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HL-003 对小鼠放射性唾液腺损伤的防护作用及其机制。

Radioprotective effects and mechanism of HL-003 on radiation-induced salivary gland damage in mice.

机构信息

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Science, Tianjin, 300192, China.

Department of Oral Medicine, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, 300041, China.

出版信息

Sci Rep. 2022 May 19;12(1):8419. doi: 10.1038/s41598-022-12581-y.

DOI:10.1038/s41598-022-12581-y
PMID:35589816
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9120142/
Abstract

Ionizing radiation (IR) can cause damage to the structure and function of salivary glands. Our research group independently synthesized the ROS scavenger, HL-003. The aim of this study was to explore the protective effects and underlying mechanisms of HL-003 on radiation-induced salivary gland injury. Salivary flow rate measurement, H&E staining, immunohistochemistry, FRAP, TUNEL, and western blotting were used to evaluate the radioprotective effect on salivary glands. The results showed that HL-003 protected the salivary secretion function by protecting the AQP-5 protein, on the salivary epithelial cell membrane, from IR damage. HL-003 reduced oxidative stress in the salivary gland by regulating the expression of ROS-related proteins NOX4, SOD2, and 8-OHdG. Furthermore, HL-003 downregulated the expression of p-p53, Bax, caspase 3, and caspase 9, and upregulated the expression of Bcl-2, suggesting that it could inhibit the activation of p53 to reduce cell apoptosis. In conclusion, HL-003 is an effective radioprotector that prevents damage of the radiation-induced salivary gland.

摘要

电离辐射 (IR) 可导致唾液腺结构和功能受损。我们的研究小组自主合成了活性氧 (ROS) 清除剂 HL-003。本研究旨在探讨 HL-003 对放射性唾液腺损伤的保护作用及其机制。通过唾液流率测定、H&E 染色、免疫组织化学、FRAP、TUNEL 和 Western blot 等方法评价 HL-003 对唾液腺的放射防护作用。结果表明,HL-003 通过保护细胞膜上的 AQP-5 蛋白免受 IR 损伤,保护唾液分泌功能。HL-003 通过调节 ROS 相关蛋白 NOX4、SOD2 和 8-OHdG 的表达来减轻唾液腺中的氧化应激。此外,HL-003 下调了 p-p53、Bax、caspase 3 和 caspase 9 的表达,上调了 Bcl-2 的表达,提示其可能通过抑制 p53 的激活来减少细胞凋亡。总之,HL-003 是一种有效的放射保护剂,可防止辐射引起的唾液腺损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/3c799299e018/41598_2022_12581_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/b5a29bda4ef6/41598_2022_12581_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/691ac7acfce4/41598_2022_12581_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/93fe82f20b18/41598_2022_12581_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/d1f15b82d962/41598_2022_12581_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/786fbea6f8c2/41598_2022_12581_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/3c799299e018/41598_2022_12581_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/b5a29bda4ef6/41598_2022_12581_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/691ac7acfce4/41598_2022_12581_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/93fe82f20b18/41598_2022_12581_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/d1f15b82d962/41598_2022_12581_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/786fbea6f8c2/41598_2022_12581_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b55f/9120142/3c799299e018/41598_2022_12581_Fig6_HTML.jpg

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