Echinacoside and Cistanche tubulosa(Schenk) R. wight have male reproductive protection effect by targeting hypothalamic and rogen receptor

OBJECTIVE Cistanche deserticola Y.C.Ma is an official plant that grows in arid or semi-arid areas.Our early work demonstrated that Cistanche extracts protect against sperm damage in mice under bisphenol A induced reproductive damage.Echinacoside(ECH) is one of the major active components.The present study investigated the mechanisms behind the possible protective effects of ECH against oligoasthenospermia in rat and identified the interaction between ECH and AR.METH.ODS The distribution of ECH was assayed by HPLC,the quantity and quality of sperm was evaluated and hormone levels were determined by radioimmunosorbent assay.The levels of androgen receptor(AR) and key steroidogenic-related genes were reduced as determined by Western blotting and qPCR analysis.The interaction between ECH and AR were evaluated by fluorescence localization assay,indirect ELISA and molecular docking.RESULTS ECH significantly increased the quantity of sperm and secretions of luteinizing hormone and testosterone.ECH was distributed to the hypothalamus but not in the testes.ECH combined with hypothalamic AR in the pocket of Met-894 and Val-713 to inhibit transfer of AR from the cytoplasm to nuclei in the hypothalamus.While negative feedback of sex hormone regula.tion was inhibited,positive feedback was stimulated to increase the secretion of luteinizing hormone and testosterone subsequently enhancing the quantity of sperm.C.militaris significantly alleviated the BPA-induced reproductive damage by increasing testicular superoxide dismutase(SOD),glutathione peroxidase(GSH-PX) and glutathione(GSH);as well as by reducing serum malondialdehyde(MDA).C.militaris not only obviously enhanced the levels of serumLH and T,but it also improved the sperm count and motility compared to the BPA-treated group.CONCLUSION C.militaris and ECH protect the BPA induced reproductive damage.ECH blocks AR activity in the hypothalamus to increase the quantity of sperm and protect against oligoasthenospermia in rats.

比卡鲁胺抑制CWR22Rv1细胞移植裸鼠前列腺癌的机制研究

目的:探讨比卡鲁胺抗CWR22Rv1细胞移植裸鼠前列腺癌的作用机制。方法:采用瘤块接种的方法制作裸小鼠前列腺癌模型,观察比卡鲁胺治疗后的移植瘤重量和体积,并计算抑瘤率,收集移植瘤标本,使用光镜观察法、免疫组化法、基因芯片法和实时定量RT-PCR法比较比卡鲁胺组和阴性对照组肿瘤相关指标的差异。结果:①比卡鲁胺低、中、高剂量组抑瘤率分别为10.77%、37.32%和63.28%(P<0.01)。②光镜观察:对照组肿瘤内癌细胞生长旺盛,移植癌细胞保持原有异型性。而比卡鲁胺低、中和高剂量组呈腺癌典型表现,癌细胞出现不同程度的退变。③免疫组化:低、中、高剂量组增殖细胞核抗原增殖指数同阴性对照组相比明显减小(P<0.01)。对照组每200个细胞中平均有180±8个细胞雄激素受体(androgen receptor,AR)呈阳性表达,而高剂量组中AR阳性细胞数较对照组明显减少(P<0.01)。④基因芯片:高剂量组在前列腺癌相关基因表达丰度上明显低于对照组,主要为AR和关联蛋白、细胞黏附分子和细胞周期相关基因,并且实时定量RT-PCR结果与基因芯片结果基本一致。结论:比卡鲁胺抗22Rv1细胞移植裸鼠前列腺癌效果显著,主要通过降低细胞核AR表达、减少细胞黏附、调控细胞周期和抑制细胞增殖等发挥作用。

老年前列腺增生症各区细胞雌雄激素受体表达的意义

目的 探讨前列腺增生症 (BPH)各区细胞雌激素受体表达的意义。方法 采用免疫流式细胞术对 3 3例患者前列腺周边区 (PZ)、移行区 (TZ)和中央区 (CZ)细胞的雌雄激素受体的阳性表达率的强度进行分析。结果 TZ细胞雌激素受体 (ER )的阳性率和表达量明显高于PZ和CZ(P <0 .0 5和 0 .0 1)。而TZ细胞雄激素受体 (AR)的阳性率明显低于PZ细胞 ,TZ细胞AR的表达量也比另两个区低 (P <0 .0 1和 0 .0 1)。结论 TZ细胞ER的高表达可能是BPH发病的重要因素。