桂枝茯苓胶囊抗良性前列腺增生作用机制研究  

Study on mechanism of Guizhi Fuling Capsule treating benign prostatic hyperplasia

作　　者：张亚萍[1] 王红梅[2] 谢雪[2] 肖伟[2] 王振中[2] ZHANG Yaping;WANG Hongmei;XIE Xue;XIAO Wei;WANG Zhenzhong(College of Medicine,Nanjing University of Chinese Medicine,Nanjing 210046,China;Jiangsu Kanion Pharmaceutical Co.,Ltd.,Lianyungang 222001,China)

机构地区：[1]南京中医药大学药学院,江苏南京210046 [2]江苏康缘药业股份有限公司,江苏连云港222001

出　　处：《药物评价研究》2023年第7期1472-1479,共8页Drug Evaluation Research

基　　金：2021年国家中医药管理局岐黄学者项目(国中医药人教函[2022]6号)。

摘　　要：目的 探讨桂枝茯苓胶囊对大鼠良性前列腺增生(BPH)的作用机制。方法 72只雄性SPF级SD大鼠随机分为6组:对照组、模型组、非那雄胺(阳性药,2 mg·kg^(-1))组和桂枝茯苓胶囊低、中、高剂量(0.87、1.74、3.47 g·kg^(-1))组,每组12只;除对照组外,其余5组sc雌、雄激素(0.05 mg·kg^(-1)苯甲酸雌二醇和4 mg·kg^(-1)丙酸睾酮),每天1次,连续28 d,建立BPH模型。同时ig给予药物,每天给药1次,连续给药28 d。HE染色观察前列腺组织病理变化;ELISA法检测血清中双氢睾酮(DHT)、雌二醇(E2)和前列腺中DHT、E2、转化生长因子β1(TGF-β1)、表皮生长因子(EGF)的水平;Western blotting检测前列腺中增殖细胞核抗原(PCNA)、雄激素受体(AR)、雌激素受体α (ERα)、胰岛素样生长因子(IGF-1)、成纤维细胞生长因子7(FGF-7)、缺氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)蛋白表达水平;实时荧光定量PCR(qRT-PCR)法检测前列腺中PCNA、FGF-7、IGF-1和VEGF mRNA表达水平。结果 与对照组比较,模型组前列腺指数显著增加(P<0.01),前列腺上皮厚度显著增加(P<0.01),前列腺显著增生,间质充血、水肿;血清中DHT和前列腺中DHT、E2、EGF水平显著升高(P<0.05、0.01);前列腺中TGF-β1水平显著降低(P<0.05),PCNA、AR、 ERα、 FGF-7、 IGF-1、 HIF-1α和VEGF蛋白表达水平及PCNA、 FGF-7、 IGF-1和VEGFmRNA表达水平显著升高(P<0.05、0.01)。与模型组比较,桂枝茯苓胶囊高剂量显著降低前列腺指数(P<0.05),各剂量均显著减小前列腺上皮厚度(P<0.01),减轻间质充血、水肿;桂枝茯苓胶囊低剂量显著升高前列腺中TGF-β1水平,显著降低EGF水平(P<0.05)以及PCNA、FGF-7、VEGF mRNA的表达(P<0.01),显著下调前列腺中AR蛋白表达水平(P<0.05);中剂量能显著升高前列腺中TGF-β1水平,显著降低EGF水平(P<0.05、0.01)以及PCNA、VEGF mRNA的表达水平(P<0.01),显著下调IGF-1蛋白表达水平(P<0.05);高剂量显著升高前列腺中TGF-β1Objective To explore the mechanism of Guizhi Fuling capsule on benign prostatic hyperplasia(BPH) in rats.Methods 72male SPF SD rats were randomly divided into six groups:control group,model group,finasteride(positive drug,2 mg·kg^(-1)) and Guizhi Fuling Capsules low-dose,medium-dose and high-dose(0.87,1.74,3.47 g·kg^(-1)) groups,with 12 rats in each group.Except the control group,the other five groups were given male and female hormones(0.05 mg·kg^(-1) estradiol benzoate and 4 mg·kg^(-1)testosterone propionate),once a day for 28 d,and the BPH model was established.At the same time,the therapeutic drug was given by ig,with a volume of 10 mL·kg^(-1),once a day,for 28 d.The pathological changes of prostate tissue were observed by HE staining.The contents of DHT and E2 in serum,DHT,E2,TGF-β1 and EGF in prostate tissue were detected by ELISA.The protein expressions of PCNA,AR,ERα,IGF-1,FGF-7,HIF-1α and VEGF in prostate were detected by Western blotting.The mRNA expression of PCNA,FGF-7,IGF-1 and VEGF in prostate was detected by qRT-PCR.Results Compared with control group,the prostate index and epithelial thickness of prostate in the model group were significantly increased(P<0.01),the prostatic hyperplasia,interstitial congestion and edema were significantly increased,and the contents of DHT in serum and DHT,E_(2) and EGF in prostate were significantly increased(P<0.05 and 0.01).The content of TGF-β1 in prostate was significantly decreased(P<0.05),and the protein expression levels of PCNA,AR,ERα,FGF-7,IGF-1,HIF-1α and VEGF and the mRNA expression levels of PCNA,FGF-7,IGF-1 and VEGF in prostate were significantly increased(P<0.05 and 0.01).Compared with the model group,the high-dose group of Guizhi Fuling Capsule significantly reduced the prostate index(P<0.05),while the low-dose,medium,and highdose groups significantly reduced the thickness of the prostate epithelium(P<0.01),reducing prostate hyperplasia,interstitial congestion,and edema.The low-dose group of Guizhi Fuling Capsule significantly increased TG

关 键 词：良性前列腺增生 桂枝茯苓胶囊 生长因子 激素 增殖 血管生成 

分 类 号：R285.5[医药卫生—中药学]