髓核细胞“免疫应答”痤疮丙酸杆菌并经“效应产物”IL-8诱导椎间盘退变的机制研究

As an important opportunistic pathogen, P.acnes not only leads to severe discitis, but also results in latent infection in degenerated intervertebral discs. In our previous study, the wild-type strain of P.acnes was firstly isolated from degenerated intervertebral discs in Han population and the histological evidence of the bacterium was acquired firstly at the same time. More importantly, P.acnes has been proved to be the pathogen responsible for disc degeneration according to our previous study in vivo and in vitro..However, until now, there is still no pathophysiologic mechanism to explain why and how P.acnes induces disc degeneration. Based on the results of our preliminary study, we hypothesize that nucleus pulposus cells play vital roles in the process that P.acnes induces disc degeneration. Specifically, nucleus pulposus cells are supposed to act like immunocytes. They would immunologically react with P.acnes based on the cell signal pathway of TLR-2/MyD88/NF-kB and secrete IL-8. Then, the IL-8 will result in disc degeneration directly. .Overall, the project tries to figure out how P.acnes induces disc degeneration, which will be definitely useful for alternative therapy for P.acnes-induced disc diseases in clinical.

痤疮丙酸杆菌(P.acnes)是一类重要的机会性致病菌，其能在椎间盘内潜伏定植并诱导椎间盘退变。既往研究中，本课题组已在国人退变椎间盘内首次分离培养出P.acnes并获取了该菌定植的组织学证据，且从多个角度论证了该菌与椎间盘退变的关联性。基于初期研究结果，本研究拟进一步提出该菌诱导椎间盘退变的机制假设，即：椎间盘髓核细胞扮演了部分免疫细胞的角色，经免疫相关信号通路TLR-2/MyD88/NF-kB “识别”潜伏定植的P.acnes后，“应答”分泌了效应产物白细胞介素-8(IL-8)，并经IL-8直接诱导了椎间盘退变。本研究立足于P.acnes椎间盘内潜伏定植这一重要临床问题，系统回答了髓核细胞的“免疫应答”作用在P.acnes诱导的椎间盘退变中的作用，验证了清除IL-8在缓解P.acnes诱导的椎间盘退变中的有效性，为理解和治疗P.acnes诱导的椎间盘疾病提供了全新的理论依据。

痤疮丙酸杆菌(P.acnes)是一类重要的机会性致病菌，其能在椎间盘内潜伏定植并诱导椎间盘退变。既往研究中，本课题组已在国人退变椎间盘内首次分离培养出P.acnes并获取了该菌定植的组织学证据，且从多个角度论证了该菌与椎间盘退变及腰痛的关联性。在本研究中，我们进一步论证了该菌在椎间盘退变相关性盘源性腰痛中的病理作用，证明了椎间盘髓核细胞扮演了部分免疫细胞的角色，通过细胞表面TLR-2受体（Toll-like receptor-2）识别了P.acnes，而后通过下游的NF-kB转录因子调控了“免疫效应”产物白细胞介素-8(IL-8)的合成和分泌，并由IL-8诱导了椎间盘退变相关盘源性腰痛。本研究立足于P.acnes椎间盘内潜伏定植这一重要临床问题，系统性回答了P.acnes诱导椎间盘退变相关性盘源性腰痛的病理和病理生理机制，阐述了髓核细胞对细菌“免疫应答”在椎间盘疾病中的作用，验证了IL-8在P.acnes诱导椎间盘退变相关性盘源性腰痛中的病理学作用，为理解和治疗P.acnes诱导的椎间盘退变疾病提供了全新的理论依据。