胸部肿瘤疾病的放射治疗是恶性肿瘤综合治疗的重要组成部分,而邻近纵隔的心脏在放疗时不可避免地受到辐射损伤，探索心肌抗辐照维护微循环的保护机制和新策略尤为重要。我们采用动物单心脏及心肌细胞辐照的研究结果表明,垂体腺苷酸环化酶激活肽(PACAP38)能有效地修复辐照小鼠心脏的舒张功能障碍及组织损伤，并显著增强心肌细胞抗氧化应激关键因子NRF2的生物活性。敲低心肌细胞内NRF2的表达可部分降低PACAP38缓解辐照后心肌细胞活力下降的作用。因此，本研究拟采用动物心脏及心肌细胞分次辐照模型，基于动物心功能检测平台，深入研究PACAP38对心脏损伤的作用，阐明PACAP38结合特异性受体，通过活化MAPK蛋白激酶级联反应，进一步加强激活NRF2/HO-1中央信号通路对放射性心脏损伤的保护机制。为胸部肿瘤放射治疗的心脏安全性提供有效的早期干预新手段。

Radiation-induced heart disease (RIHD) is a common sequelae of thoracic irradiation, the occurrence of oxidative stress and pro-inflammatory reaction is associated with the development of RIHD. It is especially important to explore new protective strategy against RIHD. Exposure of murine heart and cardiomyocytes to radiation, we found that pituitary adenylate cyclase activating polypeptide 38 (PACAP38) could effectively recover diastolic dysfunction and tissue damage of mouse heart by irradiation in vivo. PACAP38 significantly activated the expression of NRF2, a key factor of anti-oxidative stress in cardiomyocytes, and reduced the apoptosis and cell cycle arrest of myocardial cells with irradiation. The protective effect of PACAP38 was partially blocked by NRF2 siRNA silencing. In the present study, we propose to utilize mouse model and primary cultured myocardial cells exposed to fractionated irradiation, and to examine the cardiac function by ultrasound platform. The cardioprotective function of PACAP38 will be studied intensively on mouse models of radiation-induced cardiac injury. We will elucidate the protective mechanism of PACAP38 binding to specific receptor to activate MAPK signaling cascade leading to further activation of NRF2/HO-1 signling pathway in RIHD. The result will be able to demonstrate the cardioprotective effect of PACAP38 in cardiac radiation toxicity, and will attempt to develop effective tool for de novo intervention of myocardial injury, in radiation treatment of thoracic malignant tumors.