地奥司明对雄性大鼠良性前列腺增生的改善作用
|
摘要
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),160mg/kg地奥司明能显著抑制AR和ER-α的表达(P<0.01),80mg/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.
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.
引文
[1]Chung K S,Cheon S Y,An H J.Effects of resveratrol on benign prostatic hyperplasia by the regulation of inflammatory and apoptotic proteins[J].J Nat Prod,2015,78(4):689-694.
[2]Wang L,Xie L,Tintani F,et al.Aberrant transforming growth factor-βactivation recruits mesenchymal stem cells during prostatic hyperplasia[J].Stem Cells Transl Med,2017,6(2):394-404.
[3]李玉山.地奥司明药理作用及临床应用研究进展[J].海峡药学,2015,27(12):81-85.
[4]崔功廷,袁铭.地奥司明对盆腔淤血所致大鼠慢性非细菌性前列腺炎的影响[J].解放军医学杂志,2014,39(6):444-447.
[5]Lewinska A,Siwak J,Rzeszutek I,et al.Diosmin induces genotoxicity and apoptosis in DU145 prostate cancer cell line[J].Toxicol in Vitro,2015,29(3):417-425.
[6]黄智超,赵晓昆,王荫槐,等.地奥司明片联合盐酸坦索罗辛缓释胶囊治疗ⅢB型前列腺炎的临床研究[J].临床泌尿外科杂志,2016,31(2):111-114.
[7]刘贻泉.地奥司明治疗中老年前列腺增生的疗效[C].《医药导报》第八届编委会成立大会暨2009年度全国医药学术交流会和临床药学与药学服务研究进展培训班论文集.武汉:中国药理学会、同济医院《医药导报》编辑部,2009:54.
[8]Sun H,Li T J,Sun L N,et al.Inhibitory effect of traditional Chinese medicine Zi-Shen Pill on benign prostatic hyperplasia in rats[J].J Ethnopharmacol,2008,115(2):203-208.
[9]陈镜楼,宋红萍.黄酮类化合物防治良性前列腺增生的作用机制研究进展[J].现代药物与临床,2017,32(11):2287-2290.
[10]Afriyie D K,Asare G A,Bugyei K,et al.Treatment of benign prostatic hyperplasia with croton membranaceus in an experimental animal model[J].J Ethnopharmacol,2014,157:90-98.
[11]Xu D H,Wang L H,Mei X T,et al.Protective effects of seahorse extracts in a rat castration and testosteroneinduced benign prostatic hyperplasia model and mouse oligospermatism model[J].Environ Toxicol Pharmacol,2014,37(2):679-688.
[12]Udensi U K,Tchounwou P B.Oxidative stress in prostate hyperplasia and carcinogenesis[J].J Exp Clin Cancer Res,2016,35(1):139.
[13]Ren H,Li X,Cheng G,et al.The effects of ROS in prostatic stromal cells under hypoxic environment[J].Aging Male,2015,18(2):84-88.
[14]张祥华,马丁.衰老基因在良性前列腺增生发生发展中的研究进展[J].中华临床医师杂志,2013,7(22):10238-10240.
[15]Abdel-Daim M M,Khalifa H A,Abushouk A I,et al.Diosmin attenuates methotrexate-induced hepatic,renal,and cardiac injury:A biochemical and histopathological study in mice[J].Oxid Med Cell Longev,2017,2017:3281670.
[16]Minutoli L,Rinaldi M,Marini H,et al.Apoptotic pathways linked to endocrine system as potential therapeutic targets for benign prostatic hyperplasia[J].Int J Mol Sci,2016,17(8):E1311.
[17]Mirone V,Fusco F,Verze P,et al.Androgens and benign prostatic hyperplasia[J].Eur Urol Suppl,2006,5(4):410-417.
[18]Wu X,Gu Y,Li L.The anti-hyperplasia,anti-oxidative and anti-inflammatory properties of Qing Ye Dan and swertiamarin in testosterone-induced benign prostatic hyperplasia in rats[J].Toxicol Lett,2017(265):9-16.
