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中华移植杂志(电子版) ›› 2023, Vol. 17 ›› Issue (01) : 42 -46. doi: 10.3877/cma.j.issn.1674-3903.2023.01.006

论著

髓源性抑制细胞通过抑制炎症反应减轻小鼠肾脏缺血再灌注损伤
张星哲1, 郑秉暄1, 邓格1, 豆猛1, 石玉婷1, 卫田1, 郭映聪1, 韩锋2, 赵艳龙3, 丁晨光1, 田普训1,()   
  1. 1. 710061 西安交通大学第一附属医院肾脏病医院肾移植科 西安交通大学器官移植研究所
    2. 710068 西安,陕西省人民医院烧伤整形医学美容外科
    3. 710003 西安,陕西省中医医院肾病医院血液透析室
  • 收稿日期:2023-01-16 出版日期:2023-02-25
  • 通信作者: 田普训
  • 基金资助:
    国家自然科学基金(81870514,82100798); 陕西省重大基础研究项目(2017ZDJC-09)

Myeloid-derived suppressor cells alleviate renal ischemia-reperfusion injury in mice by inhibiting inflammatory response

Xingzhe Zhang1, Bingxuan Zheng1, Ge Deng1, Meng Dou1, Yuting Shi1, Tian Wei1, Yingcong Guo1, Feng Han2, Yanlong Zhao3, Chenguang Ding1, Puxun Tian1,()   

  1. 1. Department of Kidney Transplantation, Division of Kidney Diseases, First Affiliated Hospital, Xi′an Jiaotong University School of Medicine, Institute of Organ Transplantation, Xi′an Jiaotong University, Xi′an 710061, China
    2. Department of Burn and Plastic Surgery, Shaanxi Provincial People′s Hospital, Xi′an 710068, China
    3. Department of Hemodialysis, Hospital of Nephropathy, Shaanxi Provincial Hospital of Chinese Medicine, Xi′an 710003, China
  • Received:2023-01-16 Published:2023-02-25
  • Corresponding author: Puxun Tian
引用本文:

张星哲, 郑秉暄, 邓格, 豆猛, 石玉婷, 卫田, 郭映聪, 韩锋, 赵艳龙, 丁晨光, 田普训. 髓源性抑制细胞通过抑制炎症反应减轻小鼠肾脏缺血再灌注损伤[J/OL]. 中华移植杂志(电子版), 2023, 17(01): 42-46.

Xingzhe Zhang, Bingxuan Zheng, Ge Deng, Meng Dou, Yuting Shi, Tian Wei, Yingcong Guo, Feng Han, Yanlong Zhao, Chenguang Ding, Puxun Tian. Myeloid-derived suppressor cells alleviate renal ischemia-reperfusion injury in mice by inhibiting inflammatory response[J/OL]. Chinese Journal of Transplantation(Electronic Edition), 2023, 17(01): 42-46.

目的

探讨髓源性抑制细胞(MDSC)对小鼠肾脏缺血再灌注损伤(IRI)的作用及其可能机制。

方法

15只雄性C57BL/6小鼠分为假手术组、IRI组、IRI+MDSC组,每组5只。所有小鼠采取背部双侧切口,切除左肾。假手术组小鼠暴露右肾50 min后缝合,IRI组夹闭右侧肾蒂50 min后开放灌注,IRI+MDSC组于开放灌注1 h内经尾静脉输注使用C57BL/6小鼠骨髓细胞诱导的MDSC。恢复灌注后24h,留取小鼠血液及肾脏和脾脏组织标本,观察肾组织病理变化,检测血尿素氮和肌酐水平。ELISA检测血清中细胞因子TNF-α、IFN-γ、IL-6和IL-10水平。流式细胞术检测脾脏中T细胞活化。符合正态分布的计量数据以均数±标准差(±s)表示,采用单因素方差分析比较。

