HMGB1通过TLR4受体调节IL-23/IL-17轴在心肌缺血再灌注损伤中的作用及机制研究

Myocardial ischemia-reperfusion(I/R) injury refers to myocardial tissue injury must be worsened after restoring the blood supply on the ischemia myocardium, and its mechanism is very complicated. Although previous studies showed that HMGB1 and IL-17 play an important role in myocardial ischemia-reperfusion injury, the relevent molecular mechanism is unclear. In this study, we will constructe the TLR4-deficient mice (C3H/HeJ) and controls (C3H/HeN) model of myocardial I/R injury and the mice will be subjected to 30 min ischemia and 2h reperfusion. And we will use molecular biology techniques including elisa, westernblot, real-time pcr, immunohistochemistry etc, to explore the relationship and relevant molecular mechinesms between HMGB1 and the IL-23/IL-17 axis in myocardial I/R injury. Our findings may clarify this association is due to HMGB1 binding to its TLR4 receptor, causing the activation of NF-κB, amplifying the inflammatory response, boosting macrophages secreting IL-23, causing the immune response, stimulating IL-23/IL-17 axis play a crucial role in myocardial ischemia-reperfusion injury via causing inflammatory reaction, apoptosis and mediating neutrophils infiltration. And this study may provide reference value for the prevention and treatment of myocardial I/R injury.

心肌缺血再灌注损伤是指心肌缺血基础上恢复血供后心肌组织损伤反而加重的现象，其机制十分复杂。目前研究发现HMGB1与IL-17在心肌缺血再灌注损伤中发挥重要作用，但其有关分子机制尚不清楚。本研究以TLR4-基因缺陷型 (C3H/HeJ) 小鼠和对照组小鼠(C3H/HeN)为对象，构建缺血30min及再灌注2h的在体心肌缺血再灌注模型，采用elisa、western blot、real-time pcr、免疫组化等分子生物学技术，探讨HMGB1参与心肌缺血再灌注损伤是否与IL-23/IL-17轴有关及可能的分子机制。通过本研究将可能阐明这种关联是由于HMGB1与TLR4受体结合，引起NF-κB活化，放大炎性效应，促进吞噬细胞分泌IL-23，产生免疫应答，刺激IL-23/IL-17轴在心肌缺血再灌注损伤中的炎性反应、细胞凋亡和中性粒细胞浸润发挥重要作用。从而为临床防治心肌缺血再灌注损伤提供参考。