酒精介导自噬调控慢性非细菌性前列腺炎Th17/Treg失衡作用及机制研究

Chronic nonbacterial prostatitis(CNP) has become a common disease in young man, it has a significant morbidity, low cure rate and easy recurrence, and severely threatens male health and life quality, but the mechnaism of CNP remains unknown.Alcohol could exacerbate clinical symptoms of CNP, the mechnaism remains unknown. Some studies indicate that alcohol could affect autophagy process, which is a key to maintain the homeostasis of immune and inflammation in human body. In addition, researchs found that alcohol and autophagy could regulate the functions of Th17 cells and Treg cells. Our previous studies have concluded that the imbalance functions of Th17 / Treg had an important role in the development of CNP, indicating alcohol may promote CNP through autophagy and influence the balance of Th17 / Treg cells. In this research, we intends to study the alcohol and T lymphocyte subsets cells, applying the animal models of CNP, exploring the role of Th17 / Treg imbalance in the pathogenesis of CNP, investigating the mechanisms of alcohol on Th17 / Treg imbalances in CNP development, detecting mechnaisms alcohol mediate autophagy regulate the function imbalance of T lymphocyte subsets cells in CNP, revealing its mechanisms of the key molecular and regulatory net, it provide the new theoretical basis of mechanisms in CNP, and provide the new strategies in CNP

慢性非细菌性前列腺炎(CNP)是好发于男性青壮年的常见病，该病患病率高，治愈率低，且易复发，严重危害患者身心健康，发病机制尚不明确。在临床实践中，我们发现酒精促进CNP的发生发展，同时酒精也调控自噬相关过程，自噬是机体免疫和炎症的关键调控中枢。此外研究还发现酒精和自噬相关通路调控T淋巴细胞亚群Th17/Treg功能。本课题组前期研究发现Th17/Treg功能失衡在CNP的发病中起关键性作用，推测酒精调控CNP发病的机制是通过自噬介导T淋巴细胞亚群Th17/Treg功能失衡的。本项目拟借助CNP鼠模型，探讨Th17/Treg失衡在CNP发病中的作用；研究酒精对CNP中Th17/Treg失衡的调控作用；揭示酒精介导自噬信号途径对CNP中Th17/Treg调控机制；进而阐释酒精诱导CNP的发病机制的调控网络组成和关键调控位点。有望为酒精诱导CNP发生机制提供新的理论依据，为CNP防治提供新靶点

慢性非细菌性前列腺炎(CNP)是好发于男性青壮年的常见病，该病患病率高，治愈率低， 且易复发，严重危害患者身心健康。流行病学研究显示，酒精与慢性非细菌性前列腺炎的症状密切相关。在临床实践中，我们发现，饮酒患者会有较为严重的慢性前列腺炎症状，但具体机制不清。本研究从动物水平探索了酒精作用于CNP的可能机制。首先，课题组通过建立慢性前列腺炎动物模型（EAP），在动物水平上发现Th1、Th17在CNP发病过程中显著增加及Th1/Th2、Th17/Treg比例的失衡，酒精可通过激活NLRP3炎症小体通路加重EAP小鼠慢性前列腺炎症，而不是直接诱导引起前列腺炎。我们还发现肠道菌群失调参与EAP诱导的抑郁行为，并可能通过肠脑轴途径增加海马小胶质细胞和星型胶质细胞的激活，促进TNF-α、IL-1β等炎症因子的释放，形成神经炎症，进一步介导谷氨酸和五羟色胺神经递质系统异常，导致抑郁的发生。此外，我们还发现褪黑素可通过抑制NLRP3炎症小体的激活从而缓解EAP小鼠慢性前列腺炎症；HA合成酶抑制剂（4-MU）可通过抑制Th1的分化缓解EAP小鼠慢性前列腺炎症；毛萼乙素可通过影响NF-κB 通路缓解EAP小鼠慢性前列腺炎症。本研究初步阐明了酒精对于慢性前列腺炎的作用及其分子机制，为慢性前列腺炎的诊治提供了一种新的思路和可能的治疗靶点。