目的 探讨地奥司明对大鼠良性前列腺增生的改善作用及其作用机制。方法 Wistar大鼠随机分为对照组、模型组、地奥司明80、160 mg/kg组，每组各6只。采用手术去势和每日sc 10 mg/kg的丙酸睾酮注射液建立大鼠良性前列腺增生模型，地奥司明组每日ig 80、160 mg/kg地奥司明，各组大鼠连续给药4周。实验结束后分离前列腺组织，观察药物对良性前列腺增生大鼠前列腺指数（PI）、PACP酶活力、前列腺组织形态学变化和前列腺组织氧化应激水平的影响，并采用Western blotting法评价I型胶原（Col-I）、雄激素受体（AR）和雌激素受体-α/β（ER-α/β）表达。结果 与模型组比较，地奥司明能够显著降低PI（P<0.01），抑制PACP的酶活力（P<0.05、0.01）。与模型组比较，地奥司明在一定程度抑制了前列腺上皮增生和胶原沉积。与模型组比较，地奥司明组（160、80 mg/kg）均能显著提升超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和过氧化氢酶（CAT）的酶活力（P<0.05、0.01）。与模型组比较，地奥司明干预可有效升高前列腺还原型谷胱甘肽（GSH）、总巯基（T-SH）水平，降低丙二醛（MDA）、氧化型谷胱甘肽（GSSG）水平（P<0.05、0.01）。与模型组比较，地奥司明组Col-I的表达明显降低（P<0.01、0.05），160 mg/kg地奥司明能显著抑制AR和ER-α的表达（P<0.01），80 mg/kg地奥司明则明显降低AR的表达（P<0.05）；且地奥司明能显著提高ER-β的表达（P<0.01）。结论 地奥司明改善大鼠良性前列腺增生的作用机制与调控前列腺AR、ER-α/β表达和氧化应激有关。

Objective To investigate the improvement and mechanism of diosmin on benign prostatic hyperplasia in male rats. Methods Wistar rats were randomly divided into the control, model, and diosmin (80, 160 mg/kg) groups, and each group had 6 rats. Rats with benign prostatic hyperplasia model were established by surgical castration, and sc administered with Testosterone Propionate Injection 10 mg/kg. The diosmin groups were ig administered with diosmin 80 and 160 mg/kg every day, and the rats in each group were given the drug continuously for 4 weeks. The prostate tissue was isolated, and the effects of drugs on prostate PI, PACP activity, prostate tissue morphology, and oxidative stress level were observed. And the Col-I, AR, and ER-α/β expression levels were evaluated by Western blotting method. Results Compared with the model group, PI was significantly reduced in the diosmin groups (P<0.01), and the enzyme activity of PACP was inhibited (P<0.05, 0.01). Compared with the model group, diosmin inhibited prostatic epithelial hyperplasia and collagen deposition to a certain extent. Compared with the model group, the activities of SOD, GPx, and CAT were significantly increased in the diosmine 80, 160 mg/kg groups (P<0.05, 0.01). Compared with the model group, the intervention of diosmin could significantly increase GSH and T-SH levels in the prostate, and reduce the MDA and GSSG levels (P<0.05, 0.01). Compared with the model group, the expression of Col-I in the diosmin group was significantly decreased (P<0.01, 0.05), and the expression levels of AR and ER-α were significantly inhibited by 160 mg/kg diosmin (P<0.01), the expression level of AR was significantly decreased by 80 mg/kg diosmin (P<0.05), and the expression level of ER-β was significantly increased by dexamethasone (P<0.01). Conclusion The mechanism of diosmin in improving benign prostatic hyperplasia in rats is related to regulation of AR, ER-alpha/beta expression and oxidative stress in the prostate.

武汉市临床医学科研项目（WZ17Q05）