黄酮哌酯对前列腺增生模型大鼠的保护作用机制研究

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（miR-21）和转化生长因子β1（TGF-β1）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、miR-21、TGF-β1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、miR-21、TGF-β1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miR-21和TGF-β1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<0.05). Compared with model group,the precipitation of prostatic collagen was decreased;prostatic in-dex,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.