结果

与IRI组相比,IRI+MDSC组小鼠肾功能明显改善,血尿素氮和血清肌酐水平均低于IRI组([(29.6±3.1)和(34.1±1.4)mmol/L,(105±13)和(176±20)μmol/L,P均<0.05]。IRI+MDSC组肾小管上皮细胞坏死程度、范围及炎性细胞浸润程度较IRI组减轻,Paller评分优于IRI组[(55.0±3.0)和(40.6±6.7)分,P<0.05)]。IRI+MDSC组血清中促炎性细胞因子水平均低于IRI组(P均<0.05),TNF-α分别为(452±55)和(605±73)pg/mL,IFN-γ分别为(405±101)和(576±76)pg/mL,IL-6分别为(459±37)和(863±20)pg/mL;而具有抗炎作用的细胞因子IL-10水平则高于IRI组,分别为(1519±244)和(926±66)pg/mL。同时,IRI+MDSC组小鼠脾脏中活化的CD4T细胞和CD8T细胞水平均低于IRI组,分别为(15.6±1.3)%和(20.2±1.4)%、(31.8±1.8)%和(40.4±2.0)%,差异均有统计学意义(P均<0.05)。

结论

体外诱导MDSC可通过抑制IRI后机体的炎症反应,减轻肾损伤。

Objective

To investigate the effect and mechanism of myeloid-derived suppressor cells (MDSCs) on renal ischemia-reperfusion injury (IRI) in mice.

Methods

A total of 15 male C57BL/6 mice were randomly divided into Sham group (n=5), IRI group (n=5), IRI combined with MDSCs transfusion group (IRI+ MDSC group, n=5). Twenty-four hours after perfusion, blood and kidney tissue samples of mice were collected, and the pathological changes of kidney tissue were observed by hematoxylin-eosin (HE) staining, and the contents of blood urea nitrogen (BUN) and serum creatinine (Cr) were detected. Serum levels of cytokines TNF-α, IFN-γ, IL-6 and IL-10 were detected by ELISA. T-cell activation in spleen was detected by flow cytometry. One-way ANOVA was used to compare the differences between multiple groups.

Results

Compared with the IRI group, the IRI+ MDSC group showed significantly improved renal function [Cr: (105±13) and (176±20) μmol/L, BUN: (34.1±1.4) and (29.6±3.1) mmol/L, P<0.05]. The necrosis degree and range of renal tubular epithelial cells and inflammatory cell infiltration degree were reduced in the IRI+ MDSC group. Paller scores were better in the IRI+ MDSC group than those in the IRI group [(55.0±3.0) vs. (40.6±6.7), P<0.05]. Serum levels of pro-inflammatory cytokines [TNF-α: (452±55) vs. (605±73) pg/mL, IFN-γ: (405±101) vs. (576±76) pg/mL, and IL-6: (459±37) vs. (863±20) pg/mL] in the IRI+ MDSC group were lower than those in IRI group (all P<0.05), respectively. However, the level of anti-inflammatory cytokine IL-10 was higher in the IRI+ MDSC group [(1519±244) pg/mL]. At the same time, the levels of activated CD4+ T cells and CD8+ T cells in spleen of the IRI+ MDSC group were lower than those of the IRI group, which were (15.6±1.3)% and (20.2±1.4)%, (31.8±1.8)% and (40.4±2.0)%, respectively, and the differences were statistically significant (all P<0.05).

Conclusion

MDSCs induced in vitro can alleviate renal injury by inhibiting the inflammatory response after IRI.

图1 GM-CSF联合PGE2体外诱导的MDSC表面标志物及其抑制功能实验注:GM-CSF.粒细胞-巨噬细胞集落刺激因子;PGE2.前列腺素E2; MDSC.髓源性抑制细胞;a和b.流式细胞术检测MDSC表面标志物及比例;c.流式细胞术检测MDSC对CD8 T细胞增殖的抑制功能;*.P<0.05
表1 三组小鼠肾功能、细胞因子和T细胞活化水平比较(±s)
图2 三组小鼠恢复灌注后24 h肾组织病理检查结果(HE ×400)注:IRI.缺血再灌注损伤;MDSC.髓源性抑制细胞;a.假手术组;b. IRI组;c. IRI+MDSC组
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