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蛋白激酶C β抑制剂对肾缺血-再灌注损伤模型及其巨噬细胞亚型表达的影响

樊雪梅 容松

樊雪梅, 容松. 蛋白激酶C β抑制剂对肾缺血-再灌注损伤模型及其巨噬细胞亚型表达的影响[J]. 器官移植, 2019, 10(4): 423-428. doi: 10.3969/j.issn.1674-7445.2019.04.012
引用本文: 樊雪梅, 容松. 蛋白激酶C β抑制剂对肾缺血-再灌注损伤模型及其巨噬细胞亚型表达的影响[J]. 器官移植, 2019, 10(4): 423-428. doi: 10.3969/j.issn.1674-7445.2019.04.012
Fan Xuemei, Rong Song. Effect of protein kinase C β inhibitor on renal ischemia-reperfusion injury and expression level of macrophage subtypes in rat models[J]. ORGAN TRANSPLANTATION, 2019, 10(4): 423-428. doi: 10.3969/j.issn.1674-7445.2019.04.012
Citation: Fan Xuemei, Rong Song. Effect of protein kinase C β inhibitor on renal ischemia-reperfusion injury and expression level of macrophage subtypes in rat models[J]. ORGAN TRANSPLANTATION, 2019, 10(4): 423-428. doi: 10.3969/j.issn.1674-7445.2019.04.012

蛋白激酶C β抑制剂对肾缺血-再灌注损伤模型及其巨噬细胞亚型表达的影响

doi: 10.3969/j.issn.1674-7445.2019.04.012
基金项目: 

国家自然科学基金 81260056

详细信息
    作者简介:

    樊雪梅,女,1991年生,硕士研究生,研究方向为器官移植,Email:826245519@qq.com

    通讯作者:

    容松,男,1965年生,博士研究生导师,研究方向为器官移植,Email:1409843531@qq.com

  • 中图分类号: R617

Effect of protein kinase C β inhibitor on renal ischemia-reperfusion injury and expression level of macrophage subtypes in rat models

More Information
  • 摘要:   目的  探讨蛋白激酶C(PKC)β抑制剂对大鼠肾缺血-再灌注损伤(RIRI)模型的影响并检测巨噬细胞亚型的表达情况。  方法  健康SD雄性大鼠18只,按照随机数字表法分为假手术组(Sham组)、RIRI组、PKCβ抑制剂+RIRI组(Inhibitor+RIRI组),每组6只。术后24 h取血清、左肾组织标本,用全自动生化仪检测血清肌酐(Scr)、血尿素氮(BUN)含量,苏木素-伊红(HE)染色观察肾组织内炎症细胞浸润和病理损伤情况,用免疫组织化学法和Western Blot法检测各组大鼠肾组织CD68、诱生型一氧化氮合酶(iNOS)及CD206蛋白表达情况。  结果  RIRI组大鼠血清Scr、BUN含量明显高于Sham组(均为P < 0.05),Inhibitor+RIRI组大鼠血清Scr、BUN含量明显低于RIRI组(均为P < 0.05)。Sham组肾脏无明显损伤,RIRI组肾脏炎症细胞浸润及肾小管结构损伤明显,Inhibitor +RIRI组肾脏炎症细胞浸润及肾小管结构损伤轻于RIRI组。RIRI组大鼠肾组织中CD68、iNOS及CD206的蛋白表达量均明显高于Sham组(均为P < 0.05);Inhibitor+RIRI组CD68、iNOS的蛋白表达量均明显低于RIRI组(均为P < 0.05);Inhibitor+RIRI组CD206的蛋白表达量明显高于RIRI组(P < 0.05)。  结论  PKCβ抑制剂可在一定程度上减轻大鼠RIRI,这可能与PKCβ抑制剂改善缺血肾组织中炎症细胞浸润、促进巨噬细胞向M2表达有关。

     

  • 图  1  各组大鼠的肾组织损伤及炎症细胞浸润情况(HE, ×400)

    A图为Sham组;B图为RIRI组;C图为Inhibitor+RIRI组

    Figure  1.  Renal tissue damage and inflammatory cell infiltration in each group of rats

