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前癃通胶囊对良性前列腺增生的临床观察和大鼠前列腺IGF-ⅠmRNA/IGF-ⅠRmRNA、Fas/Fas1表达的影响

Clinical Observation on Treatment of Benign Prostatic Hyperplasia with Qianlong Tong Capsule and Experimental Study of the Influence of It on Expression of IGF-ⅠmRNA/IGF-ⅠRmRNA and Fas/Fas1 of Prostate in Rats Model

【作者】 雷学成

【导师】 贺菊乔;

【作者基本信息】 湖南中医药大学 , 中西医结合外科学, 2011, 博士

【摘要】 背景:良性前列腺增生是中老年男性的常见病、多发病。随着老龄人口日趋增加,良性前列腺增生的发病率不断攀升,其已成为严重影响中老年男性身心健康和生活质量的重大疾病。目的:观察前癃通胶囊治疗良性前列腺增生的临床疗效,探讨良性前列腺增生的基本病机以及前癃通胶囊对良性前列腺增生的作用机制,为前癃通胶囊治疗良性前列腺增生提供科学依据,以便更好地推广应用。方法:1.临床观察:74例良性前列腺增生患者,随机分为治疗组37例和对照组37例,治疗组口服前癃通胶囊,对照组口服前列舒乐胶囊。观察患者治疗前后国际前列腺症状评分(Ⅰ-PSS)、生活质量(QOL)评分、最大尿流率(Qmax)、平均尿流率(Qave)、膀胱残余尿(RUV)、中医症状评分和前列腺体积(PV)等的变化。2.动物实验:72只SD雄性大鼠随机分为6组:正常组、模型组、前列舒乐胶囊组、前癃通胶囊低剂量组、前癃通胶囊中剂量组和前癃通胶囊高剂量组,每组12只。除正常组外,其余大鼠去势后皮下注射丙酸睾丸酮致前列腺增生法造模。分别灌胃给药30d后,处死大鼠取出前列腺并测湿重、体积和计算指数;RT-PCR法检测前列腺组织IGF-ⅠmRNA、IGF-ⅠRmRNA (?)勺表达;免疫组织化学染色法检测前列腺组织Fas、Fas1的表达。结果:1.临床研究:①前癃通胶囊治疗组和前列舒乐胶囊对照组均能明显降低BPH患者Ⅰ-PSS和QOL评分(P<0.01);前癃通胶囊组降低Ⅰ-PSS、QOL评分优于前列舒乐胶囊组(P<0.05)。②两组均能明显提高BPH患者Qmax、Qave(P<0.01),前癃通胶囊组优于前列舒乐胶囊组(P<0.05)。③两组均能明显降低BPH患者RUV、PV(P<0.01),前癃通胶囊组优于前列舒乐胶囊组(P<0.05)。④两组均能明显缩小BPH患者前列腺内腺纵径(P<0.05),前癃通胶囊组和前列舒乐胶囊组无明显差异(P>0.05)。⑤两组均能明显改善BPH患者排尿困难、夜尿次数、尿线情况、倦怠乏力和少腹症状(P<0.01);前癃通胶囊组改善排尿困难、夜尿次数、尿线情况优于前列舒乐胶囊组(P<0.05);两组改善倦怠乏力和少腹症状无差异(P>0.05)。⑥前癃通胶囊组显效率61.8%,总有效率为88.2%;对照组显效率32.3%,总有效率为74.2%;前癃通胶囊组疗效优于前列舒乐胶囊组((P<0.05)。⑦两组对治疗前后血清总前列腺特异性抗原(tPSA)和勃起功能国际指数(IIEF-5)评分均无明显影响。2.实验研究:①前癃通各剂量组、舒乐组大鼠前列腺湿重、体积和指数均小于模型组(P<0.01);前癃通高剂量组降低前列腺湿重、体积和指数优于舒乐组(P<0.05)。②前癃通各剂量组、舒乐组大鼠前列腺组织IGF-ⅠmRNA、IGF-ⅠRmRNA的表达明显低于模型组(P<0.01);前癃通高剂量组大鼠前列腺组织IGF-ⅠmRNA、IGF-ⅠRmRNA的表达低于前列舒乐组(P<0.05)。③前癃通各剂量组、舒乐组大鼠前列腺组织Fas、Fas1蛋白的表达明显高于模型组(P<0.01);前癃通高剂量组大鼠前列腺组织中Fas、Fas1的表达高于舒乐组(P<0.05)。结论:·1.气虚血瘀是BPH的基本病机,益气活血、利水消癥为治疗大法。2.前癃通胶囊能降低BPH患者国际前列腺症状评分和生活质量评分,提高最大尿流率和平均尿流率,减少膀胱残余尿量,改善中医症状和缩小前列腺体积。3.前癃通胶囊能够降低实验性BPH大鼠前列腺湿重、体积和指数;能够降低实验性BPH大鼠前列腺组织IGF-ⅠmRNA、IGF-ⅠRmRNA的表达;能够提高实验性BPH大鼠前列腺组织Fas、FasⅠ的表达。实验结果提示,前癃通胶囊治疗良性前列腺增生的作用是多环节、多靶点的,影响前列腺组织IGF-ⅠmRNA、IGF-ⅠRmRNA和Fas、Fas1的表达可能是其中的机理之一

