留言板

尊敬的读者、作者、审稿人, 关于本刊的投稿、审稿、编辑和出版的任何问题, 您可以本页添加留言。我们将尽快给您答复。谢谢您的支持!

姓名
邮箱
手机号码
标题
留言内容
验证码

骨髓间充质干细胞对小鼠缺血-再灌注急性肾损伤中IL-10和TNF-α表达的影响

蔺晨雨 陈文 马锡慧 孔祥瑞 樊文梅 韩永 肖漓 石炳毅

蔺晨雨, 陈文, 马锡慧, 等. 骨髓间充质干细胞对小鼠缺血-再灌注急性肾损伤中IL-10和TNF-α表达的影响[J]. 器官移植, 2021, 12(5): 563-570. doi: 10.3969/j.issn.1674-7445.2021.05.010
引用本文: 蔺晨雨, 陈文, 马锡慧, 等. 骨髓间充质干细胞对小鼠缺血-再灌注急性肾损伤中IL-10和TNF-α表达的影响[J]. 器官移植, 2021, 12(5): 563-570. doi: 10.3969/j.issn.1674-7445.2021.05.010
Lin Chenyu, Chen Wen, Ma Xihui, et al. Effect of bone marrow mesenchymal stem cell on the expression of IL-10 and TNF-α in mice with ischemia-reperfusion acute kidney injury[J]. ORGAN TRANSPLANTATION, 2021, 12(5): 563-570. doi: 10.3969/j.issn.1674-7445.2021.05.010
Citation: Lin Chenyu, Chen Wen, Ma Xihui, et al. Effect of bone marrow mesenchymal stem cell on the expression of IL-10 and TNF-α in mice with ischemia-reperfusion acute kidney injury[J]. ORGAN TRANSPLANTATION, 2021, 12(5): 563-570. doi: 10.3969/j.issn.1674-7445.2021.05.010

骨髓间充质干细胞对小鼠缺血-再灌注急性肾损伤中IL-10和TNF-α表达的影响

doi: 10.3969/j.issn.1674-7445.2021.05.010
基金项目: 

军队医学科技青年培育计划 18QNP035

详细信息
    作者简介:

    蔺晨雨,女,1992年生,硕士研究生,研究方向为移植免疫学,Email:lcylinchenyu@163.com

    通讯作者:

    肖漓,女,1972年生,博士,主任技师,硕士研究生导师,研究方向为移植免疫学、感染免疫学和免疫学技术,E-mail: xiaolilab309@163.com

  • 中图分类号: R617, R364.5

Effect of bone marrow mesenchymal stem cell on the expression of IL-10 and TNF-α in mice with ischemia-reperfusion acute kidney injury

More Information
  • 摘要:   目的  探讨骨髓间充质干细胞(BMSC)对小鼠缺血-再灌注急性肾损伤(IR-AKI)过程中白细胞介素(IL)-10和肿瘤坏死因子(TNF)-α表达的影响。  方法  将小鼠随机分为假手术组(对照组)、缺血-再灌注损伤组(IRI组)和BMSC治疗组(BMSC组),每组6只。检测各组小鼠肾功能及病理学改变;检测各组小鼠肾组织细胞凋亡情况;检测各组小鼠血清IL-10和TNF-α的表达水平。将小鼠BMSC随机分为对照组和缺氧复氧组(IRI组),检测各组细胞上清IL-10和TNF-α的表达水平。  结果  对照组小鼠肾组织结构正常,IRI组肾组织结构损伤严重,BMSC组损伤较轻。与对照组比较,IRI组和BMSC组肾组织损伤评分较高;与IRI组比较,BMSC组小鼠肾组织损伤学评分较低(均为P < 0.05)。与对照组比较,IRI组小鼠血清肌酐(Scr)和血尿素氮(BUN)水平升高,BMSC组BUN水平升高;与IRI组比较,BMSC组小鼠Scr和BUN水平下降(均为P < 0.05)。IRI组肾组织凋亡细胞数量多于BMSC组和对照组,BMSC组凋亡细胞数量多于对照组(均为P < 0.05)。与对照组比较,IRI组小鼠血清IL-10和TNF-α水平均升高,BMSC组小鼠血清TNF-α水平下降,IL-10水平升高;与IRI组比较,BMSC组小鼠血清IL-10和TNF-α水平均下降(均为P < 0.05)。IRI组细胞上清IL-10、TNF-α水平与对照组比较,差异均无统计学意义(P=0.080、0.627)。  结论  BMSC输注可降低肾IRI及炎症反应,其机制可能是通过抑制TNF-α表达,而非促进IL-10的表达。

