藏药“依蒙”5种基原植物抗良性前列腺增生活性的研究

Studies on Anti-prostatic Hyperplasia Activity of Five Medicinal Plants Traditionally Named as Tibetan Medicine “Yimeng”

目的比较藏药"依蒙"5种基原植物长花铁线莲、甘川铁线莲、甘青铁线莲、美花铁线莲、黄花铁线莲对良性前列腺增生(BPH)模型小鼠的治疗作用和可能的作用机制,为探讨各基原药材间替代使用的合理性奠定基础。方法采用皮下注射丙酸睾酮(TP)致小鼠BPH模型,用上述5种植物提取物不同剂量分组灌胃,观察其对模型小鼠前列腺指数(prostate index,PI)和前列腺组织形态结构的影响,检测BPH模型小鼠血清中睾酮(testosterone,T)、双氢睾酮(dihydrotestosterone,DHT)、雌二醇(estradiol,E2)、前列腺酸性磷酸酶(prostatic acid phosphatase,PAP)水平,并通过测定前列腺组织中促细胞凋亡因子(BCL-2 associated x protein,BAX)mRNA、抑制性凋亡因子(B-cell lymphoma-2,BCL-2)mRNA、表皮生长因子(epidermal growth factor,EGF)mRNA及其受体(epidermal growth factor receptor,EGFR)mRNA表达,探讨其可能的作用机制。结果仅长花铁线莲和美花铁线莲可明显降低BPH模型小鼠前列腺指数(P<0.05,P<0.01),改善前列腺组织的病理学形态。此外,美花铁线莲高剂量组明显降低BPH模型小鼠血清中PAP、DHT、E2、T水平(P<0.01);高、低剂量组均能明显降低BCL-2 mRNA表达(P<0.01,P<0.001),低剂量组可提高BAX mRNA表达(P<0.05),高、低剂量组均能明显降低EGF mRNA表达(P<0.001)。长花铁线莲高剂量组亦可明显降低BPH小鼠血清中PAP、DHT、E2水平(P<0.01),降低T水平(P<0.05);高、低剂量组均能明显提高前列腺组织中BAX mRNA表达(P<0.01),明显降低BCL-2 mRNA表达(P<0.01),明显降低EGF mRNA表达(P<0.001)。显示二者均可通过调节性激素水平,以及降低EGF表达,减少EGF与EGFR的结合率减少前列腺上皮细胞增生,同时增加细胞凋亡,促进前列腺细胞数量减少,缩小前列腺体积来缓解BPH模型小鼠的病理形态。结论5种"依蒙"基原植物对BPH小鼠的治疗作用差异明显,美花铁线莲与长花铁线莲对BPH小鼠的治疗作用明显优于其他3种,且作用机制相同,提示各基原植物互相替代使用治疗BPH的合理性值得商榷。

Objective To investigate the anti-prostatic hyperplasia effects and mechanisms of five species of Clematis,so as to confirm whether they can be used alternatively.These plants includes C.rehderiana,C.akebioides,C.tangutica,C.potaninii,and C.intricate.Methods The benign prostatic hyperplasia(BPH)model of mouse was induced by subcutaneous injection of testosterone propionate(TP).The effects of the five plant extracts on the prostate index(PI),estradiol(E2),prostatic acid phosphatase(PAP),serum testosterone(T)and dihydrotestosterone(DHT)were detected,and the levels of BCL-2 associated x(BAX)mRNA,B-cell lymphama-2(BCL-2)mRNA,epidermal growth factor(EGF)mRNA and its receptor(EGFR)mRNA expression levels were detected as well as the pathological changes in prostate tissue were examined.Results Only the extracts of two plants,C.potaninii.and C.rehderiana,could significantly reduce the PI of BPH model mice(P<0.05,P<0.01),and improve the pathological morphology of prostate tissue.Their possible mechanism are as follows.The extracts of C.potaninii.reduced the serum PAP,DHT,E2 and T levels of BPH model mice(P<0.01),and significantly reduced the BCL-2 mRNA(P<0.01,P<0.001),EGF mRNA(P<0.001)expression in the prostate tissue of BPH model mice,and increase the BAX mRNA(P<0.05)expression in the prostate tissue of BPH model mice.The extracts of C.rehderiana could also reduce the serum PAP,DHT,E2(P<0.01)and T(P<0.05)levels of BPH model mice,significantly reduce BCL mRNA(P<0.01)and EGF mRNA(P<0.001)expression in prostate tissue of BPH model mice,increase the expression of BAX mRNA(P<0.01)in prostate tissue of BPH model mice.The mechanism may be related to modulation of serum sex hormones levels and down-regulating EGF expression of BHP mice;it is associated with the high apoptosis rate and low proliferation rate of prostate,reduction of the prostate gland volume,to alleviate the morphologic pathology,too.Conclusion The therapeutic effects of five Clematis species on BPH were significantly different.The therapeutic effect of C.rehderiana and C.potaninii.on BPH mice were significantly better than the other three species,and their mechanism of action are the same.It was preliminarily shown that the rationality of alternative use of each other of these medicinal plants traditionally named as Tibetan Medicine"Yimeng"for BPH are questionable.