内在联系,但近年来有关研究表明,慢性前列腺炎可能是前列腺癌的一个重要原因。已有研究提示免疫功能紊乱是前列腺癌发生发展的重要原因之一,同时也是前列腺炎和前列腺癌的共同特征。我院对前列腺癌的前期研究证实,通过调节免疫功能、扶正抑瘤的方法治疗晚期前列腺癌可以收到较好的疗效。同样,我院大量的实践与研究成果也表明,前列腺炎以湿热瘀阻的病机为主,以中医辨证为依据的利湿祛瘀法效果良好。前列腺炎好发于青壮年,且90%以上为非细菌性前列腺炎,免疫紊乱是一个重要因素,因此,我们设想,通过对前列腺炎患者有关瘤标及免疫相关指标的分析,中医药干预后的变化规律,以及建立前列腺炎患者的随访观察,或许能够对慢性前列腺炎与前列腺癌的内在联系,以及中医药对预防前列腺癌的作用得出有益的提示。目的观察Ⅲ型前列腺炎的免疫学变化,及其与前列腺特异抗原的关系,探讨中医利湿祛瘀对这些免疫指标的影响。以了解中医药辨证治疗对前列腺炎免疫学及其对前列腺特异抗原的影响,并作为对前列腺癌早期预防的初步探索。方法以广东省中医院泌尿外科门诊慢性Ⅲ型前列腺炎病人为样本52例,采用随机对照分组设置治疗组和对照组,分别通过治疗组根据辩证使用中医利湿祛瘀法(基本方加减治疗：川楝子10g元胡10g五灵脂10g蒲黄10g黄柏10g苍术10g牛膝10g苡米20g)；对照组则按照《中国泌尿外科疾病诊断治疗指南》推荐方案使用抗生素诺氟沙星治疗治疗,疗程2月。测定相关免疫指标,包括观察外周血T淋巴细胞亚群(CD3+T、CD4+T及CD8+T),血清PSA,前列腺按摩液EPS和TGF-β1的变化,对数据进行统计分析,对有关指标进行相关性分析,比较干预措施对免疫指标及PSA的影响。结果两组治疗前症状评分及生活质量评分之间均无统计学差别(P>0.05)。治疗2月后,治疗组各指标前后有显著差异(P<0.0001),对照组各指标前后数据除生活质量外都有统计学意义(P<0.05),生活质量前后无统计意义(P>0.05)。治疗后两组间均数有差别,其中两组间的疼痛症状、生活质量、整体总分差异具有显著意义(P<0.0001),而排尿症状两组间没有明显差异(P>0.05),症状总分两组间有统计学意义(P<0.05)。两组间各指标均差中排尿症状和生活质量有统计学意义(P<0.05)。两组间疼痛症状、症状评分、总体评分有显著性差异(P<0.0001)。两组治疗前总前列腺特异抗原(TPSA)水平没有统计学差异,治疗一月对照组TPSA水平有所下降,与治疗前有统计差异(P<0.05),治疗组TPSA水平有所下降,但无统计意义,两组间无明显差别。治疗二月数据显示治疗组TPSA水平有所下降,与治疗前有统计差异(P<0.05),对照组TPSA水平有所下降,与治疗前相比有统计学意义(P<0.05),两组间无显著差别。两组FPSA/TPSA在治疗前后,及组间均无统计学意义(P>0.05)。两组病例治疗前CD4+水平没有显著差异,治疗一月时治疗组CD4+水平有所上升,与治疗前无统计学意义(P>0.05),对照组CD4+水平有所上升,没有统计学意义(P>0.05)；两组间没有显著差别。治疗二月结果显示治疗组CD4+水平均有所上升,与治疗前有统计学意义(P<0.05),对照组CD4+水平有所上升,与治疗前相比无统计学意义(P<0.05)；两组间没有统计差别(P>0.05)。两组病例治疗前CD8+水平没有统计差异,治疗一月时治疗组CD8+水平有所上升,与治疗前无统计学意义(P>0.05),对照组CD8+水平有所上升,没有统计学意义(P>0.05)；两组间没有统计差别。治疗二月结果显示治疗组CD8+水平均有所上升,与治疗前有统计学意义(P>0.05),对照组CD8+水平有所上升,与治疗前相比无统计学意义(P>0.05)；两组间没有统计差别(P>0.05)。两组病例治疗前CD4+/CD8+水平没有显著差异,治疗一月时治疗组CD4+/CD8+水平有所上升,与治疗前无统计学意义(P>0.05),对照组CD4+/CD8+水平有所下降,没有统计学意义(P>0.05)；两组间没有统计差别。治疗二月结果显示治疗组CD4+/CD8+水平均有所上升,与治疗前没有统计学意义(P>0.05),对照组CD4+/CD8+水平有所上升,与治疗前相比无统计学意义(P<0.05)：两组间没有统计差别(P>0.05)。两组病例治疗前CD3+水平没有显著差异,治疗一月时治疗组CD3+水平有所下降,与治疗前无统计学意义(P>0.05),对照组CD3+水平有所下降,没有统计学意义(P>0.05)；两组间没有显著差别。治疗二月结果显示治疗组CD3+水平有所上升,与治疗前无统计学意义(P>0.05),对照组CD3+水平有所下降,与治疗前相比无统计学意义(P>0.05)；两组间无统计差别(P>0.05)。两组治疗前转化生长因子β1(TGF—β1)水平无显著差异,治疗一月时治疗组TGF-β1水平下降,与治疗前无统计意义(P>0.05),对照组TGF-β1水平有所下降,无统计学意义(P>0.05)；两组间没有显著差别。治疗二月结果显示治疗组TGF-β1水平有所下降,与治疗前有显著差异(P<0.0001),对照组TGF-β1水平下降,与治疗前相比有统计学意义(P<0.05)；两组间有统计学差异(P<0.05)。结论本研究在一定程度上证明Ⅲ型前列腺炎存在明显的免疫功能紊乱,表现在以整体的T淋巴亚群系列偏低表达为主,部分偏高表达的免疫功能紊乱,在这个层面上Ⅲ型前列腺炎与前列腺癌的免疫紊乱有一定的相似性,中医利湿祛瘀法为主的辨证治疗可以对这种免疫功能紊乱进行调节。该疗法对于细胞免疫的影响,首先明显地表现在对Th3细胞分泌的转化生长因子TGF-β1具有调节作用,其次这种中医疗法也可以在一定程度上改变CD4+CD8+CD3+以及CD4+/CD8+的低表达状态,提示该疗法可能有一定程度的抑制调节性T细胞的功能,同时描述性数据分析也显示出该疗法可能对细胞免疫具有调节作用。利湿祛瘀为主的中医疗法因此被认为具有调节Ⅲ型前列腺炎的免疫功能紊乱而使之趋于稳定平衡的作用。另外在对于PSA的影响上,我们的结论是在2个月的疗程后这种中医疗法与诺氟沙星没有明显差异。研究证实利湿祛瘀法对Ⅲ型前列腺炎在改善症状、提高生活质量方面具有明显的临床疗效；表明湿热淤阻在前列腺炎的发病过程中起重要作用,研究从一个侧面揭示了前列腺炎的主要病机,这对于前列腺炎的深化研究具有重要意义。更多还原

【Abstract】 Although the development of prostatic cancer is multi-factorial, accumulating evidences suggest that chronic prostatitis plays an important role in cancer development. Immune function disorder is considered as the common feature of prostatic cancer/carcinoma, as well as prosititis. My initial research confirmed that Traditional Chinese Medicine(TCM) is effective in treating advanced stage prostate cancer by regulating the immune function of patients and in