丹参酮ⅡA保护放射性心脏损伤的作用及其机制研究

Radiation-induced heart damage（RIHD）has been the important clinical complication of radiotherapy in cancer and the negatively influence the efficacy of radiotherapy and the quality of life. Our previous studies showed that tanshinoneⅡA protect myocardial cells through p38MAPK signaling pathway in radiotherapy, but the molecular mechanism of the tanshinone ⅡA mediated regulation of p38MAPK is still unknown. In current study, we will establish the radioactive heart damage models by using primary myocardial cell and mouse exposed to X-ray. the molecular mechanism of the protection of tanshinone ⅡA in mouse from radiation damage will be studied by detecting MALAT1 expression and p38MAPK signaling pathway. The relationship between the MALAT1 and p38MAPK through genetic intervention will be studied, which will reveal the molecular mechanism of the protection of tanshinone ⅡA on radiation-induced heart damage through MALAT1-p38MAPK pathway. The present study will provide new targets for the prevention and therapy of RIHD.

放射性心脏病（RIHD）是影响放疗患者疗效甚至导致死亡的重要因素，目前尚无有效防治措施。我们前期研究证实丹参酮ⅡA通过激活p38MAPK信号通路减轻氧化应激损伤及心肌细胞凋亡，对放射性心肌细胞损伤发挥保护作用，但确切机制仍不明确。本研究拟使用大鼠原代心肌细胞和小鼠，构建放射性心肌/心脏损伤的体外和体内实验相结合的模型，体内实验进一步验证丹参酮ⅡA对小鼠放射性心脏损伤的保护作用，同时检测lncRNA-MALAT1表达及p38MAPK信号通路相关蛋白的变化；利用基因沉默和基因过表达的手段研究lncRNA-MALAT1在放射性心脏损伤中的功能及其对p38MAPK的调控作用，从而揭示丹参酮ⅡA保护放射性心脏损伤的分子机制。本项目的研究为放射性心脏损伤的防治提供新的靶点和理论依据。

放射性心脏病（radiation-induced heart disease，RIHD）是影响放疗患者疗效甚至导致死亡的重要因素，目前尚无有效的临床防治措施。我们前期研究证实丹参酮ⅡA通过激活P38 MAPK信号通路减轻氧化应激损伤及心肌细胞凋亡，对放射性心肌细胞损伤发挥保护作用，但确切作用机制仍不明确。本研究通过使用SD大鼠与H9C2心肌细胞，构建体内、外放射性心脏损伤模型。通过体内外实验互相验证，明确X线可诱导放射性心脏损伤，证实丹参酮ⅡA通过调控MAPK信号通路对RIHD发挥了保护作用。进一步利用基因编辑技术，沉默长链非编码RNA Malat1，揭示LncRNA Malat1在放射性心脏损伤中的功能及其对MAPK信号通路的调控作用，从而阐释丹参酮ⅡA保护放射性心脏损伤的作用及分子机制。本项目为临床中医药防治RIHD提供深入、全面、可靠的理论证据，并具有重要的临床转化意义。