The Protective Effects of TLR2/NOD2 Combined Agonist CL429 on 14.1 MeV Neutron-Radiation Damage.

IF 2.7 3区医学 Q2 BIOLOGY

Radiation research Pub Date : 2025-08-29 DOI:10.1667/RADE-24-00243.1

Xiaoting Lin, Qingwei Zhao, Yanlan Xiao, Zhemeng Zhao, Zhao Xu, Yunlong Wang, Mingnian Luo, Laxiangge Li, Hongli Yan, Zhiyong Liu, Jiaming Guo, Fu Gao

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Abstract

High-energy neutron radiation (HENR) induces severe cellular and tissue damage, yet effective prophylactic agents remain limited. In this study, the TLR2/NOD2 co-agonist CL429 was evaluated for its radioprotective potential against 14.1 MeV neutron exposure. A murine HENR model was established, and absorbed doses were calculated using the specific kinetic energy method. Pretreatment with CL429 significantly improved survival outcomes, with survival rates reaching 90% and prolonged survival times observed. CL429 administration markedly increased the organ indices of the spleen, thymus, and testis, reduced splenocyte apoptosis to near-normal levels, and restored leukocyte and platelet counts in the early postirradiation phase. Flow cytometry and Western blot analyses indicated that CL429 upregulated TLR2 and NOD2 expression, accompanied by activation of downstream signaling pathways. These findings suggest that CL429 confers significant protection against neutron radiation-induced injury, potentially through the dual activation of TLR2/NOD2-mediated protective mechanisms.

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TLR2/NOD2联合激动剂CL429对14.1 MeV中子辐射损伤的保护作用

高能中子辐射（HENR）会引起严重的细胞和组织损伤，但有效的预防药物仍然有限。本研究评估了TLR2/NOD2共激动剂CL429对14.1 MeV中子暴露的辐射防护潜力。建立小鼠HENR模型，采用比动能法计算吸收剂量。CL429预处理显著改善了生存结果，生存率达到90%，延长了生存时间。给药CL429显著增加了脾脏、胸腺和睾丸的脏器指数，使脾细胞凋亡减少到接近正常水平，并恢复了放疗后早期的白细胞和血小板计数。流式细胞术和Western blot分析显示，CL429上调了TLR2和NOD2的表达，并激活了下游信号通路。这些发现表明，CL429可能通过双重激活TLR2/ nod2介导的保护机制，对中子辐射诱导的损伤具有显著的保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Radiation research 医学-核医学

CiteScore

5.10

自引率

8.80%

发文量

179

审稿时长

1 months

期刊介绍： Radiation Research publishes original articles dealing with radiation effects and related subjects in the areas of physics, chemistry, biology and medicine, including epidemiology and translational research. The term radiation is used in its broadest sense and includes specifically ionizing radiation and ultraviolet, visible and infrared light as well as microwaves, ultrasound and heat. Effects may be physical, chemical or biological. Related subjects include (but are not limited to) dosimetry methods and instrumentation, isotope techniques and studies with chemical agents contributing to the understanding of radiation effects.