    图  2  各组大鼠肾组织CD68、iNOS及CD206的免疫组化图片(免疫组化,×400)

    A、D、G图为Sham组;B、E、H图为RIRI组;C、F、I图为Inhibitor+RIRI组

    Figure  2.  Immunohistochemical images of CD68, iNOS and CD206 in renal tissue among each group of rats

    图  3  各组大鼠肾组织CD68、iNOS及CD206蛋白的表达情况

    与Sham组比较,aP < 0.05;与RIRI组比较,bP < 0.05

    Figure  3.  Expression of CD68, iNOS and CD206 protein in renal tissue among each group of rats

  • [1] CHOUCHANI ET, PELL VR, JAMES AM, et al.A unifying mechanism for mitochondrial superoxide production during ischemia-reperfusion injury[J]. Cell Metab, 2016, 23(2):254-263. DOI: 10.1016/j.cmet.2015.12.009.
    [2] ELTZSCHIG HK, ECKLE T. Ischemia and reperfusion--from mechanism to translation[J]. Nat Med, 2011, 17(11):1391-1401. DOI: 10.1038/nm.2507.
    [3] JAESCHKE H, WOOLBRIGHT BL. Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species[J]. Transplant Rev (Orlando), 2012, 26(2):103-114. DOI: 10.1016/j.trre.2011.10.006.
    [4] HAUSENLOY DJ, BOSTON-GRIFFITHS E, YELLON DM. Cardioprotection during cardiac surgery[J]. Cardiovasc Res, 2012, 94(2):253-265. DOI: 10.1093/cvr/cvs131.
    [5] KARUPPAGOUNDER V, BAJPAI A, MENG S, et al. Small molecule disruption of G protein βγ subunit signaling reprograms human macrophage phenotype and prevents autoimmune myocarditis in rats[J]. PLoS One, 2018, 13(7):e0200697. DOI: 10.1371/journal.pone.0200697.
    [6] CHEN J, LI M, YANG C, et al. Macrophage phenotype switch by sequential action of immunomodulatory cytokines from hydrogel layers on titania nanotubes[J]. Colloids Surf B Biointerfaces, 2018, 163:336-345. DOI: 10.1016/j.colsurfb.2018.01.007.
    [7] CHEN S, LI R, CHENG C, et al. Pseudomonas aeruginosa infection alters the macrophage phenotype switching process during wound healing in diabetic mice[J]. Cell Biol Int, 2018, 42(7):877-889. DOI: 10.1002/cbin.10955.
    [8] 李春燕. PKCβ抑制剂对大鼠肾脏缺血再灌注损伤后M1及M2型巨噬细胞浸润的影响[D].遵义: 遵义医学院, 2017. http://cpfd.cnki.com.cn/Article/CPFDTOTAL-GZKX201811001100.htm
    [9] 肖婷.肾缺血再灌注损伤中蛋白激酶C对巨噬细胞的影响[J].海南医学, 2017, 27(8):1302-1305.DOI: 10.3969/j.issn.1003-6350.2017.08.034.

    XIAO T. Influence of protein kinase C on macrophages in renal ischemia-reperfusion injury[J]. Hainan Med J, 2017, 27(8):1302-1305. DOI: 10.3969/j.issn.1003-6350.2017.08.034.
    [10] YONA S, KIM KW, WOLF Y, et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis[J]. Immunity, 2013, 38(1):79-91. DOI: 10.1016/j.immuni.2012.12.001.
    [11] MALYSHEV I, MALYSHEV Y. Current concept and update of the macrophage plasticity concept: intracellular mechanisms of reprogramming and M3 macrophage "switch" phenotype[J]. Biomed Res Int, 2015:341308. DOI: 10.1155/2015/341308.
    [12] SUN YY, LI XF, MENG XM, et al. Macrophage phenotype in liver injury and repair[J]. Scand J Immunol, 2017, 85(3):166-174. DOI: 10.1111/sji.12468.
    [13] BUDHIRAJA S, SINGH J. Protein kinase C beta inhibitors: a new therapeutic target for diabetic nephropathy and vascular complications[J]. Fundam Clin Pharmacol, 2008, 22(3):231-240. DOI: 10.1111/j.1472-8206.2008.00583.x.
    [14] NOH H, KING GL. The role of protein kinase C activation in diabetic nephropathy[J]. Kidney Int Suppl, 2007, 106:S49-S53.DOI: 10.1038/sj.ki.5002386.
    [15] 柯贵宝.蛋白激酶C-β抑制剂对大鼠移植肾脏的影响[D].遵义: 遵义医学院, 2013. http://d.wanfangdata.com.cn/Thesis/Y2341118
    [16] 杨旸, 杨亦彬, 梁国标, 等.蛋白激酶C抑制剂对小鼠肾移植后炎性细胞浸润的影响[J].中华实验外科杂志, 2015, 32(1):204.DOI: 10.3760/cma.j.issn.1001-9030.2015.01.086.

