间充质干细胞治疗脓毒症研究进展
摘要
<正>脓毒症是感染引起的全身炎症反应综合征(systemic inflammatory response syndrome,SIRS),是临床常见的危重病症~([1]),由脓毒症引起的院内病死率为29.3%~30.9%,是临床危重症患者的主要死亡原因之一~([2-3])。发达国家脓毒症在ICU患者中的发病率为6%~30%[4],进一步进展可出现脓毒性休克、多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)。常规的脓毒症治疗方
引文
[1]Jawad I,Luksic I,Rafnsson S B.Assessing available information on the burden of sepsis:global estimates of incidence,prevalence and mortality[J].J Global Health,2012,2(1):010404.
[2]Fujishima S,Gando S,Saitoh D,et al.A multicenter,prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines[J].J Infect Chemother,2014,20(2):115-120.
[3]Czupryna P,Garkowski A,Moniuszko A,et al.Patients with sepsis in infectious diseases department in years1997—2010-epidemiology and clinical features[J].Przegl Epidemiol,2013,67(3):429-434,535-538.
[4]Vincent J L,Sakr Y,Sprung C L,et al.Sepsis in european intensive care units:results of the soap study[J].Crit Care Med,2006,34(2):344-353.
[5]常欣欣,赵丽琪,张津,等.间充质干细胞在脓毒治疗中的新进展[J].世界最新医学信息文摘,2016,16(35):48-49.
[6]Tsiotou A G,Sakorafas G H,Anagnstopodos G,et al.Septic shock:carrent pathogenetic concepts from a clinical perspecttve[J].Med Sci Monit,2005,1(3):76-85.
[7]Liu J,Xiang J,Li X,et al.NF-kappa B activation is critical for bacterial lipoprotein tolerance-enhanced bactericidal activity in macrophages during microbial infection[J].Sci Rep,2017,7:40418.
[8]Hui L,Yao Y,Wang S,et al.Inhibition of janus kinase2 and signal transduction and activator of transcription 3protect against cecal ligation and puncture-induced multiple organ damage and mortality[J].J Trauma,2009,66(3):859-865.
[9]Manukyan M C,Weil B R,Wang Y,et al.The phosphoinositide-3 kinase survival signaling mechanism in sepsis[J].Shock,2010,34(5):442-449.
[10]张泽信,王晓霞,杨湾湾,等.脓毒症分子机制及miRNA在脓毒症中的作用[J].现代生物医学进展,2014,14(22):4377-4381.
[11]陈偲,杨敬平.Toll样受体4与髓样细胞触发受体1在脓毒症的诊断中研究现状[J].中国医疗前沿,2013,8(3):14-16.
[12]崔萍,程宝莉,方向明.脓毒症的生物标记物[J].创伤外科杂志,2014,16(6):561-564.
[13]Rhodes A,Evans L E,Alhazzani W,et al.Surviving Sepsis Campaign:International Guidelines for Management of Sepsis and Septic Shock:2016[J].Intensive Care Med,2017,43(3):304-377.
[14]Seymour C W,Liu V X,Iwashyna T J,et al.Assessment of Clinical Criteria for Sepsis:For the Third International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3)[J].JAMA,2016,315(8):762-774.
[15]Luo C J,Zhang F J,Zhang L,et al.Mesenchymal stem cells ameliorate sepsis-associated acute kidney injury in mice[J].Shock,2014,41(2):123-129.
[16]Lombardo E,van der Poll T,DelaRosa O,et al.Mesenchymal stem cells as a therapeutic tool to treat sepsis[J].World J Stem Cells,2015,7(2):368-379.
[17]滕金龙,李丹,于海初,等.重组人促红细胞生成素联合骨髓间充质干细胞移植治疗脓毒症大鼠心肌损伤[J].中国组织工程研究,2014,18(28):4530-4534.
[18]Quevedo H C,Hatzistergos K E,Oskouei B N,et al.Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy VIA trilineage differentiating capacity[J].Proc Natl Acad Sci U S A,2009,106(33):14022-14027.
[19]Meadow W L,Rudinsky B F,Strates E,et al.Oxygen delivery,oxygen consumption,and metabolic acidosis during group B streptococcal sepsis in piglets[J].Pediatric research,1987,22:509-512.
