【作者】 黄源鹏；

【导师】 杜建；

【作者基本信息】 福建中医学院 ， 中西医结合临床， 2007， 博士

【摘要】 背景：良性前列腺增生（BPH）是中老年男性的常见病、多发病。随着老龄人口日趋增加，良性前列腺增生发病率不断攀升，严重影响着中老年男性的身心健康和生存质量。目的：探讨良性前列腺增生的基本病机，探讨中药康泉方对良性前列腺增生的作用机制与环节以及临床疗效观察，为中医中药治疗良性前列腺增生提供科学的依据。方法1．动物实验：72只SD（Sprague-Dawley）雄性大鼠先随机取12只作为正常组，其余60只采用大鼠去势后皮下注射丙酸睾丸酮致前列腺增生法造模，随机分为：模型组、保列治组、康泉低剂量组、康泉中剂量组、康泉高剂量组。分别灌胃给药30d后，处死大鼠取前列腺组织并测湿重、体积、计算指数；光镜观察组织病理形态学；酶联免疫吸附法检测血清睾丸酮（T）、雌二醇（E₂）含量；免疫组织化学染色法检测前列腺组织Ki-67、bFGF的表达；RT-PCR法检测前列腺组织BaxmRNA、Bcl-2mRNA、PCNAmRNA、bFGFmRNA的表达。2．临床观察：诊断有BPH男性中老年患者60例，随机分为康泉方组、保列治组，疗程12周，观察治疗前后患者国际前列腺症状评分（I-PSS）、生活质量指数（QOL）、中医证候积分、临床症状、最大尿流率（Qmax）、平均尿流率（Qave）、前列腺体积（URV）、残余尿（TPV）等指标。结果1．动物实验：①与模型组比较，康泉高、中剂量组前列腺湿重、体积及指数明显低于模型组（P＜0.05或P＜0.01）；康泉低剂量组前列腺湿重明显低于模型组（P＜0.05）。②大鼠前列腺组织病理表现：模型组有明显增生性改变，康泉各剂量组前列腺组织增生性改变较模型组明显减轻。③与模型组比较，康泉各剂量组血清T含量明显下降（P＜0.05或P＜0.01），康泉中、高剂量组血清E₂含量明显升高（P＜0.05），康泉各剂量组E₂／T比值明显升高（P＜0.05或P＜0.01）。④与模型组比较，康泉各剂量组BaxmRNA表达及Bax／Bcl-2比值明显升高（P＜0.01），Bcl-2mRNA表达明显下降（P＜0.01）。⑤与模型组比较，康泉各剂量组Ki-67蛋白和PCNAmRNA表达明显下降（P＜0.05或P＜0.01）。⑥与模型组比较，康泉各剂量组bFGF蛋白和bFGFmRNA表达均有降低，其中康泉高、中剂量组bFGF蛋白和bFGFmRNA表达明显降低（P＜0.05或P＜0.01），康泉低剂量组bFGF蛋白和bFGFmRNA表达差别无统计学意义（p＞0.05）。2．临床研究：①经治疗12周后，康泉治疗组和保列治对照组均能明显降低BPH患者I-PSS、QOL（P＜0.01）；两组降低I-PSS、QOL差别无显著性（P＞0.05）。治疗组明显降低BPH患者中医症状积分（P＜0.05），对照组降低BPH患者中医症状积分无统计学意义（p＞0.05）；治疗组改善中医症状积分优于对照组（P＜0.05）。②两组均能明显改善BPH患者尿不尽感、尿频、尿中段、尿急、尿线细、排尿费力、夜尿次数症状（P＜0.05或P＜0.01）：治疗组改善尿急、夜尿次数症状优于对照组（P＜0.05）；对照组改善尿不尽症状优于治疗组（P＜0.05）。③两组均能明显提高BPH患者Qmax、Qave（P＜0.05或P＜0.01）；治疗组提高Qmax优于对照组（P＜0.05），两组改善Qave差别无显著性（P＞0.05）。④两组均能明显降低BPH患者URV、TPV（P＜0.05或P＜0.01）；两组降低URV差别无显著性（P＞0.05），对照组降低TPV优于治疗组（P＜0.05），⑤治疗组显效率33.3％，总有效率为80％；对照组显效率26.7％，总有效率为76.7％，两组疗效比较无统计学差异（P＞0.05）。⑥治疗组中瘀血阻滞型显效率38.9％，总有效率为83.3％；肾阳虚衰型显效率25％，总有效率为75％。瘀血阻滞型和肾阳虚衰型疗效比较无统计学差异（P＞0.05）。结论1．肾虚是BPH发病的根本原因，血瘀为BPH的重要病理变化，热毒内蕴为BPH的主要兼证，久病入络是BPH缠绵难愈的重要病机。BPH的基本病机为本虚标实，具体表现为肾虚瘀血热毒痹阻，久病则入络。2．康泉方对实验性BPH大鼠的治疗作用是多环节、多靶点的。其能够降低实验性BPH大鼠前列腺湿重、体积、指数；能够改善实验性BPH大鼠前列腺组织病理增生性改变；能够改善实验性BPH大鼠血清雌雄激素水平的紊乱：能够调节实验性BPH大鼠前列腺组织BaxmRNA及Bcl-2mRNA表达平衡，促进前列腺细胞凋亡；能够降低实验性BPH大鼠前列腺组织Ki-67蛋白和PCNAmRNA表达，抑制前列腺细胞增殖；能够降低实验性BPH大鼠前列腺组织bFGF蛋白及bFGFmRNA表达。3．康泉方能够降低BPH患者国际前列腺更多还原

【Abstract】 Backgroud: Benign prostatic hyperplasia（BPH） is a common and frequently occurringdisease in middle and older male. While the aging population in our country increasinggradually, the incidence of BPH also increases correspondingly, BPH has alreadyaffected the health and the quality of life.Objectives: To probe into the Traditional chinese medical（TCM） Pathologensis ofBPH. To investigate the mechanism of Kangquan Recipe（KQR） on BPH and observe clinicaleffect in ordor to provide data for Traditional Chinese Medical and Pharmacy on BPH.Methods:（1）animal experiment: 72 Sprague-Dawley male rats were randomly dividedinto six groups:normal group, model group, finasteride group, KQR low-dosage group,KQR medium-dosage group, KQR large-dosage group. Except for normal group, BPH modelrats of the rest groups were established by subcutaneously injecting testosteronepropionate after being castrated. The rats were killed and prostate glands wereremoved after intragastric administration respectively for 30 