curing prostatitis. So we assume that by analyzing the metastasis mark and immune-associated indexes of prostatic cancer patients, it is likely to get the curative regularity after TCM intervention, which may unveil the internal connections between chronic prostatitis and prostatic carcinoma, and may render a service to TCM preventive effect.Object iveTo investigate the influence of dialectic TCM therapy on treating prostatitis, and to make preliminary research on prevention of prostatic carcinoma by observing the immunological changes of Category III prostatitis and their relationship with prostatic specific antigen (PSA), and by evaluating the effectiveness of damp elimination and stasis removing on these immunological indexes.Materials and MethodsThere were 52 cases of patients with Category III prostatitis which were from Urology Clinic of Guangdong Provincial Chinese medicine Hospital. The subjects were randomized to treatment group and control group. Patients in treatment group were treated with TCM therapy to eliminating dampness and removing blood stasis(Basic recipe plus or minus:Toosendan 10g Yuanhu 10g Wulingzhi 10g Puhuang 10g HuangbailOg Cangshu 10g Niuxi 15g Coix bidentata 20g). While subjects in control group were treated with antibiotics Norfloxacin. The course of treatment was two months. During the treatment course, a series of immune parameters/immunolization indicators were measured and observed, including peripheral blood T lymphocyte subsets (CD3 +T, CD4+ T and CD8+ T), serum PSA, prostatic EPS:TGF-β1. Statistical analysis of the data were made to compare the influence of interventions on immune parameters/immunolization indicators.ResultsBefore treatment, the symptom score and quality of life score of two groups did not have statistical difference between (P>0.05). After 2 month treatment, in general, the most symptoms alleviated. Each index of the treatment group were significantly different compared with pre-treat level (P<0.0001). All the indicators of control group other than that of the quality of life have statistical significance (P<0.05). The quality of life had no statistically significant compared with pre-treat (P>0.05). After treatment, some differences between the average number of the two groups, of which the pain symptoms, quality of life, the overall total score difference was significant (P<0.0001), and the urinary symptoms between the two groups was no significant difference (P>0.05), total symptoms between the two groups was statistically significant (P<0.05). The average deviation between the two groups in urinary symptoms and quality of life have statistically significant (P<0.05), and the significant difference (P<0.0001) in the pain score, symptom score, overall score between two groups.Before treatment, the level of total prostatic specific antigen (T-PSA) of two groups did not have significant difference. After 1 month treatment, the level of PSA of control group declined significantly compared with pre-treat level (P<0.05); but without significance; the T-PSA level of treatment group declined without significance; and there was no marked difference between