     

  • 图  1  各组小鼠肾组织病理学和肾功能变化

    注:A图为各组小鼠肾组织切片的病理学图片,黑色箭头表示肾小管扩张、坏死以及炎细胞浸润(HE,×200);B图为各组小鼠肾组织损伤评分;C图为IRI 72 h后各组小鼠Scr水平;D图为IRI 72 h后各组小鼠BUN水平;与对照组比较,aP < 0.05,与IRI组比较,bP < 0.05。

    Figure  1.  Changes in renal histopathology and renal function of mice in each group

    图  2  各组小鼠肾组织细胞凋亡情况(TUNEL,×400)

    Figure  2.  Cell apoptosis of renal tissues of mice in each group

    图  3  各组小鼠外周血IL-10和TNF-α的表达情况

    注:A图为各组小鼠外周血血清中IL-10的表达情况;B图为各组小鼠外周血血清中TNF-α的表达情况;与对照组比较,aP < 0.05,与IRI组比较,bP < 0.05。

    Figure  3.  The expression of IL-10 and TNF-α in peripheral blood of mice in each group

  • [1] 闫文娟. 急性肾损伤的研究进展[J]. 临床与病理杂志, 2019, 39(7): 1571-1575. DOI: 10.3978/j.issn.2095-6959.2019.07.032.

    YAN WJ. Research progress of acute kidney injury[J]. Int J Pathol Clin Med, 2019, 39(7): 1571-1575. DOI: 10.3978/j.issn.2095-6959.2019.07.032.
    [2] ZUK A, BONVENTRE JV. Acute kidney injury[J]. Annu Rev Med, 2016, 67: 293-307. DOI: 10.1146/annurev-med-050214-013407.
    [3] SKARUPSKIENĖ I, ADUKAUSKIENĖ D, KUZMINSKIENĖ J, et al. Mortality prediction in patients with acute kidney injury requiring renal replacement therapy after cardiac surgery[J]. Medicina (Kaunas), 2017, 53(4): 217-223. DOI: 10.1016/j.medici.2017.06.003.
    [4] 赵宏磊, 孙立忠. 主动脉外科手术后并发急性肾损伤的研究进展[J]. 中国医药, 2017, 12(9): 1423-1426. DOI: 10.3760/cma.j.issn.1673-4777.2017.09.039.

    ZHAO HL, SUN LZ. Research progress of acute kidney injury after aortic surgery[J]. Chin Med, 2017, 12(9): 1423-1426. DOI: 10.3760/cma.j.issn.1673-4777.2017.09.039.
    [5] 王延庆, 韩玉珍, 张进, 等. 肝移植术后血清肌红蛋白水平对患者新发急性肾损伤的预测价值[J]. 实用医学杂志, 2021, 37(1): 46-50. DOI: 10.3969/j.issn.1006-5725.2021.01.010.

