SLPI介导Kupffer细胞极化调控RILD的作用初探

袁楠; 吕小立; 沈佳琪; 焦旸

0
0
浏览
下载

摘要
关键词
基金信息
论文图表
动态公开评议
相关论文
评论

SLPI介导Kupffer细胞极化调控RILD的作用初探

首发时间：2024-02-05

袁楠 ^{1
2}
袁楠（1998-），女，放射生物学
吕小立 ^{1
2}
吕小立（1995-），男，肿瘤放射治疗学
沈佳琪 ^{1
2} 焦旸 ^{1
2}
焦旸（1977-），女，教授，博导，放射生物学

1、放射医学与辐射防护国家重点实验室
2、苏州大学医学部放射医学与防护学院，苏州 215123

摘要：目的：初步探索分泌性白细胞蛋白酶抑制剂（Secretory leukocyte protease inhibitor ，SLPI）介导电离辐射诱导枯否细胞（Kupffer cells，KCs）极化，从而参与调控放射性肝损伤（radiation-induced liver disease，RILD）发生发展的生物学作用。方法：采用30 Gy X射线单次局部照射6-8周龄雄性C57/BL6J小鼠肝脏，24h后通过流式、肝功能检测和组织病理学检查验证RILD以及KCs变化。实时荧光定量PCR（qPCR）检测电离辐射诱导小鼠单核巨噬细胞系RAW264.7及原代肝KCs极化过程中SLPI表达情况。随后采用siRNA在巨噬细胞中下调SLPI的表达，经免疫印迹实验（Western blot）检测电离辐射后其对巨噬细胞极化的调控作用。此外通过流式细胞术分析探讨SLPI对电离辐射诱导KCs极化调控RILD的具体作用。结果：通过血生化分析、肝脏组织病理检测及流式细胞术分析，发现RILD的小鼠肝组织中KCs的M1与M2的比值增加（p<0.01），即KCs由M2型向M1型极化。经qPCR检测发现，电离辐射可诱导RAW264.7及原代肝KCs中SLPI的表达增加（p<0.01），且增加趋势与M1/M2的增加趋势正相关。与对照组相比，敲低SLPI后可见受照射后M1型巨噬细胞分泌的炎性因子白介素1β（IL-1β）、白介素6（IL-6）及肿瘤坏死因子（TNFα）表达降低，并且可显著降低辐射诱导肝细胞的凋亡率（p<0.05）。结论：RILD的发生伴有肝脏巨噬细胞极化状态显著变化，电离辐射诱导的KCs分泌SLPI可能通过介导肝巨噬细胞的极化，参与RILD的发生发展。

关键词：放射性肝损伤肝枯否细胞巨噬细胞极化 SLPI

For information in English, please click here

Preliminary studies on the efferts of SLPI-mediated Kupffer cell polarisation in regulating radiation-induced liver disease

Yuan Nan ^{1
2}
袁楠（1998-），女，放射生物学
Lv Xiaoli ^{1
2}
吕小立（1995-），男，肿瘤放射治疗学
Shen Jiaqi ^{1
2} Jiao Yang ^{1
2}
焦旸（1977-），女，教授，博导，放射生物学

1、State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection Soochow University, Suzhou 215123, China
2、Soochow State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection Soochow University, Suzhou 215123, China

Abstract：Objective: The primary aim is to explore the biological role of Secretory Leukocyte Protease Inhibitor (SLPI) in mediating the polarization of Kupffer cells (KCs) induced by ionizing radiation, thereby participating in the regulation of the onset and progression of radiation-induced liver disease (RILD). Methods: LiverSLPI induces Kupffer cells polarization in ionizing radiation involved in radioactive liver injury regions of 6-8 weeks old male C57/BL6J mice were exposed to a single dose of 30 Gy X-ray irradiation. RILD and changes in KCs were validated 24 hours later via flow cytometry, liver function tests, and histopathological examination. The expression of SLPI during the polarization of mouse monocyte-macrophage cell line RAW264.7 and primary liver KCs induced by ionizing radiation was detected using real-time quantitative PCR (qPCR). SLPI expression in macrophages was downregulated using siRNA, and its regulatory role in macrophage polarization post-irradiation was analyzed via Western blot. Additionally, the specific role of SLPI in regulating RILD by modulating the polarization of ionizing radiation-induced KCs was explored through flow cytometry. Results: Biochemical blood analysis, liver tissue histopathology, and flow cytometry indicated an increase in the M1/M2 ratio of KCs in mouse liver tissues with RILD (p<0.01), signifying a polarization shift from M2 to M1 phenotype. qPCR revealed that ionizing radiation induced an increase in SLPI expression in RAW264.7 and primary liver KCs (p<0.01), correlating positively with the M1/M2 ratio increase. Compared to the control group, knockdown of SLPI led to a decrease in the expression of inflammatory cytokines IL-1β, IL-6, and TNFα secreted by irradiated M1 macrophages, and significantly reduced the apoptosis rate of radiation-induced hepatocytes (p<0.05). Conclusion: The development of RILD is accompanied by significant changes in the polarization state of liver macrophages. The secretion of SLPI by ionizing radiation-induced KCs may mediate the polarization of liver macrophages, playing a role in the onset and progression of RILD.

Keywords： Radiation-induced liver disease Kupffer cells Macrophage polarization SLPI

基金：

论文图表：

引用

导出参考文献

.txt

.ris

.doc

袁楠，吕小立，沈佳琪，等. SLPI介导Kupffer细胞极化调控RILD的作用初探[EB/OL]. 北京：中国科技论文在线 [2024-02-05]. https://www.paper.edu.cn/releasepaper/content/202402-46.

No.****

动态公开评议

共计0人参与

动态评论进行中

全部评论

0/1000

论文编号	202402-46
论文题目	SLPI介导Kupffer细胞极化调控RILD的作用初探
文献类型
收录期刊	上传封面中文期刊英文期刊期刊名称（中文）期刊名称（英文）年，卷（）上传封面中文专著英文专著书名（中文）书名（英文）出版地出版社出版年上传封面中文译著英文译著书名（中文）书名（英文）出版地出版社出版年上传封面中文论文集英文论文集编者.论文集名称（中文） [c]. 出版地出版社出版年， - 编者.论文集名称（英文） [c]. 出版地出版社出版年，- 上传封面中文文献英文文献期刊名称（中文）期刊名称（英文）日期-- 在线地址http:// 上传封面中文文献英文文献文题（中文）文题（英文）出版地出版社,出版日期-- 上传封面中文文献英文文献文题（中文）文题（英文）出版地出版社,出版日期--
英文作者写法：中外文作者均姓前名后，姓大写，名的第一个字母大写，姓全称写出，名可只写第一个字母，其后不加实心圆点“.”, 作者之间用逗号“，”分隔，最后为实心圆点“.”, 示例1：原姓名写法：Albert Einstein,编入参考文献时写法：Einstein A. 示例2：原姓名写法：李时珍；编入参考文献时写法：LI S Z. 示例3：YELLAND R L,JONES S C,EASTON K S,et al.