PD-1抑制剂对心肌炎症微环境及放射性损伤影响的实验研究

doi:10.3760/cma.j.cn113030-20201203-00587

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Abstract Objective To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment. Methods To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group;Group B was the PD-1 inhibitor group;Group C was the simple irradiation group, with a heart irradiation of 15Gy;Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD⁺₃, CD⁺₃CD⁺₄, CD⁺₃CD₈ lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%,(2.83±1.03)%,(5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar (P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD⁺₃ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01);The absolute value and percentage of CD⁺₃CD4 T lymphocytes were similar among four groups (all P>0.05);The absolute value and percentage of CD⁺₃CD₈ T lymphocytes in group D were significantly higher than those in groups A,B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.

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	Articles by authors
	Zhou Kaiyan
	Liu Lingfeng
	Cao Li
	Wang Gang
	Zhao Chaofen
	Kuang Huaxiang
	Hu Yinxiang
	Zhang Haojia
	Su Shengfa
	Lu Bing

Key words： PD-1 inhibitor Radiation-induced myocardial injury Mouse

Received: 03 December 2020

Fund:Guizhou Provincial Natural Science Foundation ([2020] 1Y338);National Natural Science Foundation of China (81960548);Hospital-level Science and Technology Plan Project of Guizhou Cancer Hospital (YJ2019)

Corresponding Authors: Su Shengfa, Email:sushengfa2005@163.com

Cite this article:

Zhou Kaiyan,Liu Lingfeng,Cao Li et al. Experimentation of effect of PD-1 inhibitor on myocardial inflammation microenvironment and radiation-induced injury[J]. Chinese Journal of Radiation Oncology, 2022, 31(1): 79-84.

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http://journal12.magtechjournal.com/Jweb_fszlx/EN/10.3760/cma.j.cn113030-20201203-00587 OR http://journal12.magtechjournal.com/Jweb_fszlx/EN/Y2022/V31/I1/79

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