Gu Anxin, Jie Yamin, Sun Liang, Zhao Shuping, E Mingyan, You Qingshan
Department of Radiotherapy, the Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of Radiotherapy, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
PLoS One. 2015 Sep 2;10(9):e0137337. doi: 10.1371/journal.pone.0137337. eCollection 2015.
Radiation-induced heart disease (RIHD), which is a serious side effect of the radiotherapy applied for various tumors due to the inevitable irradiation of the heart, cannot be treated effectively using current clinical therapies. Here, we demonstrated that rhNRG-1β, an epidermal growth factor (EGF)-like protein, protects myocardium tissue against irradiation-induced damage and preserves cardiac function. rhNRG-1β effectively ameliorated irradiation-induced myocardial nuclear damage in both cultured adult rat-derived cardiomyocytes and rat myocardium tissue via NRG/ErbB2 signaling. By activating ErbB2, rhNRG-1β maintained mitochondrial integrity, ATP production, respiratory chain function and the Krebs cycle status in irradiated cardiomyocytes. Moreover, the protection of irradiated cardiomyocytes and myocardium tissue by rhNRG-1β was at least partly mediated by the activation of the ErbB2-ERK-SIRT1 signaling pathway. Long-term observations further showed that rhNRG-1β administered in the peri-irradiation period exerts continuous protective effects on cardiac pump function, the myocardial energy metabolism, cardiomyocyte volume and interstitial fibrosis in the rats receiving radiation via NRG/ErbB2 signaling. Our findings indicate that rhNRG-1β can protect the myocardium against irradiation-induced damage and preserve cardiac function via the ErbB2-ERK-SIRT1 signaling pathway.
放射性心脏病（RIHD）是由于心脏不可避免地受到照射而在各种肿瘤放疗过程中出现的一种严重副作用，目前的临床治疗方法无法有效治疗该病。在此，我们证明了重组人神经调节蛋白-1β（rhNRG-1β），一种表皮生长因子（EGF）样蛋白，可保护心肌组织免受辐射诱导的损伤并维持心脏功能。rhNRG-1β通过NRG/ErbB2信号通路有效改善了成年大鼠来源的培养心肌细胞和大鼠心肌组织中辐射诱导的心肌核损伤。通过激活ErbB2，rhNRG-1β维持了受辐射心肌细胞中线粒体的完整性、ATP生成、呼吸链功能和三羧酸循环状态。此外，rhNRG-1β对受辐射心肌细胞和心肌组织的保护作用至少部分是由ErbB2-ERK-SIRT1信号通路的激活介导的。长期观察进一步表明，在辐射期间给予rhNRG-1β通过NRG/ErbB2信号通路对接受辐射的大鼠的心脏泵功能、心肌能量代谢、心肌细胞体积和间质纤维化发挥持续的保护作用。我们的研究结果表明，rhNRG-1β可通过ErbB2-ERK-SIRT1信号通路保护心肌免受辐射诱导的损伤并维持心脏功能。
