黄酮哌酯对前列腺增生模型大鼠的保护作用机制研究  

Study on the Protective Mechanism of Flavoxate on Prostatic Hyperplasia in Model Rats

作　　者：杜丽芬[1] 陈镜楼[1] 

机构地区：[1]华中科技大学同济医学院附属普爱医院药学部,武汉430033

出　　处：《中国药房》2016年第31期4357-4359,共3页China Pharmacy

基　　金：湖北省自然科学基金资助项目(No.2015CFB250);武汉市中青年医学骨干人才培养工程(武卫生计生通[2015]9号)

摘　　要：目的:研究黄酮哌酯对前列腺增生(BPH)模型大鼠的保护作用机制。方法:将大鼠随机分为假手术组、模型组和黄酮哌酯高、低剂量组(80、40 mg/kg),每组8只。除假手术组外,其余各组大鼠通过去势和注射丙酸睾酮复制BPH模型,丙酸睾酮注射1 h后每组大鼠ig相应药物,每日1次,连续4周。末次给药后,考察前列腺指数;采用天狼星红和Masson染色检测前列腺胶原沉积;免疫组化检测前列腺Ⅰ型胶原、纤维连接蛋白(FN)和上皮钙黏着蛋白(E-cadherin)的表达;酶联免疫吸附法检测前列腺组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GPx)、丙二醛(MDA)、表皮生长因子(EGF)和血管内皮生长因子(VEGF)的水平;实时荧光定量聚合酶链反应法检测微小RNA21(mi R-21)和转化生长因子β_1(TGF-β_1)水平。结果:与假手术组比较,模型组大鼠前列腺胶原沉积增多,前列腺指数、FN表达、MDA含量和VEGF、EGF、mi R-21、TGF-β_1水平均升高(P<0.05),E-cadherin表达、SOD和GPx活力均降低(P<0.05)。与模型组比较,黄酮哌酯高、低剂量组大鼠前列腺胶原沉积减少,前列腺指数、FN表达、MDA含量和VEGF、EGF、mi R-21、TGF-β_1水平均降低(P<0.05),E-cadherin表达、SOD和GPx活力均升高(P<0.05)。结论:黄酮哌酯抗BPH的机制可能与下调mi R-21和TGF-β_1表达,抑制氧化应激和血管生成,改善上皮-间质转化有关。OBJECTIVE： To study the protective mechanism of flavoxate on prostatic hyperplasia in model rats. METHODS： The rats were randomly divided into sham operation group, model group and flavoxate high-dose and low-dose groups （80, 40 mg/kg）, with 8 rats in each group. Except for sham operation group, those groups were emasculated and given sterandryl to induce BPH model. They were given relevant medicine intragastrically 1 h after administration of sterandryl, once a day, for consecutive 4 weeks. Sirius red and Masson staining were used to detect the precipitation of collagen in prostate; immunohistochemistry was used to detect the expressions of prostatic type I collagen, FN and E-cadherin; ELISA assay was used to determine the levels of SOD, GPx, MDA, EGF and VEGF in prostate, qPCR assay was used to detect the levels of miR-21 and TGF-β1. RESULTS： Compared with the sham operation group, the prostatic collagen was accumulated; prostatic index, the expression of FN, MDA content and levels of VEGF, EGF, miR-21 and TGF-β1 were increased （P〈0.05） ; the expression of E-cadherin, and the activity of SOD and GPx were decreased （P〈0.O5）. Compared with model group, the precipitation of prostatic collagen was decreased; prostatic index, the expression of FN, MDA content, the levels of VEGF, EGF, miR-21 and TGF-β1 were decreased in flavoxate high-dose and low-dose groups （P〈0.05） ; while the expression of E-cadherin and the activity of SOD and GPx were increased （P〈0.05）. CONCLUSIONS： Flavoxate can inhibit BPH, the mechanism of which may associated with down-regulating the expressions of miR-21 and TGF-β1, inhibiting oxidative stress and angiogenesis and improving epithelial-mesenchymal transition.

关 键 词：黄酮哌酯 前列腺增生 氧化应激 血管生成 上皮-间质转化 大鼠 

分 类 号：R965[医药卫生—药理学]