IL-17A通过内质网应激途径促进巨噬细胞活化在脑出血炎症损伤的正反馈调节机制研究

我们前期研究证实脑出血代谢产物促进TH17/IL-17A表达上调，并诱导巨噬细胞内质网应激和炎症反应，加重脑出血损伤，但具体机制尚不清楚。我们还发现IL-17A通过脂质伴侣aP2促进内质网应激程度和巨噬细胞炎症反应。结合相关研究基础，我们推测IL-17A激活巨噬细胞NF-κB和MAPK信号通路，并通过NF-κB和ERK，p38通路上调脂质伴侣aP2的表达，进一步活化p-eIF2α和XBP1s，激活内质网应激反应，从而促进巨噬细胞介导的脑出血炎症损伤。本实验拟在脑出血模型上，运用WB、共聚焦及FACS等技术，通过调控IL-17A和aP2的水平，检测对巨噬细胞内质网应激及炎症的影响。本研究将从全新的角度和思路阐明IL-17A通过内质网应激参与“巨噬细胞-TH17”之间的正反馈调节，深入探讨“IL-17A-内质网应激-巨噬细胞炎症”的调控模式，并为脑出血的治疗提供新思路。

Our previous studies have confirmed that intracerebral hemorrhage can promote the expression of TH17/IL-17A , induce macrophage endoplasmic reticulum stress and inflammatory response, which may aggravate the damage of intracerebral hemorrhage. However, the specific mechanism is not clear. We also found that IL-17A promoted endoplasmic reticulum stress and inflammatory response of macrophage through lipid chaperone aP2. On the basis of relative studies, we hypothesize that IL-17A activates NF-κB and MAPK signal pathway in macrophage and upregulates the expression of lipid chaperone aP2 through NF-κB, ERK and p38 pathway, furtherly activate p-eIF2α and XBP1s to promote endoplasmic reticulum stress, thereby promoting macrophage-mediated inflammatory injury of intracerebral hemorrhage. In this experiment, we investigate the effects IL-17A and aP2 on macrophages endoplasmic reticulum stress and inflammation by WB, confocal and FACS in intracerebral hemorrhage model. This study will elucidate the positive feedback regulation between IL-17A and aP2, and explore the relationship "IL-17A - endoplasmic reticulum stress - macrophage inflammatory regulation" model, and provide new ideas for the treatment of intracerebral hemorrhage.