    WANG YQ, HAN YZ, ZHANG J, et al. The predictive value of serum myoglobin level with the occurrence of acute renal injury in liver transplantation patients[J]. J Pract Med, 2021, 37(1): 46-50. DOI: 10.3969/j.issn.1006-5725.2021.01.010.
    [6] CAO Q, WANG R, WANG Y, et al. Regulatory innate lymphoid cells suppress innate immunity and reduce renal ischemia/reperfusion injury[J]. Kidney Int, 2020, 97(1): 130-142. DOI: 10.1016/j.kint.2019.07.019.
    [7] BONVENTRE JV, YANG L. Cellular pathophysiology of ischemic acute kidney injury[J]. J Clin Invest, 2011, 121(11): 4210-4221. DOI: 10.1172/JCI45161.
    [8] ZHENG L, GAO W, HU C, et al. Immune cells in ischemic acute kidney injury[J]. Curr Protein Pept Sci, 2019, 20(8): 770-776. DOI: 10.2174/1389203720666190507102529.
    [9] OUYANG W, O'GARRA A. IL-10 family cytokines IL-10 and IL-22: from basic science to clinical translation[J]. Immunity, 2019, 50(4): 871-891. DOI: 10.1016/j.immuni. 2019.03.020.
    [10] WAN X, HUANG WJ, CHEN W, et al. IL-10 deficiency increases renal ischemia-reperfusion injury[J]. Nephron Exp Nephrol, 2014, 128(1/2): 37-45. DOI: 10.1159/ 000366130.
    [11] GHOLAMPOUR F, ROOZBEH J, JANFESHAN S, et al. Remote ischemic per-conditioning protects against renal ischemia-reperfusion injury via suppressing gene expression of TLR4 and TNF-α in rat model[J]. Can J Physiol Pharmacol, 2019, 97(2): 112-119. DOI: 10.1139/cjpp-2018-0543.
    [12] HOU L, CHEN G, FENG B, et al. Small interfering RNA targeting TNF-α gene significantly attenuates renal ischemia-reperfusion injury in mice[J]. Curr Med Sci, 2016, 36(5): 634-638. DOI: 10.1007/s11596-016-1638-z.
    [13] HU H, ZOU C. Mesenchymal stem cells in renal ischemia-reperfusion injury: biological and therapeutic perspectives[J]. Curr Stem Cell Res Ther, 2017, 12(3): 183-187. DOI: 10.2174/1574888X11666161024143640.
    [14] 钱道海, 宋国栋, 张洲, 等. 骨髓间充质干细胞对重症急性胰腺炎胰腺组织修复的促进作用研究[J/CD]. 中华细胞与干细胞杂志(电子版), 2019, 9(6): 351-357. DOI: 10.3877/cma.j.issn.2095-1221.2019.06.006.

    QIAN DH, SONG GD, ZHANG Z, et al. Positive effect of bone marrow-derived mesenchymal stem cells on the repair of pancreatic tissue in severe acute pancreatitis[J/CD]. Chin J Cell Stem Cell (Electr Edit), 2019, 9(6): 351-357. DOI: 10.3877/cma.j.issn.2095-1221.2019.06.006.
    [15] 邢丽, 宋尔霖, 贾西贝, 等. 骨髓干细胞通过多种机制促进缺血再灌注小鼠肾脏修复[J]. 实用医学杂志, 2019, 35(7): 1073-1078. DOI: 10.3969/j.issn.1006-5725.2019.07.014.

