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1.中山大学医学院,广东 深圳 518107
2.中山大学附属第三医院神经内科,广东 广州 510630
陈海莲,第一作者,研究方向:神经炎症、生物与医药,E-mail:chenhlian@mail2.sysu.edu.cn
收稿日期:2024-10-29,
录用日期:2025-02-05,
纸质出版日期:2025-03-20
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陈海莲,王玉鸽,崔宇等.支架蛋白PDLIM5增强小胶质细胞吞噬及其在多发性硬化中作用的研究[J].中山大学学报(医学科学版),2025,46(02):179-185.
CHEN Hailian,WANG Yuge,CUI Yu,et al.Enhancement of Microglial Phagocytosis by Scaffold Protein PDLIM5 and Its Role in Multiple Sclerosis[J].Journal of Sun Yat-sen University(Medical Sciences),2025,46(02):179-185.
陈海莲,王玉鸽,崔宇等.支架蛋白PDLIM5增强小胶质细胞吞噬及其在多发性硬化中作用的研究[J].中山大学学报(医学科学版),2025,46(02):179-185. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2025.0201.
CHEN Hailian,WANG Yuge,CUI Yu,et al.Enhancement of Microglial Phagocytosis by Scaffold Protein PDLIM5 and Its Role in Multiple Sclerosis[J].Journal of Sun Yat-sen University(Medical Sciences),2025,46(02):179-185. DOI: 10.13471/j.cnki.j.sun.yat-sen.univ(med.sci).2025.0201.
目的
2
探究支架蛋白PDLIM5在多发性硬化(MS)患者及小鼠小胶质细胞系BV2中的表达情况并探讨其对小胶质细胞吞噬功能的影响。
方法
2
共收集24例MS患者的外周血和6例健康志愿者的样本作为对照,通过实时荧光定量PCR检测PDLIM5的表达水平;使用脂多糖(LPS,1 µg/mL)处理小鼠小胶质细胞系BV2建立神经炎症细胞模型,通过蛋白免疫印迹法检测PDLIM5的表达水平;通过BV2细胞转染PDLIM5 shRNA质粒或PDLIM5过表达质粒,分析PDLIM5的表达对细胞吞噬功能的影响。
结果
2
实时荧光定量PCR结果显示,与健康对照组相比,MS患者的单核细胞[2.78(0.70~6.86)
vs.
0.54(0.39~1.51),
P
=0.036]和淋巴细胞[1.62(0.90~2.26)
vs.
0.11(0.05~0.21),
P
<
0.001]中PDLIM5表达水平显著升高;蛋白免疫印迹结果显示,LPS刺激BV2后PDLIM5表达水平显著升高(
P
<
0.05);质粒转染实验结果显示,敲低PDLIM5后抑制BV2对台盼蓝的吞噬能力(
P
<
0.05),而过表达PDLIM5增强BV2对台盼蓝的吞噬能力(
P
<
0.001)。
结论
2
神经炎症状态下,PDLIM5表达水平升高,可促进小胶质细胞的吞噬功能。
Objective
2
To investigate the expression of scaffold protein PDLIM5 in multiple sclerosis (MS) patients and the mouse microglial cell line BV2, and to explore its effects on the phagocytosis of microglial cells.
Methods
2
Peripheral blood samples were collected from 24 MS patients and 6 healthy volunteers as controls. The expression levels of PDLIM5 were detected by real-time quantitative PCR. A neuroinflammation cell model was established by treating the mouse microglial cell line BV2 with lipopolysaccharide (LPS, 1 µg/mL). The expression levels of PDLIM5 were measured by Western Blot. The effect of PDLIM5 expression on phagocytosis was analyzed by transfecting BV2 cells with PDLIM5 shRNA plasmids or PDLIM5 overexpression plasmids.
Results
2
Real-time quantitative PCR results showed that compared with the healthy control group, the expression level of PDLIM5 from the MS patients was significantly increased in monocytes [2.78 (0.70-6.86)
vs.
0.54 (0.39-1.51),
P
=0.036] and lymphocytes [1.62 (0.90-2.26)
vs.
0.11 (0.05-0.21),
P
<
0.001]. Western Blot results indicated that PDLIM5 expression was significantly upregulated in BV2 cells following LPS stimulation (
P
<
0.05). Plasmid transfection experiments demonstrated that knockdown of PDLIM5 inhibited the phagocytic capacity of BV2 cells as measured by trypan blue uptake (
P
<
0.05), while overexpression of PDLIM5 enhanced the phagocytic ability of BV2 cells (
P
<
0.001).
Conclusion
2
Under neuroinflammatory conditions, PDLIM5 expression is elevated, and this upregulation promotes the phagocytosis of microglial cell.
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