Zhao Shasha,Wu Bibo,Bai Jie,et al.Effect of PD-1 inhibitor on aggravating radiation-induced myocardial injury by catalyzing pyroptosis[J].Chinese Journal of Radiological Medicine and Protection,2024,44(4):255-261
Effect of PD-1 inhibitor on aggravating radiation-induced myocardial injury by catalyzing pyroptosis
Received:July 31, 2023  
DOI:10.3760/cma.j.cn112271-20230731-00026
KeyWords:PD-1 inhibitor  Pyroptosis  Myocardial injury  Irradiation
FundProject:贵州省基础研究计划重点项目ZK[(2022)重点040];国家自然科学基金(81960548)
Author NameAffiliationE-mail
Zhao Shasha Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
 
Wu Bibo Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
 
Bai Jie Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
 
Wang Gang Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
 
Liu Yao Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
 
Wang Yu Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
 
Hu Yinxiang Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
 
Ouyang Weiwei Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
 
Lu Bing Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
 
Su Shengfa Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, Affiliated Cancer Hospital of Guizhou Medical University, Guiyang 550004, China
Department of Oncology, School of Clinical Medicine, Guizhou Medical University, Guiyang 550004, China 
sushengfa2005@163.com 
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Abstract::
      Objective To investigate the effects of programmed cell death protein-1 (PD-1) inhibitor on radiation-induced myocardial injury through the pyroptosis pathway. Method Twenty male C57BL/6 mice were randomized into four groups, namely the control group, the PD-1 inhibitor group, the cardiac radiation group (with a single dose of 20 Gy), and the combined group treated with both cardiac radiation and PD-1 inhibitor, with five mice in each group. At 1 month post-irradiation, echocardiography was performed to assess left ventricular ejection fraction (LVEF), stroke volume (SV), and left ventricular fractional shortening (LVFS); Hematoxylin-eosin (HE) and Masson staining were employed to observe the pathological changes in myocardial tissue; Western blot and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to determine the expression of pyroptosis-related key factors in myocardial tissue such as cysteine aspartate specific proteinase-1 (Caspase-1), gasdermin D (GSDMD), and apoptosis-associated speck-like protein containing CARD (ASC). Enzyme-linked immunosorbent assay (ELISA) was performed to determine the expression of interleukin-18 (IL-18) and interleukin-1β (IL-1β). Furthermore, flow cytometry was used to evaluate the infiltration of myocardial lymphocytes. Results Compared to the radiation group, the mice in the combined group exhibited lower LVEF, FS and SV (t = 4.50, 27.93, 3.11, P < 0.05), more significant myocardial injury and fibrosis, elevated myocardial collagen volume fraction [(2.88 ± 0.27)% vs. (3.81 ± 0.57)%, t = 2.90, P < 0.05)], increased expression of Caspase-1, Caspase-1 p20, GSDMD, GSDMD-N, and ASC (t = 3.14, 3.22, 8.83, 20.29, 2.79, P < 0.05), increased mRNA expression of Caspase-1, GSDMD and ASC (t = 3.09, 2.91, 2.53, P <0.05), increased expression of IL-18 and IL-1β in myocardium and serum (t = 3.46, 3.75, 7.58, 8.24, P < 0.05), and higher percentage of CD8+ T lymphocytes [(38.33 ± 7.92)% vs. (54.70 ± 4.01)%, t = 3.29, P < 0.05]. However, there was no significant difference in the percentage of CD4+ T lymphocytes among the groups (P > 0.05). Conclusions PD-1 inhibitor may catalyze pyroptosis via caspase-1/GSDMD, thus aggravating radiation-induced myocardial injury.
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