低剂量促红细胞生成素对大鼠肾移植物急性炎症反应的影响
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摘要
目的探讨促红细胞生成素(EPO)对大鼠肾移植物急性炎症反应的影响及可能机制。方法建立单侧大鼠同系基因肾移植模型,随机分为假手术组、肾移植模型组、EPO给药组。PAS染色观察肾脏病理学变化,免疫组织化学检测移植肾组织中单核/巨噬细胞表面标志物(ED)-1、诱导型一氧化氮合成酶(i NOS)、半胱氨酸-天冬氨酸蛋白酶(Caspase)-3表达水平。结果与肾移植模型组相比,EPO给药组急性炎症反应明显减轻,肾组织病理学损伤明显改善,ED-1、i NOS、Caspase-3的表达水平也明显减低。结论 EPO可通过减轻大鼠肾移植后炎症细胞浸润、细胞因子释放,抗氧化、抑制凋亡等作用,减轻大鼠肾移植后的急性炎症反应,从而保护肾移植后肾移植物的功能。
Objective To study the effect and possible mechanism of low dose erythropoietin on acute inflammation of kidney transplant in rat models.Methods The model was established by unilateral isogenic renal transplantation in rat. These rats were randomly divided into sham-operated,isogenic renal transplantation control,and erythropoietin treatment groups. The morphological changes were observed by PAS staining. The expressions of ED-1,i NOS and Caspase-3 in the kidney were assessed by immunohistochemistry methods or Western blot.Results Compared with those of control group,the acute inflammation was significantly reduced in erythropoietin treatment group,the pathological changes of renal were significantly improved,the levels of ED-1,i NOS and Caspase-3 were significantly reduced. Conclusions Erythropoietin may reduce acute inflammation through reducing inflammatory cells infiltration and cytokine release,anti-oxidation,anti-apoptotic,thereby protect the renal function of the isograft after transplantation.
Objective To study the effect and possible mechanism of low dose erythropoietin on acute inflammation of kidney transplant in rat models.Methods The model was established by unilateral isogenic renal transplantation in rat. These rats were randomly divided into sham-operated,isogenic renal transplantation control,and erythropoietin treatment groups. The morphological changes were observed by PAS staining. The expressions of ED-1,i NOS and Caspase-3 in the kidney were assessed by immunohistochemistry methods or Western blot.Results Compared with those of control group,the acute inflammation was significantly reduced in erythropoietin treatment group,the pathological changes of renal were significantly improved,the levels of ED-1,i NOS and Caspase-3 were significantly reduced. Conclusions Erythropoietin may reduce acute inflammation through reducing inflammatory cells infiltration and cytokine release,anti-oxidation,anti-apoptotic,thereby protect the renal function of the isograft after transplantation.
引文
1 Mehta R,Bhusal S,Randhawa P,et al.Short-term adverse effects of early subclinical allograft inflammation in kidney transplant recipients with a rapid steroid withdrawal protocol[J].Am J Transplant,2018:18(7):1710-7.
2 Liu Y,Shi BX,Li Y,et al.Protective effect of luteolin against renal ischemia/reperfusion injury via modulation of pro-inflammatory cytokines,oxidative stress and apoptosis for possible beneft in kidney transplant[J].Med Sci Monit,2017;23(12):5720-7.
3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.
4姜洋,梁贵友,胡婷婷,等.促红细胞生成素下肢缺血后血管再生的机制研究[J].中华实验外科杂志,2013;30(11):2456.
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6陈亚楠,容松.免疫反应在肾缺血/再灌注损伤中的研究进展[J].医学综述,2016;22(5):851-4.
7 Wystrychowski G,Wystrychowski W,Grzeszczak W,et al.Pentoxifylline and methylprednisolone additively alleviate kidney failure and prolong survival of rats after renal warm ischemia-reperfusion[J].Int JMol Sci,2018;19(1):1-11.
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11 Cao X,Xia HY,Zhang T,et al.Protective effect of lyophilized recombinant human brain natriuretic peptide on renal ischemia/reperfusion injury in mice[J].Genet Mol Res,2015;14(4):13300-11.
12 Hosgood SA,Yates PJ,Nicholson ML.1400W reduces ischemia reperfusion injury in an ex-vivo porcine model of the donation after circulatory death kidney donor[J].Word J Transplat,2014;4(4):299-305.
13 Kezic A,Stajic N,Thaiss F,et al.Innate immune response in kidney ischemia/reperfusion injury:potential target for therapy[J].J Immunol Res,2017;2017(6):1-10.
14 Xu YM,Ding GH,Huang J,et al.TanshinoneⅡA pretreatment attenuates ischemia/reperfusion-induced renal injury[J].Exp Ther Med,2016;12(4):2741-6.
15 Abogresha1 NM,Greish SM,Abdelaziz EZ,et al.Remote effect of kidney ischemia-reperfusion injury on pancreas:role of oxidative stress and mitochondrial apoptosis[J].Arch Med Sci,2016;12(2):252-62.
16 Lee JH,Kam EH,Kim SY,et al.Erythropoietin attenuates postoperative cognitive dysfunction by shifting macrophage activation toward the M2 phenotype[J].Front Pharmacol,2017;8(11):1-5.