[20]Zarbock A,Gomez H,Kellum J A.Sepsis-induced acute kidney injury revisited:pathophysiology,prevention and future therapies[J].Curr Opin Crit Care,2014,20(6):588-595.
[21]Li G,Jia J,Ji K,et al.The neutrophil elastase inhibitor,sivelestat,attenuates sepsis-related kidney injury in rats[J].Int J Mol Med,2016,38(3):767-775.
[22]Gilbert E M,Haupt M T,Mandanas R Y,et al.The effect of fluid loading,blood transfusion,and catecholamine infusion on oxygen delivery and consumption in patients with sepsis[J].Am Rev Respir Dis,1986,134(5):873-878.
[23]李娜,胡大海,王耀军,等.脂肪间充质干细胞对烧伤脓毒症小鼠肾脏损伤的作用[J].中华烧伤杂志,2013,29(3):249-254.
[24]徐大莉,杨莉.脓毒症相关急性肾损伤[J].中国实用内科杂志,2016,36(6):441-444.
[25]Hegyi B,Kudlik G,Monostori E,et al.Activated T-cells and pro-inflammatory cytokines differentially regulate prostaglandin E2secretion by mesenchymal stem cells[J].Biochem Biophys Res Commun,2012,419(2):215-220.
[26]Yi T,Lee D S,Jeon M S,et al.Gene expression profile reveals that stat2 is involved in the immunosuppressive function of human bone marrow-derived mesenchymal stem cells[J].Gene,2012,497(2):131-139.
[27]Teo G S,Ankrum J A,Martinelli R,et al.Mesenchymal stem cells transmigrate between and directly through tumor necrosis factor-alpha-activated endothelial cells via both leukocyte-like and novel mechanisms[J].Stem Cells,2012,30(11):2472-2486.
[28]熊丽红,郑晓英,陈伟峰,等.脓毒症患者并发急性肺损伤危险因素分析[J].实用医学杂志,2011,27(8):1401-1403.
[29]孙萌,井丽娟.E选择素与急性肺损伤[J].国际儿科学杂志,2007,34(2):93-95.
[30]占利民,方林森,胡德林,等.脓毒症相关性急性肺损伤发病机制研究进展[J].安徽医药,2010,14(6):722-723.
[31]赵尚平,肖雪飞,欧好,等.骨髓间充质干细胞对脓毒症小鼠急性肺损伤的影响[J].中国急救医学,2015,35(11):973-976,插2.
[32]Johnson B L,Goetzman H S,Prakash P S,et al.Mechanisms underlying mouse TNF-alpha stimulated neutrophil derived microparticle generation[J].Biochem Biophys Res Commun,2013,437(4):591-596.
[33]Gao S,Mao F,Zhang B,et al.Mouse bone marrow-derived mesenchymal stem cells induce macrophage M2 polarization through the nuclear factor-kappa B and signal transducer and activator of transcription 3 pathways[J].Exp Biol Med(Maywood),2014,239(3):366-375.
[34]陈肖,梁欢,连洁,等.骨髓间充质干细胞对创伤弧菌脓毒症肺损伤的保护作用[J].中华危重病急救医学,2014,26(11):821-826.
[35]张继峰,张紫琦,雒晓田,等.骨髓间充质干细胞对脓毒症急性肺损伤大鼠肺泡巨噬细胞NF-κB的调控[J].中国组织工程研究,2015,19(10):1556-1561.
[36]Nieuwenhuijzen G A,Deitch E A,Goris R J.The relationship between gut-derived bacteria and the development of the multiple organ dysfunction syndrome[J].J Anat,1996,189(Pt 3)N:537-548.
[37]陈晓明,朱娱,郑丹阳,等.聚肌苷酸胞苷酸增强间充质干细胞对脓毒症大鼠肠屏障功能的保护作用[J].第三军医大学学报,2016,38(9):959-963.
[38]Zhang W,Shen Z Y,Song H L,et al.Protective effect of bone marrow mesenchymal stem cells in intestinal barrier permeability after heterotopic intestinal transplantation[J].World J Gastroenterol,2014,20(23):7442-7451.
[39]李亚红.乳酸清除率对脓毒性休克早期液体复苏治疗的指导价值[J/CD].中华临床医师杂志:电子版,2012,6:5354-5355.
[40]Chen H,Min X H,Wang Q Y,et al.Pre-activation of mesenchymal stem cells with TNF-alpha,IL-1beta and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury[J].Sci Rep,2015,5:8718.
