基于α7nAChR介导的NF-κB和JAK2/STAT3信号通路的针刺干预干眼炎症的作用机制研究

干眼是临床上常见眼表疾病，常伴有局部炎症，临床证实针刺有效治疗干眼炎症，本课题组前期工作发现针刺可调节胆碱能通路减轻干眼炎症。本项目将进一步探讨针刺调节α7nAChR及其介导的NF-κB和JAK2/STAT信号通路，抑制炎症的效应及机制。采用临床有效穴位对干眼模型兔进行针刺治疗，从分子及蛋白水平各有侧重分析针刺对泪腺、角膜及结膜组织ACh、α7nAChR水平；胆碱能抗炎通路关键基因及蛋白如NF-κB、JAK2、STAT3的表达；组织及泪液中相关细胞炎症因子IL-1、IL-6 和TNF-α等的变化。并用α7nAChR拮抗剂阻断胆碱能抗炎通路，阐述针刺调节干眼炎症模型兔中α7nAChR及其介导的信号转导通路NF-κB和JAK2/STAT3表达，抑制炎症因子释放，从而减轻眼表炎症的机制。该工作将明确针刺调控胆碱能抗炎通路干预干眼炎症的作用机制。有望通过该项研究对针刺治疗干眼炎症的机制产生突破性进

Dry eye is a common ocular surface disease, often accompanied by local inflammation. Clinical practice have proved that acupuncture effectively treat dry eye with inflammation. Our previous study found that acupuncture could regulate the cholinergic pathway and alleviate dry eye with inflammation. This project will further explore the effects and mechanisms of acupuncture on α7nAChR and its mediated NF-κB and JAK2/STAT3 signaling pathways and inflammation. The rabbit models of dry eye were treated with acupuncture according to the effective acupoint in clinical treatment, and then analysis the contents of ACh and α7nAChR in lacrimal gland, cornea and conjunctiva; assess expression of NF-κB, JAK2, STAT3 genes and proteins which are associated with cholinergic anti-inflammatory pathways at the molecular and protein levels, respectively. Moreover, this project will explore the change of the related-inflammatory factors IL - 1, IL-6,TNF-α and so on in tissues and tears. More importantly, this project will clarify the effect and mechanism of acupuncture on the change of NF-κB, JAK2 and STAT3 of the main signal transduction pathways mediated by α7nAChR in rabbits with dry eye, subsequently to inhibit the release of inflammatory cytokines, and reduce the ocular surface inflammation using α7nAChR antagonist to block the cholinergic anti-inflammatory pathway. This project will explicit the effect and mechanism of acupuncture on the regulation of ocular inflammation by cholinergic anti-inflammatory pathway. It is hoped that this study will make a breakthrough in the mechanism of acupuncture for dry eye inflammation.