days.Theweight, volume and index of the prostate were measured. The pathomorphological changeswere examined under lightmicroscope. By means of enzyme linked immunosorbent assay（ELISA）,the plasma levels of testosterone（T） and estradiol（E₂） were examined. Bymeans of immunohistochemisty, the expressions of Ki-67 and bFGF were examined in theprostates of rats. By means of RT-PCR, the expressions of BaxmRNA, Bcl-2mRNA, PCNAmRNAand bFGFmRNA were examined in the prostates of rats. （2）clinical study:60 middle and older male cases of BPH were randomly divided into two groups: KQR groug andFinasteride group. The cases were treated respectively by KQR and Finasteride for12 weeks. Changes of international prostate symptom scores （I-PSS）, quality oflife（QOL）, TCM symptomatic scores, clinical symptoms, maximun flow rate（Qmax）, averageflow rate（Qave）, residual urine volume（RUV）, total prostatic volume （TPV） in patientswith BPH were observed before and after treatment.Results:（1）animal experiment:①Compared with model group, prostaticweights, volumes and indexs decreased significantly in KQR large, medium-dosagegroups （P＜0.05 or P＜0.01） and prostatic weights decreased significantly in KQRlow-dosage group （P＜0.05）.②Model rats had obvious anomaly in pathomorphology,KQR can restrain the hyperplasia of prostate.③Compared with model group, the levelsof testosterone decreased significantly in all KQR treatment groups （P＜0.05 orP＜0.01）, the levels of estradiol increased significantly in KQR large, medium-dosagegroup （P＜0.05）, the ratios of E₂/T increased significantly in all KQR treatment groups（P＜0.05 or P＜0.01）.④Compared with model group, the expressions of BaxmRNA andratios of Bax/Bcl-2 increased significantly, the expressions of Bcl-2mRNA decreasedsignificantly in all KQR treatment groups （P＜0.01）.⑤Compared with model group,the expressions of Ki-67 and PCNAmRNA decreased significantly in all KQR treatmentgroups （P＜0.05 or P＜0.01）.⑥Compared with model group, the expressions of bFGFand bFGFmRNA decreased in all KQR treatment groups, the expressions of bFGF andbFGFmRNA decreased significantly in KQR large, medium-dosage groups （P＜0.05 orP＜0.01）, but the expressions of bFGF and bFGFmRNA in KQR low-dosage group had nosignificantly differece （P＞0.05）. （2）clinical study:①After treatment for 12weeks, the levels of I-PSS and QOL in patients with BPH were reduced significantlyin the treated group by KQR and the control group by finasteride （P＜0.01）.In respect of reducing the levels of I-PSS and QOL, KQR and finasteride had no significantlydifference （P＞0.05）. KQR reduced significantly the levels of TCM symptomatic scores（P＜0.05）, finasteride reduced the levels of TCM symptomatic scores but notsignificantly （P＞0.05）, KQR reduced the levels of TCM symptomatic scores superiorto finasteride （P＜0.05）②KQR and finasteride ameliorated significantly the symptomsof imcomplete emptying, frequency, intermittency, urgency, weak stream, hesitancy andnocturia （P＜0.05 or P＜0.01）,KQR ameliorated the symptoms of urgency and nocturiasuperior to finasteride （P＜0.05）, finasteride ameliorated the symptoms of imcompleteemptying superior to KQR （P＜0.05）.