【Abstract】 Backgroud:Benign prostatic hyperplasia(BPH) is a common and frequently occurring disease of senile male. With the growing number of aged population,the incidence of BPH is also rising. BPH has become a major disease with serious influence on senile male’s physical and mental health and quality of life.Objective:To investigate the clinical effect and mechanism of Qianlong Tong Capsule(QLTC) on BPH, to probe into the traditional chinese medical pathogenesis of BPH and support the capsule with scientific basis, so as to be better popularized and applied. Methods:1. Clinical study:74 cases of BPH were randomly divided into treatment group and control group. The cases were treated respectively by Qianlong Tong Capsule (QLTC) and Qianlie Shule Capsule (QLSLC) for 3 months. Changes of international prostate symptom scores (Ⅰ-PSS), quality of life(QOL) seores, TCM symtomatic scores, maximun flow rate(Qmax), average flow rate (Qave), bladder residual urine (RUV), and total prostate volume (PV) in patients with BPH were observed before and after treatment.2. Animal experiment:72 SD male rats were randomly divided into six groups:normal group, model group, QLSLC group, QLTC low-dosage group, QLTC medium-dosage group, QLTC large-dosage group. Except for normal group, rats of the rest groups were established by subcutaneously injecting testosterone propionate after being castrated. The rats were killed and prostate glands were removed after intragastric achainistration respectively for 30 days. The weight, volume and index of the prostate were measured.By means of RT-PCR, the expressions of IGF-ⅠmRNA、IGF-ⅠRmRNA were examined in the prostates of rats. By means of immunohistochemisty the expressions of Fas, Fasl were examined in the prostates of rats. Results:1. Clinical study:After 3 months’treatment,①the levels ofⅠ-PSS and QOL seores in patients with BPH were reduced significantly in the treated group by QLTC and the control group by QLSLC(P<0.01). In respect of reducing the levels ofⅠ-PSS and QOL seores, QLTC superior to QLSLC (P<0.05).②QLTC and QLSLC improved significantly the levels of Qmax and Qave(P<0.01), QLTC superior to QLSLC(P<0.05).③QLTC and QLSLC reduced significantly the levels of RUV and PV (P<0.01), QLTC superior to QLSL (P<0.05).④QLTC and QLSLC reduced the longitudinal diameter of prostate significantly(P<0.05), but QLTC and QLSLC had no significantly difference (P>0.05).⑤QLTC and QLSLC reduced significantly the levels of dysuria, nocturia number, urine line, languid, the lower abdomen symptoms seores (P<0.01). QLTC reduced the levels of dysuria, urine line and nocturia number seores superior to QLSLC (P<0.05). But QLTC reduced the levels of languid, the lower abdomen symptoms seores had no significantly difference to QLSLC (P>0.05).⑥The markedly effective rate, total effective rate in the treated group was 61.8%,88.2% respectively, the markedly effective rate, total effective rate in the control group was 32.3%,74.2% respecti-vely. The curative effects of QLTC superior to QLSLC(P<0.05). ⑦QLTC and QLSLC both have little influence on tPSA and IIEF-5(P>0.05).2. Animal experiment:①Copared with model group, prostatic weights, volumes and indexs decreased significantly in all of QLTC group and QLSLC group(P<0.01). Prostatic weights, volumes and indexs in QLTC large-dosage groups were less than QLSLC group (P<0.05).②Compared with model group, the expressions of IGF-ⅠmRNA and IGF-ⅠRmRNA decreased signifieantly in all QLTC and QLSLC groups(p<0.01). Compared with QLSLC, the expressions of IGF-ⅠmRNA and IGF-ⅠRmRNA in QLTC large-dosage groups groups decreased significantly (p<0.05).③The expressions of Fas and Fasl in QLTC varied dose group and QLSLC group were significantly more than model group (p<0.01), the expressions of Fas and Fasl in QLTC were significantly more than QLSLC group (p<0.05).Conclusions:1. Deficiency of Qi and blood stasis is the basic pathogenesis of BPH. The treatment of invigorating Qi and promoting blood flow and Lishui Xiaozheng were selected.2.QLTC can effectively reduce the levels ofⅠ-PSS and ameliorated quality of life, improve the levels of Qmax and Qave, redue the levels of RUV, ameliorat the symptom of TCM, lessen PV.3. QLTC shows multiway and multitarget treatment effects on BPH in experimental rats. QLTC can effectively decrease prostatic weights, volumes and indexs, decrease the expressions of IGF-ⅠmRNA and IGF-ⅠRmRNA, increase the expressions of Fas and Fasl in experimental rats. Experimental results indicated that the treatment of QLTC on benign prostatic hyperplasia is many links and targets, influence of the expression of IGF-ⅠmRNA、IGF-ⅠRmRNA、Fas and Fasl in prostate tissue might be one of the mechanisms.

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