    XING L, SONG EL, JIA XB, et al. Stem cells contribute to the regeneration of renal injury after ischemia-reperfusionth rough multiple mechanism[J]. J Pract Med, 2019, 35(7): 1073-1078. DOI: 10.3969/j.issn.1006-5725.2019.07.014.
    [16] AHMADI A, RAD NK, EZZATIZADEH V, et al. Kidney regeneration: stem cells as a new trend[J]. Curr Stem Cell Res Ther, 2020, 15(3): 263-283. DOI: 10.2174/1574888X15666191218094513.
    [17] TAMMARO A, KERS J, SCANTLEBERY AML, et al. Metabolic flexibility and innate immunity in renal ischemia reperfusion injury: the fine balance between adaptive repair and tissue degeneration[J]. Front Immunol, 2020, 11: 1346. DOI: 10.3389/fimmu.2020.01346.
    [18] DE WAAL MALEFYT R, ABRAMS J, BENNETT B, et al. Interleukin 10 (IL-10) inhibits cytokine synthesisby human monocytes: an autoregulatory role of IL-10produced by monocytes[J]. J Exp Med, 1991, 174(5): 1209-1220. DOI: 10.1084/jem.174.5.1209.
    [19] LI JH, TANG Y, LV J, et al. Macrophage migration inhibitory factor promotes renal injury induced by ischemic reperfusion[J]. J Cell Mol Med, 2019, 23(6): 3867-3877. DOI: 10.1111/jcmm.14234.
    [20] SAKAI K, NOZAKI Y, MURAO Y, et al. Protective effect and mechanism of IL-10 on renal ischemia-reperfusion injury[J]. Lab Invest, 2019, 99(5): 671-683. DOI: 10.1038/s41374-018-0162-0.
    [21] SHEN ZY, ZHANG J, SONG HL, et al. Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism[J]. World J Gastroenterol, 2013, 19(23): 3583-3595. DOI: 10.3748/wjg.v19.i23.3583.
    [22] YAN M, SHU S, GUO C, et al. Endoplasmic reticulum stress in ischemic and nephrotoxic acute kidney injury[J]. Ann Med, 2018, 50(5): 381-390. DOI: 10.1080/07853890.2018.1489142.
    [23] TEXTOR SC, ABUMOAWAD A, SAAD A, et al. Stem cell therapy for microvascular injury associated with ischemic nephropathy[J]. Cells, 2021, 10(4): 765. DOI: 10.3390/cells10040765.
    [24] CHANGIZI-ASHTIYANI S, HAFAZEH L, GHASEMI F, et al. The effect of adipose-derived mesenchymal stem cells on renal function and histopathology in a rat model of ischemia-reperfusion induced acute kidney injury[J]. Iran J Basic Med Sci, 2020, 23(8): 999-1006. DOI: 10.22038/ijbms.2020.40334.9601.
    [25] ZHANG ZY, HOU YP, ZOU XY, et al. Oct-4 enhanced the therapeutic effects of mesenchymal stem cell-derived extracellular vesicles in acute kidney injury[J]. Kidney Blood Press Res, 2020, 45(1): 95-108. DOI: 10.1159/000504368.
    [26] YANG Z, ZHANG XR, ZHAO Q, et al. Knockdown of TNF-α alleviates acute lung injury in rats with intestinal ischemia and reperfusion injury by upregulating IL-10 expression[J]. Int J Mol Med, 2018, 42(2): 926-934. DOI: 10.3892/ijmm.2018.3674.
    [27] WANG Z, GUAN D, HUO J, et al. IL-10 enhances human natural killer cell effector functions via metabolic reprogramming regulated by mTORC1 signaling[J]. Front Immunol, 2021, 12: 619195. DOI: 10.3389/fimmu. 2021.619195.
    [28] 石炳毅, 陈文, 刘志佳. 调节性免疫细胞在异种移植免疫中的作用[J]. 器官移植, 2020, 11(3): 321-325. DOI: 10.3969/j.issn.1674-7445.2020.03.001.

    SHI BY, CHEN W, LIU ZJ. The function of regulatory immunological cell in xenotransplantation immunity[J]. Organ Transplant, 2020, 11(3): 321-325. DOI: 10.3969/j.issn.1674-7445.2020.03.001.
    [29] JANG HR, RABB H. Immune cells in experimental acute kidney injury[J]. Nat Rev Nephrol, 2015, 11(2): 88-101. DOI: 10.1038/nrneph.2014.180.
    [30] PERICO N, CASIRAGHI F, REMUZZI G. Clinical translation of mesenchymal stromal cell therapies in nephrology[J]. J Am Soc Nephrol, 2018, 29(2): 362-375. DOI: 10.1681/ASN.2017070781.
    [31] TANG C, HAN H, LIU Z, et al. Activation of BNIP3-mediated mitophagy protects against renal ischemia-reperfusion injury[J]. Cell Death Dis, 2019, 10(9): 677. DOI: 10.1038/s41419-019-1899-0.
    [32] WANG Y, ZHU J, LIU Z, et al. The PINK1/PARK2/optineurin pathway of mitophagy is activated for protection in septic acute kidney injury[J]. Redox Biol, 2021, 38: 101767. DOI: 10.1016/j.redox.2020.101767.
    [33] CHEN ZD, HU BC, SHAO XP, et al. Ascorbate uptake enables tubular mitophagy to prevent septic AKI by PINK1-PARK2 axis[J]. Biochem Biophys Res Commun, 2021, 554: 158-165. DOI: 10.1016/j.bbrc.2021.03.103.
    [34] IP WKE, HOSHI N, SHOUVAL DS, et al. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages[J]. Science, 2017, 356(6337): 513-519. DOI: 10.1126/science.aal3535.
  • 加载中
图(4)
计量
  • 文章访问数:  61
  • HTML全文浏览量:  36
  • PDF下载量:  14
  • 被引次数: 0
出版历程
  • 收稿日期:  2021-06-22
  • 网络出版日期:  2021-09-15
  • 刊出日期:  2021-09-15

目录

    /

    返回文章
    返回