IL-6调控慢性非细菌性前列腺炎自噬的作用机制研究

It has been reported that the IL-6, a cytokine, plays a significant role in the chronic nonbacterial prostatitits (CNP), but its details of mechanism have been poorly understood. Certain studies also show the autophagy has an important effect on the inflammation, and its mechanism may be IL-6/STAT3 pathway and NLRP3 inflammasome. We have illustrated IL-6 may regulate autophagic pathway among CNP, among which the STAT3 pathway and NLRP3 inflammasome may play certain roles. This research aims to study the correlation of the IL-6 and autophagic pathway, STAT3 pathway, NLRP3 inflammasome; explore how IL-6 regulates STAT3 pathway and NLRP3 inflammasome regulates IL-6/STAT3 pathway; explain the mechanism regarding IL-6 effect on autophagy and demonstrate the key molecule and pathway. These results may reveal the seminal CNP’s pathogenesis, and provide the novel strategies for CNP’s treatment and prevention.

研究表明，细胞因子IL-6在慢性非细菌性前列腺炎（CNP）的发生、发展过程中起着重要的作用，但该细胞因子调控CNP的具体机制仍不十分清楚。同时相关研究表明，细胞自噬参与调控炎症的发生、发展；其可能机制是通过IL-6/STAT3信号通路及NLRP3炎症体。我们的前期研究结果表明IL-6可能参与调控CNP中自噬信号通路，因此IL-6调控CNP中自噬通路的机制是可能是通过STAT3信号通路和NLRP3炎症体。本项目拟在建立大鼠CNP模型的基础上，研究CNP中IL-6调控自噬通路、STAT3通路、NLRP3炎症体的相关作用；进一步研究CNP中IL-6对STAT3 信号通路调控、NLRP3炎症体对IL-6/STAT3信号通路的调控，阐明IL-6调控CNP中自噬通路的相关机制；发现其关键的调控位点和相关信号通路。对CNP发病机制提供新的理论依据，为CNP治疗及预防提供新的思路、新的作用靶点。

细胞因子IL-6在慢性非细菌性前列腺炎（CNP）的发生、发展过程中起着重要的作用。本课题采用相关分子生物学实验方法，检测CNP组与对照组中自噬相关蛋白分子、自噬体以及STAT3通路蛋白、NLRP3炎症体的表达情况，探讨STAT3通路和NLRP3炎症体在CNP中IL-6调控调控自噬的作用机制；检测三氧化二砷联合Rad001通过诱导细胞自噬协同抗前列腺癌的体内、体外状态生物学效应。研究结果发现，加入IL-6抑制剂后可以减轻大鼠前列腺组织中CNP的形成；大鼠CNP组与对照组相比自噬相关分子Beclin1，炎症相关分子STAT3、NLRP3的表达明显增加；抑制IL-6可以降低CNP中自噬过程中自噬小体的表达；同时抑制CNP中IL-6可以上调炎症相关分子STAT3表达。三氧化二砷联合Rad001具有协同抗前列腺癌生物学效应。