[19]Wu W F,Maneix L,Insunza J,et al.Estrogen receptorβ,a regulator of androgen receptor signaling in the mouse ventral prostate[J].Proc Natl Acad Sci U S A,2017,114(19):E3816-E3822.
[2]Wang L,Xie L,Tintani F,et al.Aberrant transforming growth factor-βactivation recruits mesenchymal stem cells during prostatic hyperplasia[J].Stem Cells Transl Med,2017,6(2):394-404.
[3]李玉山.地奥司明药理作用及临床应用研究进展[J].海峡药学,2015,27(12):81-85.
[4]崔功廷,袁铭.地奥司明对盆腔淤血所致大鼠慢性非细菌性前列腺炎的影响[J].解放军医学杂志,2014,39(6):444-447.
[5]Lewinska A,Siwak J,Rzeszutek I,et al.Diosmin induces genotoxicity and apoptosis in DU145 prostate cancer cell line[J].Toxicol in Vitro,2015,29(3):417-425.
[6]黄智超,赵晓昆,王荫槐,等.地奥司明片联合盐酸坦索罗辛缓释胶囊治疗ⅢB型前列腺炎的临床研究[J].临床泌尿外科杂志,2016,31(2):111-114.
[7]刘贻泉.地奥司明治疗中老年前列腺增生的疗效[C].《医药导报》第八届编委会成立大会暨2009年度全国医药学术交流会和临床药学与药学服务研究进展培训班论文集.武汉:中国药理学会、同济医院《医药导报》编辑部,2009:54.
[8]Sun H,Li T J,Sun L N,et al.Inhibitory effect of traditional Chinese medicine Zi-Shen Pill on benign prostatic hyperplasia in rats[J].J Ethnopharmacol,2008,115(2):203-208.
[9]陈镜楼,宋红萍.黄酮类化合物防治良性前列腺增生的作用机制研究进展[J].现代药物与临床,2017,32(11):2287-2290.
[10]Afriyie D K,Asare G A,Bugyei K,et al.Treatment of benign prostatic hyperplasia with croton membranaceus in an experimental animal model[J].J Ethnopharmacol,2014,157:90-98.
[11]Xu D H,Wang L H,Mei X T,et al.Protective effects of seahorse extracts in a rat castration and testosteroneinduced benign prostatic hyperplasia model and mouse oligospermatism model[J].Environ Toxicol Pharmacol,2014,37(2):679-688.
[12]Udensi U K,Tchounwou P B.Oxidative stress in prostate hyperplasia and carcinogenesis[J].J Exp Clin Cancer Res,2016,35(1):139.
[13]Ren H,Li X,Cheng G,et al.The effects of ROS in prostatic stromal cells under hypoxic environment[J].Aging Male,2015,18(2):84-88.
[14]张祥华,马丁.衰老基因在良性前列腺增生发生发展中的研究进展[J].中华临床医师杂志,2013,7(22):10238-10240.
[15]Abdel-Daim M M,Khalifa H A,Abushouk A I,et al.Diosmin attenuates methotrexate-induced hepatic,renal,and cardiac injury:A biochemical and histopathological study in mice[J].Oxid Med Cell Longev,2017,2017:3281670.
[16]Minutoli L,Rinaldi M,Marini H,et al.Apoptotic pathways linked to endocrine system as potential therapeutic targets for benign prostatic hyperplasia[J].Int J Mol Sci,2016,17(8):E1311.
[17]Mirone V,Fusco F,Verze P,et al.Androgens and benign prostatic hyperplasia[J].Eur Urol Suppl,2006,5(4):410-417.
[18]Wu X,Gu Y,Li L.The anti-hyperplasia,anti-oxidative and anti-inflammatory properties of Qing Ye Dan and swertiamarin in testosterone-induced benign prostatic hyperplasia in rats[J].Toxicol Lett,2017(265):9-16.
[19]Wu W F,Maneix L,Insunza J,et al.Estrogen receptorβ,a regulator of androgen receptor signaling in the mouse ventral prostate[J].Proc Natl Acad Sci U S A,2017,114(19):E3816-E3822.