雄激素-雄激素受体通路是良性前列腺增生发生发展的关键。抑制雄激素生成是已发现的抗前列腺增生靶点，推测促进雄激素代谢为另一靶点。Naftopidil是治疗良性前列腺增生的一线用药，其改善下尿路症状的作用机理已经明确，而抑制前列腺细胞增殖作用机制尚未明确。我们的研究发现，naftopidil与活性雄激素均主要由UGT2B7代谢，且naftopidil对UGT2B7活性有对映体选择性激动作用。推断naftopidil可能通过上调UGT2B7，促进雄激素代谢发挥抗前列腺增生作用，且存在优势异构体。本项目拟从药物对内源性物质代谢的相互作用入手，明确naftopidil对映体对体内外雄激素代谢的影响，并研究NAF对映体对UGT2B7及其转录因子Nrf2、CAR和FXR的调节作用，阐明NAF对映体抗良性前列腺增新靶点，明确该作用中的优势异构体。为新靶点的发现和优势异构体的开发提供依据。

Androgen-androgen receptor signals play vital roles in the initiation and progression of benign prostate hyperplasia (BPH). Inhibiting the production of androgen was proved to be an effective target. It is speculated that promoting androgen elimination may be another possible target. Naftopidil, a α1D-adrenoceptor blocker, is utilized extensively for lower urinary tract symptoms (LUTS) caused by BPH. However，the mechanism for inhibiting prostate cell proliferation has not been clarified. Our previous study had revealed that UDP- Glucoronosyltransferase (UGT) 2B7 is the principal enzyme responsible for naftopidil enantiomer metabolism. Interestingly, UGT2B7 also catalyze androgen to form inactive metabolize in vivo and vitro. Our study also found that naftopidil enantioselectively induces UGT2B7 in vitro. Consequently, we speculate that naftopidil could enantioselectively promote the metabolism of androgen, then inhibit prostate hyperplasia. Based on the point of drugs metabolic interaction, the present study will study the mechanism which naftopidil regulate the activity and expression of UGT2B7 and transcription factor Nrf2, CAR, FXR and investigate the influence on androgen metabolism. This study will indicate a new mechanism inhibiting BPH of naftopidil and a superior enantiomer. These results may contribute valuable information for new targets discovery and clinical rational medication.