EGCG调控miR-344a/484抗良性前列腺增生的作用和机制研究

良性前列腺增生（BPH）发病率逐年升高,其引起的下尿路症状（LUTS）严重影响患者的生活质量。研究表明腺体增生和纤维化是BPH导致LUTS的关键之一，而HIF-1α是BPH缺氧微环境刺激腺体增生和纤维化的核心节点。我们通过高通量测序发现BPH病程中存在miR-344a/484水平降低的现象。细胞预实验提示miR-344a/484与HIF-1α表达呈负相关。同时我们证实表没食子儿茶素没食子酸酯（EGCG）能改善大鼠BPH，上调miR-344a/484。因此提出miR-344a/484调控HIF-1α表达而改善BPH病程的腺体增生和纤维化，EGCG的抗BPH效应与上调miR-344a/484有关。并拟在不同层面通过上调或抑制miR-344a/484、基因沉默或慢病毒转染过表达HIF-1α及引入HIF-1α高表达转基因小鼠予以证实，有望为BPH的治疗提供新的策略。

The incidence of benign prostate hyperplasia (BPH) increases year by year. Lower urinary tract symptoms (LUTS) caused by BPH seriously affect the life quality of patients. Studies show that glandular hyperplasia and fibrosis are the key factors for LUTS caused by BPH. And HIF-1α is a core node in the process of glandular hyperplasia and fibrosis under the prostatic hypoxia microenvironment in BPH. We found that the prostatic levels of miR-344a/484 were decreased in BPH via high throughput sequencing. Moreover, cellular preliminary experiment indicated that there was a negative correlation between the levels of miR-344a/484 and HIF-1α. We also confirmed that epigallocatechin-3-gallate (EGCG) could ameliorate BPH and increase the prostatic levels of miR-344a/484 in rats. Therefore, we propose that miR-344a/484 improve the glandular hyperplasia and fibrosis in BPH via inhibiting the expression of HIF-1α, and EGCG attenuates BPH through up-regulating miR-344a/484. The aim of this project is to confirm these hypotheses via up-regulating or down-regulating miR-344a/484, silencing or lentivirus transfection over-expressing HIF-1α, and introducing HIF-1α high expression transgenic mice. It is expected to provide a new strategy for the treatment of BPH.