the two groups. At the end of the second treatment course, T-PSA level of both groups declined with marked significance (p<0.05); and there is no significant difference between the two groups. No statistical meaning existed in F/T before and after treatment.Before treatment, the CD4+/CD8+ level of two groups were not significantly different. At the end of the 1st month, CD4+/CD8+ level of the treatment group increased compared with pretherapy, with no significance (P>0.05); CD4+/CD8 +level of control group declined with no statistical significance (P>0.05); and there was no significant difference between the two groups. The 2nd month showed that the CD4+/CD8+ level of treatment group had risen, compared with pretherapy, which was significant (P<0.05). CD4+/CD8+ level of control group increased, compared with that pre-therapy condition but without significance (P>0.05); and no significant difference between the two groups (P>0.05).Before treatment, CD3+ levels of two groups had no significant difference. In the 1st month, CD3+ level of the treatment group increased, but was not significant (P>0.05), the CD3+, level of the control group decreased, but was not statistically significant(P>0.05); there was no significant difference between the two groups. In the 2nd month, it showed that the CD3+ level of treatment group increased compared with pretherapy, and it was significant (P<0.05); CD3+ level of the control group decreased, compared with that pre-therapy, which was not significant (P<0.05); and there was significant difference between groups (P<0.05).Before being treated, the transforming growth factorβ1 (TGF-β1) level of two groups was not significantly different. In the 1st month treatment, TGF-β1 level of the treatment group decreased, yet without significance (P> 0.05); that of control group declined was not statistically significant (P> 0.05); there was no significant difference between the two groups. In the 2nd month, it showed that the TGF-β1 level decreased in treatment group compared with pretherapy, without significance (P<0.05); the level of TGF-β1 of control group slightly increased compared with that pre-therapy conditions, which was not significant (P<0.05); and there was significant difference between the two groups (P<0.001).ConclusionsThe Research supported the point of view that obvious immune disorder exists in CategoryⅢprostatitis patients on some degree. Traditional Chinese medicine’s eliminating dampness and removing stasis treatment can regulate the immune function disorder. In regard to the impact of PSA, after 2 months of treatment, there’s no significant difference comparing Traditional Chinese Medicine therapy with the norfloxacin therapy. For the influence on cellular immunity, Traditional Chinese medicine can change, to some extent, the the low expression state of CD4+ CD8+ CD3+ and CD4+/CD8+, and regulate transforming growth factor TGF-β1 at the same time. Therefore, the TCM therapy on eliminating dampness and eliminating stasis was confirmed effective on regulating immune functional disorders of CategoryⅢprostatitis and on gearing immune function to normal level.更多还原