线粒体自噬PRDX3-LC3/NIX信号通路在前列腺增生的调控机制研究

年龄（衰老）是前列腺增生（BPH）发病的特征因素，增生上皮细胞已被证实自噬功能减退。我们研究表明 MAPS1-LC3/NIX 复合物可促进自噬 (Liu LY,2010 Cancer Research, 2012 Autophagy)；及miR-23b调控线粒体蛋白PRDX3 参与氧化应激保护（He HC,2012，FEBS Letter）。但BPH中自噬功能减退是否也与线粒体PRDX3因子氧化应激功能相关？我们发现 PRDX3可以促进线粒体自噬功能，为此，我们首次提出"线粒体PRDX3-自噬LC3/NIX信号通路"调控前列腺增生的衰老过程。通过已构建的PRDX3载体与原代增生细胞，获得 PRDX3参与线粒体自噬的直接证据，进一步利用老年大鼠增生模型，分析基因、蛋白表达谱，阐明前列腺增生自噬调控的机制，建立衰老-自噬-增生的模型网络，为前列腺增生新的治疗方案提供可靠的科学依据。

BPH is one of the most common diseases in the old men and age plays an important role in the initiation of BPH. Interestingly, autophagy dysfunction can be found in prostatic hyperplasia. At present, we have testified the MAPS1-LC3/NIX could promote autophagy and streng then DNA stability as a complex (Liu LY,2010 Cancer Research, 2012 Autophagy). In addition, we found that miR-23b control PRDX3 which is a kind of mitochondrial protein to involve in oxidative stress protection（He HC,2012，FEBS Letter）. According to it , we wonder if the autophagy dysfunction happened in prostatic hyperplasia is related with mitochondrial oxidative stress function. We found that autophagy activity is increased more significantly in the over-expressed PRDX3 BPH-1 cell line than in the normal BPH-1 cell line. Therefore, we first propose the mitochondrial PRDX3-autophagy-LC3/NIX signal pathway involve in the prostatic hyperplasia aging process. We try to prove PRDX3 get involved in the mitochondrial autophagy by using original clinical cell line and prostatic hyperplasia elder mice model, illustrating if"stress response- mitochondrial autophagy-hyperplasia" existing in the aging process. Through analyzing gene expression and protein expression spectrum, we try to confirm the gene involving in the aging autophagy regulation and set up aging-autophagy-hyperplasia functional network, providing more scientific evidence and new therapeutic regimen forBPH prevention.