[41]Nemeth K,Leelahavanichkul A,Yuen P S,et al.Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production[J].Nat Med,2009,15(1):42-49.
[42]Sepulveda J C,Tome M,Fernandez M E,et al.Cell senescence abrogates the therapeutic potential of human mesenchymal stem cells in the lethal endotoxemia model[J].Stem Cells,2014,32(7):1865-1877.
[43]Pedrazza L,Lunardelli A,Luft C,et al.Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model[J].Inflamm Res,2014,63(9):719-728.
[2]Fujishima S,Gando S,Saitoh D,et al.A multicenter,prospective evaluation of quality of care and mortality in Japan based on the Surviving Sepsis Campaign guidelines[J].J Infect Chemother,2014,20(2):115-120.
[3]Czupryna P,Garkowski A,Moniuszko A,et al.Patients with sepsis in infectious diseases department in years1997—2010-epidemiology and clinical features[J].Przegl Epidemiol,2013,67(3):429-434,535-538.
[4]Vincent J L,Sakr Y,Sprung C L,et al.Sepsis in european intensive care units:results of the soap study[J].Crit Care Med,2006,34(2):344-353.
[5]常欣欣,赵丽琪,张津,等.间充质干细胞在脓毒治疗中的新进展[J].世界最新医学信息文摘,2016,16(35):48-49.
[6]Tsiotou A G,Sakorafas G H,Anagnstopodos G,et al.Septic shock:carrent pathogenetic concepts from a clinical perspecttve[J].Med Sci Monit,2005,1(3):76-85.
[7]Liu J,Xiang J,Li X,et al.NF-kappa B activation is critical for bacterial lipoprotein tolerance-enhanced bactericidal activity in macrophages during microbial infection[J].Sci Rep,2017,7:40418.
[8]Hui L,Yao Y,Wang S,et al.Inhibition of janus kinase2 and signal transduction and activator of transcription 3protect against cecal ligation and puncture-induced multiple organ damage and mortality[J].J Trauma,2009,66(3):859-865.
[9]Manukyan M C,Weil B R,Wang Y,et al.The phosphoinositide-3 kinase survival signaling mechanism in sepsis[J].Shock,2010,34(5):442-449.
[10]张泽信,王晓霞,杨湾湾,等.脓毒症分子机制及miRNA在脓毒症中的作用[J].现代生物医学进展,2014,14(22):4377-4381.
[11]陈偲,杨敬平.Toll样受体4与髓样细胞触发受体1在脓毒症的诊断中研究现状[J].中国医疗前沿,2013,8(3):14-16.
[12]崔萍,程宝莉,方向明.脓毒症的生物标记物[J].创伤外科杂志,2014,16(6):561-564.
[13]Rhodes A,Evans L E,Alhazzani W,et al.Surviving Sepsis Campaign:International Guidelines for Management of Sepsis and Septic Shock:2016[J].Intensive Care Med,2017,43(3):304-377.
[14]Seymour C W,Liu V X,Iwashyna T J,et al.Assessment of Clinical Criteria for Sepsis:For the Third International Consensus Definitions for Sepsis and Septic Shock(Sepsis-3)[J].JAMA,2016,315(8):762-774.
[15]Luo C J,Zhang F J,Zhang L,et al.Mesenchymal stem cells ameliorate sepsis-associated acute kidney injury in mice[J].Shock,2014,41(2):123-129.
[16]Lombardo E,van der Poll T,DelaRosa O,et al.Mesenchymal stem cells as a therapeutic tool to treat sepsis[J].World J Stem Cells,2015,7(2):368-379.
[17]滕金龙,李丹,于海初,等.重组人促红细胞生成素联合骨髓间充质干细胞移植治疗脓毒症大鼠心肌损伤[J].中国组织工程研究,2014,18(28):4530-4534.
[18]Quevedo H C,Hatzistergos K E,Oskouei B N,et al.Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy VIA trilineage differentiating capacity[J].Proc Natl Acad Sci U S A,2009,106(33):14022-14027.
[19]Meadow W L,Rudinsky B F,Strates E,et al.Oxygen delivery,oxygen consumption,and metabolic acidosis during group B streptococcal sepsis in piglets[J].Pediatric research,1987,22:509-512.
