前列腺增生症（BPH）随着我国人口老龄化和生活水平的提高，发病率逐年上升，引起了广泛的关注。BPH属于中医学"癃闭"的范畴，历代医家对其进行了深入的病证研究，创制了许多行之有效的治法方药，但其病因病机尚未完全阐明。课题组前期研究发现肾虚血瘀为BPH的基本病机，并成功建立了BPH肾虚血瘀证大鼠模型，进而初步发现补肾活血结合抗炎抗氧化方能调节大鼠性激素水平、影响前列腺增生相关蛋白及相关细胞因子，从而起到抑制前列腺增生的作用。已有研究证实ROS、SOD、HO-1等与BPH相关，而COX-2/Nrf2信号通路能调控这些因素。本研究基于此信号通路，结合分子生物学和基因敲除技术，与代谢组学技术相结合，从信号转导和基因调控的角度探讨肾虚血瘀结合抗炎抗氧化防治前列腺增生的作用和机理，寻找药物作用的分子靶标，深入阐述BPH病因病机，探寻新的BPH防治方法，同时为相关方剂的开发和应用提供依据。

With the growth in the living standard and population aging problem in our country, the incidence of Benign Prostate Hyperplasia(BPH) raised wide public concern. BPH belongs to the category of "Longbi (retention of urine)" in traditional Chinese medicine. Many medical scientists had done in-depth studys of its symptom and created a lot of effective treatment method. However, its etiology and pathogenesis has not been fully understood.The research group found that kidney deficiency and blood stasis was the basic pathogenesis of BPH and successfully established the BPH kidney deficiency and blood stasis rat model. Then it has been found preliminary that the Bushen Huoxue (tonifying kidney and activating blood) combining with anti-inflammatory antioxidant prescription can control rats sex hormone level and influence prostatic hyperplasia related protein and cell factors to inhibit the prostatic hyperplasia.This study based on the signaling pathway, combining with molecular biologies, gene knockout technologies and metabolomics technologies, discusses the role and mechanism of Bushen Huoxue combining with anti-inflammatory antioxidation in preventing prostatic hyperplasia from the signal transduction and gene regulation perspectives. Our research aim to analyse the cause and pathogenesis of BPH, search new prevention and cure methods for BPH, and provide the basis for the development and application of related Chinese medicinal formulae.

前列腺增生症是中老年男性的常见病和多发病，许多中老年男性倍受前列腺亚健康的困扰。因此，发挥中医药的疗效优势，采用中西医结合防治前列腺增生是目前研究的热点。课题组结合文献和前期研究，提出假设：补肾活血法结合抗炎抗氧化组方即克癃方可能通过激活COX-2/Nrf2信号通路，触发抗炎抗氧化机制，结合中医补肾活血的功效，达到预防和治疗前列腺增生的目的。本课题围绕重点问题进行了探索，选用PC-3细胞和SD雄性大鼠进行体内外实验。首先利用H2O2诱导PC-3细胞形成氧化应激模型，证实了克癃方干预后细胞内ROS 含量降低，GSH 的水平升高，细胞内氧化应激环境得到改善。进一步研究发现，克癃方不能明显降低抗炎因COX-2的蛋白和mRNA的表达，但显著诱导了Nrf2及其下游抗氧化基因HO-1、NQO1、GST等的表达。又从动物水平进行了考察，通过观察大鼠的舌象、粪便、精神状况等确定了具有肾虚血瘀征象的前列腺增生模型的建立。高剂量的克癃方可显著降低前列腺指数，改善病理组织形态。同时，低剂量的克癃方可诱导Nrf2和NQO1的蛋白表达。在此基础上，建立前列腺增生大鼠模型考察克癃方的疗效及抗氧化机制。证实高剂量的克癃方能降低性激素含量，改善前列腺的病组结构，促进血清中GSH的含量增加。而低剂量的克癃方能诱导Nrf2及下游抗氧化基因Nrf2、HO-1和NQO1的表达。通过一系列分子生物学研究，从信号通路的角度证实了克癃方具有抗氧化活性。本研究融合了中医理论，确证了克癃方的疗效，为治疗前列腺增生的新药开发提供了新的理论依据。