贵州医科大学学报

2019, v.44;No.221(02) 141-146+152

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FcγRIIB缺失促进顺铂诱导的急性肾损伤小鼠肾组织巨噬细胞浸润
Fcγ RIIB Deficiency Promotes Macrophage Infiltration in Cisplatin-induced Mouse Acute Kidney Injury

金筱茜,吴通前,马岚,袁锐,杨丹,周玲,高健,王珺,周海燕,余芳
JIN Xiaoqian,WU Tongqian,MA Lan,YUAN Rui,YANG Dan,ZHOU Ling,GAO Jian,WANG Jun,ZHOU Haiyan,YU Fang

摘要(Abstract):

目的:探究巨噬细胞表面免疫球蛋白Fc gamma IIB受体(FcγRIIB)缺失对顺铂诱导的急性肾损伤(AKI)小鼠巨噬细胞浸润及肾组织损伤的影响。方法:8~10周龄雄性野生型(WT) C57 BL/6及FcγRIIB基因敲除(FcγRIIB-/-)小鼠随机分成WT对照组(WC),WT AKI模型组(WM),FcγRIIB-/-对照组(FC)和FcγRIIB-/-AKI模型组(FM),两个模型组予20 mg/kg体质量腹腔注射顺铂,两个对照组予等量的生理盐水;造模后3 d取血检测血清肌酐(Scr)和尿素氮(BUN)、处死小鼠取肾组织HE染色,免疫组织化学检测观察肾组织巨噬细胞(CD68)浸润情况,ELISA检测组肾组织匀浆单核细胞趋化蛋白-1(MCP-1)和肿瘤坏死因子-α(TNF-α)含量,流式细胞术检测巨噬细胞CD86(M1)和CD206(M2)亚型,荧光定量聚合酶链反应(q-PCR)测肾组织MCP-1(CCL2)、MCP-1α(CCL3)及MCP-1β(CCL4) mRNA相对表达量。结果:与FC组及WC组比较,WM组及FM组血清BUN和Scr水平升高、HE染色显示肾损伤严重、肾组织MCP-1及TNF-α水平升高、CD68+巨噬细胞浸润增多、CCL2及CCL4 mRNA水平增加,差异均有统计学意义(P <0. 05),且FM组较WM组改变更明显(P <0. 05);流式细胞术结果显示各组小鼠肾组织巨噬细胞亚型差异无统计学意义(P> 0. 05)。结论:FcγRIIB缺失可能引起肾组织巨噬细胞浸润增多而加重顺铂引起的AKI。
Objective: To evaluate the effect of the expression of macrophage surface IgG FcγRIIB on macrophage infiltration and the progress of a cisplatin-induced acute kidney injury( AKI) mouse model. Methods: Both 8 ~ 10 week old male wide type( W) C57 BL/6 and FcγRIIB knock out( FcγRIIB-/-,F) mice were randomly divided into the control group( C) and the AKI group( M)( n= 5 per group) : WC,WM,FC and FM. WM and FM mice were intraperitoneally administrated with single dose of 20 mg/Kg cisplatin to establish acute kidney injury( AKI) mouse model,and the control mice( WC and FC) were given the same volume of saline. Mice were sacrificed on day 3 after the treatment. The levels of serum creatinine( Scr) and blood urea nitrogen( BUN) were measured. The pathological changes of kidney tissue were evaluated using HE-staining and immunohistochemical( IHC) analyses. IHC with CD86 antibody detection was performed on consecutive sections to determine macrophage infiltration. Kidney homogenates were prepared to evaluate TNF-α and MCP-1 using enzyme linked immunosorbent assay( ELISA). Macrophage phenotyping was evaluated using flow cytometric analysis. Total RNA from kidneys was extracted for qRT-PCR analysis targeting CCL2,CCL3,CCL4. Results: Cisplatin treatment induced higher levels of serum SCr and BUN and elevated inflammatory cytokines and chemokines( TNF-α and MCP-1) in the homogenate of renal tissue from FcγRIIB-/-mice when compared to the WT mice. Semi-quantitative histological injury scores were significantly higher in cisplatin-treated FcγRIIB deficient mice than in WT controls. Cisplatin injection induced increased macrophages infiltration in the mouse renal tissue,which was more apparent in mice lacking FcγRIIB,whereas similar frequencies of macrophage subtypes were seen in the renal tissue in four groups. Conclusion: FcγRIIB deficiency potentially promotes macrophage infiltration leading to more severe acute kidney injury.

关键词(KeyWords): 巨噬细胞;免疫球蛋白Fc受体;顺铂;急性肾损伤;单核细胞趋化蛋白-1;肿瘤坏死因子-α
macrophage;immunoglobulin Fc receptor;cisplatin;acute kidney injury;monocyte chemoattractant protein-1;tumor necrosis factor α

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(81560266)

作者(Author): 金筱茜,吴通前,马岚,袁锐,杨丹,周玲,高健,王珺,周海燕,余芳
JIN Xiaoqian,WU Tongqian,MA Lan,YUAN Rui,YANG Dan,ZHOU Ling,GAO Jian,WANG Jun,ZHOU Haiyan,YU Fang

DOI: 10.19367/j.cnki.1000-2707.2019.02.004

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