③KQR and finasteride improved significantly thelevels of Qmax and Qave, KQR improved the levels of Qmax superior to finasteride（P＜0.05）.In respect of improving the levels of Qave, KQR and finasteride had nosignificantly difference （P＞0.05）.④KQR and finasteride reduced significantly thelevels of URV and TPV. In respect of reducing the levels of URV, KQR and finasteridehad no significantly difference （P＞0.05）.Finasteride decreased the levels of TPVsuperior to KQR （P＜0.05）.⑤The markedly effective rate, total effective rate inthe treated group was 33.3%,80% respectively. The markedly effective rate, totaleffective rate in the control group was 26.7%,76.7% respectively. The curativeeffects of both groups had no significantly difference （P＞0.05）.⑥The markedlyeffective rate, total effective rate in the group of stagnation of blood stasis was38.9%,83.3% respectively. The markedly effective rate, total effective rate in thegroup of decline of kidney-Yang was 25%,75% respectively. The curative effects ofthe groups of stagnation of blood stasis and decline of kidney-Yang had nosignificantly difference in the treated group （P＞0.05）.Conclusion:①The study has suggested that kidney weak is the fundamentalreason, blood stasis is the important pathological change, interior retention of heat and toxin is the main concurrent Symptom, prolonged illness obstructing thecollaterals is the important pathogenesis of BPH.②KQR shows multiway andmultitarget treatment effects on benign prostatic hyperplasia in experimental rats.KQR can effectively decrease prostatic weights, volumes and indexs, restrain thepathological hyperplasia of prostate, regulate the balance of plasma estradiol andtestosterone, regulate the expressions of baxmRNA and bcl-2mRNA so that they canpromote the cell apoptosis of prostate, decrease the expressions of Ki-67 and PCNAmRNAso that they can restrain the cell proliferation of prostate, decrease theexpressions of bFGF and bFGFmRNA in prostate of experimental rats.③KQR caneffectively reduce the levels of I-PSS and ameliorate quality of life, reduce thelevels of TCM symptomatic scores, ameliorated the symptoms of imcompleteemptying, frequency, intermittency, weak stream, urgency, hesitancy andnocturia, improve the levels of Qmax and Qave, reduce the levels of URV and TPV.④KQR promote the cell apoptosis superior to finasteride, but finasteride restrainthe cell proliferation and the expressions of bFGF superior to KQR in the prostatesof experimental rats. KQR reduce the levels of TCM symptomatic scores, improve thelevels of Qmax, ameliorate the symptoms of weak stream and nocturia superior tofinasteride, but finasteride reduce the levels of TPV, ameliorate the symptom ofimcomplete emptying superior to KQR in patients with BPH. above shows that KQR hasits characteristic and good prospects on BPH.Subjective headings: benign prostatic hyperplasia/tcd ther, cell apoptosis/drugeff, cell proliferation/drug elf, growth factor/drug eff, rat, male, @ KangquanRecipe更多还原