从HSP70对NF-κB信号转导通路的调控探讨炎调方治疗脓毒症急性肺损伤的作用机制

Purging bowel and activating blood, clearing Ying system and removing heat from blood and detoxifying method is one of the treatments of sepsis-induced acute lung injury with Traditional Chinese Medicine. Yantiaofang is based on this method theory and the clinical researches proved that Yantiaofang treats sepsis-induced acute lung injury effectively and it reduced patients' serum proinfammatory cytokines levels. Animal studies also indicated that Yantiaofang could increase lung HSP70 gene and protein expressions, could control NF-κB activity and reduced serum proinflammatory factors level. Basing on previous researches, the contents of this research are follows: ①the mechanism of Yantiaofang treating sepsis-induced acute lung injury by HSP70 through TRLs/NF-κB pathway; ②the mechanism of Yantiaofang treating sepsis-induced acute lung injury by HSP70 through p38 MAPK/NF-κB pathway and, we hope to explore the mechanism of Yantiaofang treating sepsis-induced acute lung injury through arising HSP70 expression to modulate NF-κB signal transduction pathway which would provide the scientific clues on Traditional Chinese Medicine treating sepsis-induced acute lung injury.

通腑活血、凉营解毒是中医药治疗脓毒症急性肺损伤的治法之一。前期临床研究发现基于此治法制定的炎调方治疗脓毒症急性肺损伤疗效确切，并能降低患者外周血促炎症细胞因子水平；同时动物实验提示炎调方能上调肺组织HSP70基因和蛋白表达，能抑制NF-κB活性，降低血清促炎症细胞因子水平。本课题在前期临床及实验研究的基础上，拟以HSP70为切入点开展①炎调方对TLRs/NF-κB信号转导通路的调控作用；②炎调方对p38 MAPK/NF-κB信号转导通路的调控作用研究；力图探索炎调方上调HSP70表达，调控NF-κB信号转导通路的作用途径，从而为中医药治疗脓毒症急性肺损伤提供进一步的实验研究线索。

通腑活血、凉营解毒是中医药治疗脓毒症急性肺损伤的治法之一，前期临床研究发现基于此治法制定的炎调方治疗脓毒症急性肺损伤疗效确切。本研究选用地塞米松作为药物对照组，比较不同组别脓毒症大鼠肺损伤情况，检测血清或肺组织HSP70、NF-κB等指标,发现炎调方与地塞米松相似，能有效减轻脓毒症急性肺损伤大鼠的炎症反应，验证了其对脓毒症急性肺损伤具有保护作用。在此基础上以HSP70为切入点进一步探索炎调方对NF-κB信号转导通路的调控作用，发现炎调方能上调HSP70，抑制TLRs和p38MAPK信号转导，稳定IκB蛋白空间，抑制NF-κB 活性，抑制促炎症细胞因子TNF-α、IL-1β、IL-6、IL-8的释放，为中医药治疗脓毒症急性肺损伤提供了进一步的实验研究线索。