石墨烯量子点经自噬依赖途径缓解小鼠急性移植物抗宿主病研究*

doi:10.3969/j.issn.1671-2587.2023.03.003

临床输血与检验 ›› 2023, Vol. 25 ›› Issue (3): 302-310.DOI: 10.3969/j.issn.1671-2587.2023.03.003

石墨烯量子点经自噬依赖途径缓解小鼠急性移植物抗宿主病研究^*

徐亚栋, 李志强

200030 上海交通大学医学院附属第六人民医院

收稿日期:2023-05-09 发布日期:2023-07-10
通讯作者: 李志强,主任医师,主要从事血液病诊治和临床输血基础与应用方面的研究,（E-mail）kcb039@126.com。
作者简介:徐亚栋,主要从事血液病方面的研究,（E-mail）729820985@qq.com。
基金资助:
^*本课题受上海市2020年度“科技创新行动计划”生物医药科技支撑专项项目（No.0S31902900）资助

Graphene Quantum Dots Alleviate Acute Graft-Versus-Host Disease in Mice Through an Autophagy-Dependent Pathway

XU Yadong, LI Zhiqiang

The Sixth People's Hospital of Shanghai Jiaotong University School of Medicine, Shanghai 200030

Received:2023-05-09 Published:2023-07-10

摘要/Abstract

摘要： 目的研究石墨烯量子点（graphene quantum dots,GQDs）对小鼠急性移植物抗宿主病（acute graft-versus-host disease,aGVHD）的干预治疗作用,并探究其机制。方法 ① GQDs干预分组：aGVHD+GQDs组、aGVHD+PBS组和BMT组,每组10只。观察各组小鼠生存期和临床症状,肝、皮肤以及肠组织病理变化情况。应用ELISA方法检测脾脏组织细胞因子TNF-α、IL-1β、IL-10、TGF-β的变化。应用免疫荧光染色F4/80、iNOS、CD206检测脾脏巨噬细胞浸润情况及M1/M2亚群的变化。应用Western blot检测脾脏组织自噬相关蛋白LC-3、p62的变化。② 3-甲基腺嘌呤（3-Methyladenine ,3-MA）阻断自噬分组：aGVHD+GQDs+3-MA组和aGVHD+GQDs+PBS组,每组10只。观察各组小鼠生存期和临床症状,肝、皮肤以及肠组织病理变化情况。应用Western blot检测脾脏组织自噬相关蛋白LC-3、p62的变化。结果 GQDs干预治疗可显著降低aGVHD小鼠脾脏巨噬细胞的浸润,并可使M2型巨噬细胞比例显著增加。另外,GQDs干预治疗可上调aGVHD小鼠脾脏自噬相关蛋白LC3II/I的表达,降低p62的表达,激活自噬通路缓解小鼠aGVHD症状,减轻靶器官病理损伤,延长生存期。3-MA阻断自噬通路可抑制GQDs对aGVHD小鼠干预治疗作用。结论 GQDs可通过自噬依赖的途径缓解小鼠aGVHD。

关键词: 石墨烯量子点, 急性移植物抗宿主病, 巨噬细胞, 自噬, 信号通路

Abstract: Objective To investigate the therapeutic effect of graphene quantum dots (GQDs) on acute graft-versus-host disease (aGVHD) in mice and its mechanism. Methods ① GQDs intervention groupsincluded the aGVHD+GQDs group, aGVHD+PBS group and BMT group, 10 mice in each group. The survival period and clinical symptoms, and the liver, skin and intestinal histopathological changes of mice in each group were observed. ELISA method was done for the changes of TNF-α, IL-1β, IL-10 and TGF-β cytokines in the spleen tissue, immunofluorescence staining of F4/80, iNOS, and CD206 for the infiltration of splenic macrophages and changes of M1/M2 subpopulation, and Western blot for the changes of autophagy-related proteins LC-3 and p62 in the spleen tissue. ② For 3-Methyladenine（3-MA）blocked autophagy, the mice were divided into the aGVHD+GQDs+3-MA group and aGVHD +GQDs+PBS group , 10 in each group. The survival period and clinical signs, as well as the liver, skin and intestinal histopathological changes of mice in each group were observed. Western blot was applied to detect the changes of autophagy-related proteins LC-3 and p62 in the spleen tissues. Results GQDs intervention significantly reduced the infiltration of splenic macrophages in aGVHD mice, but significantly increased the proportion of M2-type macrophages. In addition, this intervention upregulated the expression of autophagy-related protein LC3II/I in the spleen of aGVHD mice, decreased the expression of p62, activated the autophagic pathway to alleviate the symptoms of aGVHD mice, alleviated the pathological damage of target organs, and prolonged the survival. 3-MA blockade of the autophagic pathway inhibited the therapeutic effect of GQDs treatment on aGVHD mice. Conclusion GQDs could alleviate aGVHD in mice through an autophagy-dependent pathway.

Key words: Graphene quantum dots, Acute graft-versus-host disease, Macrophages, Autophagy, Signaling pathways

中图分类号:

R392

徐亚栋, 李志强. 石墨烯量子点经自噬依赖途径缓解小鼠急性移植物抗宿主病研究^*[J]. 临床输血与检验, 2023, 25(3): 302-310.

XU Yadong, LI Zhiqiang. Graphene Quantum Dots Alleviate Acute Graft-Versus-Host Disease in Mice Through an Autophagy-Dependent Pathway[J]. JOURNAL OF CLINICAL TRANSFUSION AND LABORATORY MEDICINE, 2023, 25(3): 302-310.

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石墨烯量子点经自噬依赖途径缓解小鼠急性移植物抗宿主病研究^*

Graphene Quantum Dots Alleviate Acute Graft-Versus-Host Disease in Mice Through an Autophagy-Dependent Pathway

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