Wang Zhaojia, Jia Ziheng, Zhou Zandong, Zhao Xiaotong, Wang Feng, Zhang Xu, Tse Gary, Li Guangping, Liu Yang, Liu Tong
Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China.
Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Front Pharmacol. 2022 Feb 22;13:850735. doi: 10.3389/fphar.2022.850735. eCollection 2022.
Irradiation is an effective treatment for tumors but has been associated with cardiac dysfunction. However, the precise mechanisms remain incompletely elucidated. This study investigated the long-term cardiac damage associated with abdominal irradiation and explored possible mechanisms. Wild-type C57BL6/J mice were divided into two groups: untreated controls (Con) and treatment group receiving 15 Gy of abdominal gamma irradiation (AIR). Both groups received normal feeding for 12 months. The AIR group showed reductions in left ventricular ejection fraction (LVEF), fractional shortening (FS), left ventricular end-diastolic internal diameter (LVID; d), left ventricular end-diastolic volume (LV Vol. diastolic volume (LV Vol; d) and mitral transtricuspid flow late diastolic filling velocity (MV A). It also showed increased fibrosis, reduced conduction velocity and increased conduction heterogeneity. Non-targeted metabolomics showed the differential metabolites were mainly from amino acid metabolism. Further KEGG pathway annotation and enrichment analysis revealed that abnormalities in arginine and proline metabolism, lysine degradation, d-arginine and d-ornithine metabolism, alanine, aspartate and glutamate metabolism, and arginine biosynthesis. Abdominal irradiation causes long-term damage to the non-irradiated heart, as reflected by electrical and structural remodeling and mechanical dysfunction associated with abnormal amino acid biosynthesis and metabolism.
放射治疗是治疗肿瘤的一种有效方法,但与心脏功能障碍有关。然而,其确切机制仍未完全阐明。本研究调查了腹部放疗相关的长期心脏损伤,并探讨了可能的机制。将野生型C57BL6/J小鼠分为两组:未治疗的对照组(Con)和接受15 Gy腹部伽马射线照射(AIR)的治疗组。两组均正常喂养12个月。AIR组左心室射血分数(LVEF)、缩短分数(FS)、左心室舒张末期内径(LVID;d)、左心室舒张末期容积(LV Vol;d)和二尖瓣跨三尖瓣血流舒张晚期充盈速度(MV A)降低。还表现为纤维化增加、传导速度降低和传导异质性增加。非靶向代谢组学显示差异代谢物主要来自氨基酸代谢。进一步的KEGG通路注释和富集分析显示精氨酸和脯氨酸代谢、赖氨酸降解、d-精氨酸和d-鸟氨酸代谢、丙氨酸、天冬氨酸和谷氨酸代谢以及精氨酸生物合成存在异常。腹部放疗会对未受照射的心脏造成长期损伤,表现为与异常氨基酸生物合成和代谢相关的电重构、结构重构和机械功能障碍。
Front Pharmacol. 2022-2-22
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