| 陈玉中,赵琳,顾佳,堵雅芳,李云虹,段广新,秦立强,徐加英.乳铁蛋白通过调节HMGB1/TLR4炎症反应改善放射性肺损伤[J].中华放射医学与防护杂志,2021,41(3):161-165 |
| 乳铁蛋白通过调节HMGB1/TLR4炎症反应改善放射性肺损伤 |
| Lactoferrin improved radioactive lung damage by regulating HMGB1/TLR4 inflammation |
| 投稿时间：2020-11-09 |
| DOI：10.3760/cma.j.issn.0254-5098.2021.03.001 |
| 中文关键词: 乳铁蛋白 炎症因子 放射 肺损伤 |
| 英文关键词:Lactoferrin Inflammatory cytokine Radiation Lung injury |
| 基金项目:国家自然科学基金（81673101，81703159，81973024，82073482）；中国博士后科学基金（2015M571889）；江苏省高等学校自然科学研究重大项目（18KJA310006）；江苏省博士后科学基金（1601121C） |
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| 中文摘要: |
| 目的 研究乳铁蛋白对放射性肺损伤的防护作用。方法 将15只C57BL/6 J小鼠按随机数表法分为健康对照组、15 Gy照射组（单纯照射组）和乳铁蛋白联合15 Gy照射组（联合组），每组5只。联合组全程饮用10 mg/ml乳铁蛋白水溶液，3 d后单纯照射组和联合组给予单次15 Gy X射线全胸照射。于照后14 d处死，苏木素-伊红（HE）染色观察肺病理组织学改变、酶联免疫吸附法（ELISA）检测血清炎症因子高迁移率族蛋白B1（HMGB1）、肿瘤坏死因子α（TNF-α）、白介素1β（IL-1β）及IL-6的水平，免疫组织化学染色和Western blot法检测肺组织中HMGB1、Toll样受体4（TLR4）、MyD88及核转录因子κB（NF-κB）炎症因子蛋白表达。结果 与健康对照组比较，单纯照射组小鼠肺重明显增加（t=3.20，P<0.05）、肺充血水肿并伴有炎性细胞浸润，血清促炎因子TNF-α健康对照组为（291.80±5.49）pg/ml，单纯照射组为（332.25±22.18）pg/ml，两组比较差异有统计学意义（t=3.07，P<0.05）；免疫组织化学染色显示HMGB1和NF-κB阳性明显增多。肺组织中HMGB1、TLR4、MyD88及NF-κB蛋白的表达明显增加，差异有统计学意义（t=4.04、4.78、3.77、6.14，P<0.05）；与单纯照射组相比，乳铁蛋白干预能显著降低受照小鼠肺重（t=2.18，P<0.05）、HMGB1、TNF-α和IL-1β水平（t=4.67、2.97、3.49，P<0.05）。联合组肺组织中HMGB1和NF-κB表达阳性细胞数减少，并下调HMGB1、TLR4、MyD88及NF-κB蛋白表达水平，差异有统计学意义（t=8.06、9.80、3.07、5.56，P<0.05）。结论 乳铁蛋白能够减轻放射性肺损伤，其机制可能与下调炎症相关的HMGB1/TLR4/MyD88/NF-κB信号通路有关。 |
| 英文摘要: |
| Objective To investigate the protective effect of lactoferrin(Lf) on lung injury in mice exposed to irradiation. Methods C57BL/6 J mice were randomly divided into control group, 15 Gy irradiation group (IR group) and lactoferrin combined 15 Gy irradiation group (Lf+IR group), with 5 mice in each group. The mice in the Lf+15 Gy group drank lactoferrin solution (10 mg/ml) from 3 days before irradiation and contained the whole experiments. Then, single chest 15 Gyirradiation was performed both in the IR and Lf+IR groups. The body weight and other characteristics were monitored during the experiment. The mice were killed at day 14 after irradiation. The lung histopathology was observed by HE staining. Serum inflammatory cytokine such as HMGB1, TNF-α, IL-1β and IL-6 was determined by ELISA method. The expression of inflammatory related protein in lung tissue including HMGB1, TLR4, MyD88 and NF-κB were performed by immune histochemistry and Western blot method. Results Compared with the control group, lung weight was significantly increased (t=3.20, P<0.05), pulmonary hyperemia and inflammatory cell infiltration was observed in the IR group. Exposure also significantly increased serum level of TNF-α[(291.80±5.49)vs.(332.25±22.18)pg/ml](t=3.07, P<0.05), up-regulated the expression of inflammatory related protein in lung tissue (t=4.04, 4.78, 3.77, 6.14, P<0.05). Lactoferrin intervention (Lf+IR group) significantly decreased lung weight (t=2.18, P<0.05), alleviated histopathologic changes, decrease serum levels of HMGB1, TNF-α and IL-1β (t=4.67, 2.97, 3.49, P<0.05). On the other hand, lactoferrin intervention decreased the positive cell number of HMGB1 and NF-κB, and down-regulated the protein expression of HMGB1, TLR4, MyD88 and NF-κB in lung tissues, with significant difference with the IR group (t=8.06, 9.80, 3.07, 5.56, P<0.05). Conclusions Lactoferrin plays the protective effect of radiation-induced lung injury through the downregulation of inflammatory response, such as HMGB1/TLR4/MyD88/NF-κB signaling pathway. |
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