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前癃通胶囊治疗良性前列腺增生症临床观察及对人前列腺组织Bcl-2、Bax表达的影响

Clinical Observation of Qian Long Tong Capsule on Treating Benign Prostate Hyperplasia and the Influence on the Expressions of Bax, Bcl-2 in Human Prostatic Tissue

【作者】 蔡蔚

【导师】 贺菊乔;

【作者基本信息】 湖南中医药大学 , 中医外科学, 2008, 博士

【摘要】 目的:1.观察前癃通胶囊治疗BPH的临床疗效。2.检测前癃通对前列腺组织细胞凋亡指数及细胞周期的影响。3.检测前癃通对前列腺组织bc1-2、bax表达的影响。方法:临床研究:对72例病例进行了临床观察。将72例BPH患者,采用随机数字表法分为治疗组和对照组,治疗组40例,口服前癃通胶囊,对照组32例,口服癃闭舒胶囊。观察患者的中医症侯评分,排尿症状评分,生活质量评分,并采用B超检测BPH患者的前列腺体积和膀胱残余尿量,用尿流计测最大尿流率。比较治疗前后两组患者症状及总有效率。实验研究:1.采用组织细胞培养法,体外对BPH患者的前列腺组织块进行培养。2.采用TUNEL法,检测前癃通对体外培养BPH患者前列腺组织细胞凋亡指数的影响。3.采用流式细胞术(FCM),检测前癃通药液对BPH患者前列腺组织细胞周期的影响。4.免疫组化法检测前癃通对体外培养BPH患者前列腺组织bc1-2、bax蛋白表达的影响。5.RT-PCR法检测前癃通对体外培养BPH患者前列腺组织块细胞bc1-2 mRNA、baxmRNA基因表达的影响。结果:临床研究:前癃通胶囊在减轻患者排尿症状、改善生活质量、提高最大尿流率、减少膀胱残余尿量等方面均明显优于癃闭舒(P<0.05),能缩小增生的前列腺体积,与治疗前比较差异有统计学意义(P<0.01)。在临床疗效方面,前癃通胶囊(92.5%)与癃闭舒胶囊(75.0%)相比,差异有统计学意义(P<0.01)。实验研究:1.药物前癃通能促进细胞凋亡,前癃通各剂量组的前列腺细胞凋亡指数都有不同程度上升,与模型组比较,差异有统计学意义(P<0.01),且对细胞凋亡的促进作用表现出明显的量效关系。同时前癃通药液使前列腺组织细胞的G0/G1期细胞数增加,与模型组比较差异具有统计学意义,对细胞周期的影响同样表现出明显的量效关系。2.前癃通高、中剂量组对前列腺组织bc1-2蛋白、bc1-2 mRNA基因的表达有不同程度的抑制作用,对bax蛋白、bax mRNA基因的表达有不同程度的增强作用。结论:1、前癃通胶囊在减轻排尿症状、改善生活质量、提高最大尿流率和减少膀胱残余尿量方面均有显著疗效,并能一定程度的缩小增生的前列腺体积,总疗效优于癃闭舒对照组。2、前癃通对前列腺组织能促进细胞凋亡,同时使细胞周期发生G0/G1期阻滞,抑制bc1-2的基因表达,增强bax的基因表达,从而抑制前列腺增生。

【Abstract】 Objective:1.Observe the clinical curative effect of Qian Long Tong capsule on treating Benign Prostate Hyperplasia(BPH).2.Detect the influence of Qian Long Tong capsule on apoptosis index and cell cycle arresting of the prostatic stromal cells in BPH.3.Explore the influence of Qian Long Tong on the expressions of bax, bcl-2 in prostatic tissue.Methods:Clinical observation:Seventy-two patients of BPH were divided into treatment group and control group according to random word method in the clinical observation.40 cases in treatment group were treated by Qian Long Tong capsule,32 cases in control group were treated by Long Bi Shu capsule.We observed the patients’ scores of tcm symptom, urination symptoms and living quality,tested the patients’ prostate volume and bladder remaining urine by B-ultrasound,and tested maximum urinary flow rate by urine flow meter.Results of the patients’ symptoms and total effective rate were compared before and after treatment. experimental research:1.The prostatic cells of BPH and prostatic tissue mass were cultured in vitro.2.TUNEL was used to examine the effect of Qian Long Tong herb liquor on expressions of apoptosis index.3.Flow cytometry was used to observe the effect of Qian Long Tong herb liquor on cell cycle arresting.4.1mmunity histochemistry analysis was used to explore the influence of Qian Long Tong herb liquor on the expressions of bcl-2 protein and bax protein in prostatic tissue mass.5.RT-PCR was used to examine the effect of Qian Long Tong herb liquor on expressions of bcl-2 mRNA gene and bax mRNA gene.Results:Clinical observation:Qian Long Tong capsule raised the maximum urinary flow rate,improved the living quality,decreased bladder remaining urine,and alleviate sufferings of voiding symptoms,which are all much better than Long Bi Shu capsule(P<0.05).And Qian Long Tong capsule can also reduce the prostate volume of hyperplasia,compared with pre-treatment(P<0.01).There was a very significant difference of the clinical curative effect between the treatment group and the control group(P<0.01).Experimental research:1.Qian Long Tong can promote the cells’ apoptosis.The apoptosis index increased with different degree in different dose groups of Qian Long Tong,and there was a very significant difference among different dose groups with the model group(P<0.01).There seemed to be an obvious dose-dependent relationship.And Qian Long Tong could induce G0/G1 phase arresting and seemed to be dose-dependent.2.During high and medium dose groups of Qian Long Tong,there were different degree of inhibitory action on the expressions of bcl-2 protein and bcl-2 mRNA gene,while enhancement action on the expression of bax protein and bax mRNA gene.Conclusion:1.Qian Long Tong capsule is obviously better than Long Bi Shu capsule in alleviating sufferings of voiding symptoms,improving the living quality,raising the maximum urinary flow rate,and decreasing bladder remaining urine;and Qian Long Tong capsule can reduce the prostate volume of hyperplasia.2.Qian Long Tong can promote the cell’s apoptosis and arrest the G0/G1 phase.And Qian Long Tong can inhibit the expression of bcl-2 gene, enhance the expression of bax gene thus inhibit the hyperplasia of prostate tissue.

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