基于TNF-α/CTRP9/p42/44MAPK信号通路探讨当归红芪超滤物干预重离子束致心肌细胞损伤的氧化应激机制

Radiation-induced heart disease（RIHD）has been endangering human health seriously. Reent research indicated that the pathogenesis of radiogenic myocardial damage was associated with oxidative stress, directly or indirectly induced myocardial cell apoptosis and fibrosis. In the previous study we detected that Ultra-filtration Extract Mixture from Angelica Sinensis and Hedysarum Polybotrys played an important role in myocardial protection due to enhance the ability of anti-oxidative damage from myocardial cells. In addition,it inhibited cardiac fibroblasts proliferation, collagen accumulation and pathological lesion induced by X-ray or heavy ion beam, promoted the expression of hsp70 expression, inhibited the expression of caspase-3, affected the mitochondrial membrane potential concentration of intracellular calcium. No reports at home and abroad conclude the relationship between CTRP9 and p42/44MAPK, and the regulatory mechanism of the inflammatory cytokine TNF-α on expression of CTRP9. The research will focus on the mechanism of TNF-α/CTRP9/p42/44 MAPK signaling pathway involved in myocardial oxidative stress, and the specific protection mechanism of Ultra-filtration Extract Mixture from Angelica Sinensis and Hedysarum Polybotrys through TNF-α/CTRP9/P42/44 MAPK signaling pathway in vitro experiment using gene silencing and gene transfection techniques. This research subject will provide new targets or prevention and treatment of radiogenic myocardial damage, and establish a theoretical basis for clinical application of Ultra-filtration Extract Mixture from Angelica Sinensis and Hedysarum Polybotrys, which has a important theoretical significance and application value

放射性心脏疾病（RIHD）严重威胁人类身心健康。 现代研究表明RIHD的发病机理与氧化应激性密切相关，氧化应激可直接或间接诱导心肌细胞凋亡和纤维化。课题组前期研究发现具有益气生血功效的当归红芪超滤物可通过抗氧化作用、促进hsp70表达、抑制caspase-3表达、影响心肌胞浆钙离子流动和线粒体膜电位保护心肌细胞，对重离子束或x线诱导的心肌成纤维细胞增殖和胶原的积累及病理损伤有抑制作用。研究结果表明心肌细胞损伤时TNF-α、CTRP9 、p42/44表达异常，但干预CTRP9/p42/44 MAPK在RIHD时的关联，以及炎症因子TNF-α对CTRP9的调控机制，尚无报道。本课题拟从细胞及在体水平，用基因沉默、转染等技术探讨TNF-α/CTRP9/p42/44 MAPK通路在RIHD过程中的作用，以及当归红芪超滤物通过该信号通路发挥心肌保护作用的具体机制。

放射性心脏疾病（RIHD）严重威胁人类身心健康。 现代研究表明RIHD的发病机理与氧化应激性密切相关，氧化应激可直接或间接诱导心肌细胞凋亡和纤维化。课题组研究发现具有益气生血功效的当归红芪超滤物可通过抗氧化作用、促进hsp70表达、抑制caspase-3表达、影响心肌胞浆钙离子流动和线粒体膜电位保护心肌细胞，对重离子束或x线诱导的心肌成纤维细胞增殖和胶原的积累及病理损伤有抑制作用。项目组证实X线辐射诱导氧化应激是心肌损伤的关键病理过程，而且氧化应激反应通过TNF-α/CRTP9/p42/44 MAPK信号通路介导了心肌细胞凋亡，最终导致了心肌纤维化的发生是RIHD发生、发展的关键机制。研究结果进一步丰富了RIHD的发病机制，为RIHD的防治提供了基础。项目组还证实了当归红芪超滤物具有抑制氧化应激反应及减轻心肌纤维化的作用，其机制与抑制TNF-α/CRTP9/p42/44 MAPK信号通路介导的心肌细胞凋亡有关。