    YANG Y, YANG YB, LIANG GB, et al. Effect of protein kinase C inhibitor on inflammatory cell infiltration after renal transplantation in mice[J].Chin J Exp Surg, 2015, 32(1):204. DOI: 10.3760/cma.j.issn.1001-9030.2015.01.086.
    [17] TSENG HC, KANAYAMA K, KAUR K, et al. Erratum: bisphosphonate-induced differential modulation of immune cell function in gingiva and bone marrow in vivo: role in osteoclast-mediated NK cell activation[J]. Oncotarget, 2015, 6(38):41398. DOI: 10.18632/oncotarget.6431.
    [18] CHO KY, MIYOSHI H, KURODA S, et al. The phenotype of infiltrating macrophages influences arteriosclerotic plaque vulnerability in the carotid artery[J]. J Stroke Cerebrovasc Dis, 2013, 22(7):910-918. DOI: 10.1016/j.jstrokecerebrovasdis.2012.11.020.
    [19] HUEN SC, HUYNH L, MARLIER A, et al. GM-CSF promotes macrophage alternative activation after renal ischemia/reperfusion injury[J]. J Am Soc Nephrol, 2015, 26(6):1334-1345. DOI: 10.1681/ASN.2014060612.
    [20] CURTIS BJ, BOE DM, SHULTS JA, et al. Effects of multi-day ethanol intoxication on post-burn inflammation, lung function, and alveolar macrophage phenotype[J]. Shock, 2018, 51(5):625-633. DOI: 10.1097/SHK.0000000000001188.
    [21] BONITO V, SMITS AIPM, GOOR OJGM, et al. Modulation of macrophage phenotype and protein secretion via heparin-IL-4 functionalized supramolecular elastomers[J]. Acta Biomater, 2018, 71:247-260. DOI: 10.1016/j.actbio.2018.02.032.
    [22] 胡林昆, 陈城, 王卫珍, 等.抑炎因子IL-35与移植肾功能延迟恢复关系的研究[J].器官移植, 2018, 9(4):272-277.DOI: 10.3969/j.issn.1674-7445.2018.04.006.

    HU LK. CHEN C, WANG WZ, et al. Study on the relationship between anti-inflammatory cytokine IL-35and delayed renal graft function[J]. Organ Transplant, 2018, 9(4):272-277.DOI: 10.3969/j.issn.1674-7445.2018.04.006.
    [23] 方羚, 陈晨, 康新梅, 等.小鼠脑实质注射水通道蛋白4抗体所致的病理损伤[J].中山大学学报(医学科学版), 2018, 39(2):207-214, 244. http://d.old.wanfangdata.com.cn/Periodical/zsykdxxb201802007

    FANG L, CHEN C, KANG XM, et al. Lesions caused by intracerebral injection of aquaporin-4 immunoglobulin G[J]. J Sun Yat-sen Univ(Med Sci), 2018, 39(2):207-214, 244. http://d.old.wanfangdata.com.cn/Periodical/zsykdxxb201802007
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出版历程
  • 收稿日期:  2019-04-10
  • 网络出版日期:  2021-01-19
  • 刊出日期:  2019-07-15

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