文献类型：期刊文献

英文题名：The impact of X-rays on cardiac hydrometabolism and the regulatory role of AS-IV

作者：Zhang, Shangzu[1];Li, Qiyang[1];Dai, Sichao[1];Wang, Yutong[1];Li, Yangyang[1];Chen, Yan[1];Yang, Gengqiang[1];Zhou, Ting[1];Miao, Zhiming[1];Liu, Fuxian[1];Zhang, Liying[1,2,4];Liu, Yongqi[1,2,3]

第一作者：张尚智;张尚珍;张绍重

通信作者：Zhang, LY[1];Liu, YQ[1]

机构：[1]Gansu Univ Chinese Med, Lanzhou, Peoples R China;[2]Gansu Univ Chinese Med, Prov Level Key Lab Mol Med Major Dis & Prevent & T, Lanzhou, Peoples R China;[3]Key Lab Dunhuang Med & Transformat Prov & Minister, Lanzhou, Peoples R China;[4]Gansu Inst Cardiovasc Dis, Lanzhou, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Lanzhou, Peoples R China.|[10735]甘肃中医药大学;

年份：2024

卷号：143

外文期刊名：INTERNATIONAL IMMUNOPHARMACOLOGY

收录：;Scopus(收录号：2-s2.0-85207931788);WOS:【SCI-EXPANDED(收录号:WOS:001348717400001)】；

基金：Chinese Postdoctoral Science Foundation (2021M693794) , National Natural Science Foundation of China Joint Fund for Regional Innovation Development Key Support Project (NO. U23A20502) , National Natural Science Foundation of China (82260882) . Consent for publication All authors reviewed and approved the final manuscript. All authors supported the publication of this manuscript.

语种：英文

外文关键词：Radiation-induced heart disease; Cardiomyocyte edema; HIF-1 alpha; AQPs; AS-IV

摘要：Background: Radiation-induced cardiac injury has emerged as a significant pathological entity, with many studies focusing on the fibrotic changes in myocardial tissue. However, these do not offer solutions for the clinical prevention and treatment of radiation-induced heart disease. Regulating hydrometabolism presents a potential therapeutic target for the management of cardiovascular diseases. This research seeks to explore the impacts of irradiation on cardiac hydrometabolism and its regulatory mechanisms. Methods: The impact of X-ray radiation on cardiac and cardiomyocyte hydrometabolism was studied through in vivo and in vitro experiments, examining the pharmacological effects and mechanisms of PX-478 and AS-IV interventions in cardiomyocytes. Results: 28 days after direct chest irradiation with 20 Gy X-rays, C57BL/6 mice exhibited an increased heart wetto-dry weight ratio, significant enlargement of cardiomyocyte cross-sectional area, and elevated protein expression of HIF-1 alpha, AQP1, AQP4, Cx43, Caspase3, and Bax, with decreased expression of Bcl-2. Irradiation with 6 Gy X-rays induced edema and damage in AC16 and HL-1 cardiomyocytes at 24, 48, and 72 h, with increased expression of HIF-1 alpha, AQP1, AQP4, and Cx43 proteins post-radiation. Inhibition of HIF-1 alpha ameliorated edema and apoptosis in AC16 and HL-1 cardiomyocytes, reducing the expression of HIF-1 alpha, AQP1, AQP4, and Cx43 proteins. AS-IV demonstrated strong binding affinity with HIF-1 alpha, and successfully attenuated the expression levels of HIF-1 alpha, AQP1, AQP4, and Cx43 proteins, alleviating edema, mitochondrial swelling, and apoptosis in AC16 and HL-1 cardiomyocytes. Furthermore, AS-IV improved cardiomyocyte edema by restoring the activity of Na/K-ATPase. Conclusion: Aberrant activation of the HIF-1 alpha/AQPs/Cx43 axis is a key mechanism in X-ray-induced cardiomyocyte edema and damage. AS-IV can ameliorate X-ray induced cardiac damage by regulating hydrometabolism.