17 Banaei S,Ahmadiasl N,Alihemmati A.Comparison of the protective effects of erythropoietin and melatonin on renal ischemia-reperfusion injury[J].Trauma Mon,2016;21(3):e23005.
18 Jiang CJ,Wang ZJ,Zhao YJ,et al.Erythropoietin reduces apoptosis of brain tissue cells in rats after cerebral ischemia/reperfusion injury:a characteristic analysis using magnetic resonance imaging[J].Neural Regen Res,2016;11(9):1450-5.
19 Rong R,Xiao XJ.Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury[J].Exp Ther Med,2015;10(2):413-8.
20 Zhang JH,Zhao DQ,Na N,et al.Renoprotective effect of erythropoietin via modulation of the STAT6/MAPK/NF-κB pathway in ischemia/reperfusion injury after renal transplantation[J].Int J Mol Med,2018;41(1):25-32.
21谭州科,杨亦彬,于泓,等.促红细胞生成素通过减少炎性细胞迁移减轻肾间质纤维化[J].中华实验外科杂志,2011;28(12):2080-2.
2 Liu Y,Shi BX,Li Y,et al.Protective effect of luteolin against renal ischemia/reperfusion injury via modulation of pro-inflammatory cytokines,oxidative stress and apoptosis for possible beneft in kidney transplant[J].Med Sci Monit,2017;23(12):5720-7.
3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.
4姜洋,梁贵友,胡婷婷,等.促红细胞生成素下肢缺血后血管再生的机制研究[J].中华实验外科杂志,2013;30(11):2456.
5 Mc Dougall ARA,Hale N,Rees S,et al.Erythropoietin protects against lipopolysaccharide-induced microgliosis and abnormal granule cell development in the ovine fetal cerebellum[J].Front Cell Neurosci,2017;11(7):1-10.
6陈亚楠,容松.免疫反应在肾缺血/再灌注损伤中的研究进展[J].医学综述,2016;22(5):851-4.
7 Wystrychowski G,Wystrychowski W,Grzeszczak W,et al.Pentoxifylline and methylprednisolone additively alleviate kidney failure and prolong survival of rats after renal warm ischemia-reperfusion[J].Int JMol Sci,2018;19(1):1-11.
8 Fontana J,Vogt A,Hohenstein A,et al.Impact of Steroids on the inflammatory response after ischemic acute kidney injury in rats[J].Indian J Nephrol,2017;27(5):365-71.
9 Hulya O,Cetinkaya A,Yilmaz F,et al.Protective effect of oxymatrine against renal ischemia/reperfusion injury in rats[J].Bratisl Lek Listy,2017;118(4):217-22.
10 Shen B,Liu J,Zhang F,et al.CCR2 positive exosome released by mesenchymal stem cells suppresses macrophage functions and alleviates ischemia/reperfusion-induced renal injury[J].Stem Cells Int,2016;2016(10):1-9.
11 Cao X,Xia HY,Zhang T,et al.Protective effect of lyophilized recombinant human brain natriuretic peptide on renal ischemia/reperfusion injury in mice[J].Genet Mol Res,2015;14(4):13300-11.
12 Hosgood SA,Yates PJ,Nicholson ML.1400W reduces ischemia reperfusion injury in an ex-vivo porcine model of the donation after circulatory death kidney donor[J].Word J Transplat,2014;4(4):299-305.
13 Kezic A,Stajic N,Thaiss F,et al.Innate immune response in kidney ischemia/reperfusion injury:potential target for therapy[J].J Immunol Res,2017;2017(6):1-10.
14 Xu YM,Ding GH,Huang J,et al.TanshinoneⅡA pretreatment attenuates ischemia/reperfusion-induced renal injury[J].Exp Ther Med,2016;12(4):2741-6.
15 Abogresha1 NM,Greish SM,Abdelaziz EZ,et al.Remote effect of kidney ischemia-reperfusion injury on pancreas:role of oxidative stress and mitochondrial apoptosis[J].Arch Med Sci,2016;12(2):252-62.
16 Lee JH,Kam EH,Kim SY,et al.Erythropoietin attenuates postoperative cognitive dysfunction by shifting macrophage activation toward the M2 phenotype[J].Front Pharmacol,2017;8(11):1-5.
17 Banaei S,Ahmadiasl N,Alihemmati A.Comparison of the protective effects of erythropoietin and melatonin on renal ischemia-reperfusion injury[J].Trauma Mon,2016;21(3):e23005.
18 Jiang CJ,Wang ZJ,Zhao YJ,et al.Erythropoietin reduces apoptosis of brain tissue cells in rats after cerebral ischemia/reperfusion injury:a characteristic analysis using magnetic resonance imaging[J].Neural Regen Res,2016;11(9):1450-5.
19 Rong R,Xiao XJ.Erythropoietin pretreatment suppresses inflammation by activating the PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury[J].Exp Ther Med,2015;10(2):413-8.
20 Zhang JH,Zhao DQ,Na N,et al.Renoprotective effect of erythropoietin via modulation of the STAT6/MAPK/NF-κB pathway in ischemia/reperfusion injury after renal transplantation[J].Int J Mol Med,2018;41(1):25-32.
21谭州科,杨亦彬,于泓,等.促红细胞生成素通过减少炎性细胞迁移减轻肾间质纤维化[J].中华实验外科杂志,2011;28(12):2080-2.