[20]Zarbock A,Gomez H,Kellum J A.Sepsis-induced acute kidney injury revisited:pathophysiology,prevention and future therapies[J].Curr Opin Crit Care,2014,20(6):588-595.
[21]Li G,Jia J,Ji K,et al.The neutrophil elastase inhibitor,sivelestat,attenuates sepsis-related kidney injury in rats[J].Int J Mol Med,2016,38(3):767-775.
[22]Gilbert E M,Haupt M T,Mandanas R Y,et al.The effect of fluid loading,blood transfusion,and catecholamine infusion on oxygen delivery and consumption in patients with sepsis[J].Am Rev Respir Dis,1986,134(5):873-878.
[23]李娜,胡大海,王耀军,等.脂肪间充质干细胞对烧伤脓毒症小鼠肾脏损伤的作用[J].中华烧伤杂志,2013,29(3):249-254.
[24]徐大莉,杨莉.脓毒症相关急性肾损伤[J].中国实用内科杂志,2016,36(6):441-444.
[25]Hegyi B,Kudlik G,Monostori E,et al.Activated T-cells and pro-inflammatory cytokines differentially regulate prostaglandin E2secretion by mesenchymal stem cells[J].Biochem Biophys Res Commun,2012,419(2):215-220.
[26]Yi T,Lee D S,Jeon M S,et al.Gene expression profile reveals that stat2 is involved in the immunosuppressive function of human bone marrow-derived mesenchymal stem cells[J].Gene,2012,497(2):131-139.
[27]Teo G S,Ankrum J A,Martinelli R,et al.Mesenchymal stem cells transmigrate between and directly through tumor necrosis factor-alpha-activated endothelial cells via both leukocyte-like and novel mechanisms[J].Stem Cells,2012,30(11):2472-2486.
[28]熊丽红,郑晓英,陈伟峰,等.脓毒症患者并发急性肺损伤危险因素分析[J].实用医学杂志,2011,27(8):1401-1403.
[29]孙萌,井丽娟.E选择素与急性肺损伤[J].国际儿科学杂志,2007,34(2):93-95.
[30]占利民,方林森,胡德林,等.脓毒症相关性急性肺损伤发病机制研究进展[J].安徽医药,2010,14(6):722-723.
[31]赵尚平,肖雪飞,欧好,等.骨髓间充质干细胞对脓毒症小鼠急性肺损伤的影响[J].中国急救医学,2015,35(11):973-976,插2.
[32]Johnson B L,Goetzman H S,Prakash P S,et al.Mechanisms underlying mouse TNF-alpha stimulated neutrophil derived microparticle generation[J].Biochem Biophys Res Commun,2013,437(4):591-596.
[33]Gao S,Mao F,Zhang B,et al.Mouse bone marrow-derived mesenchymal stem cells induce macrophage M2 polarization through the nuclear factor-kappa B and signal transducer and activator of transcription 3 pathways[J].Exp Biol Med(Maywood),2014,239(3):366-375.
[34]陈肖,梁欢,连洁,等.骨髓间充质干细胞对创伤弧菌脓毒症肺损伤的保护作用[J].中华危重病急救医学,2014,26(11):821-826.
[35]张继峰,张紫琦,雒晓田,等.骨髓间充质干细胞对脓毒症急性肺损伤大鼠肺泡巨噬细胞NF-κB的调控[J].中国组织工程研究,2015,19(10):1556-1561.
[36]Nieuwenhuijzen G A,Deitch E A,Goris R J.The relationship between gut-derived bacteria and the development of the multiple organ dysfunction syndrome[J].J Anat,1996,189(Pt 3)N:537-548.
[37]陈晓明,朱娱,郑丹阳,等.聚肌苷酸胞苷酸增强间充质干细胞对脓毒症大鼠肠屏障功能的保护作用[J].第三军医大学学报,2016,38(9):959-963.
[38]Zhang W,Shen Z Y,Song H L,et al.Protective effect of bone marrow mesenchymal stem cells in intestinal barrier permeability after heterotopic intestinal transplantation[J].World J Gastroenterol,2014,20(23):7442-7451.
[39]李亚红.乳酸清除率对脓毒性休克早期液体复苏治疗的指导价值[J/CD].中华临床医师杂志:电子版,2012,6:5354-5355.
[40]Chen H,Min X H,Wang Q Y,et al.Pre-activation of mesenchymal stem cells with TNF-alpha,IL-1beta and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury[J].Sci Rep,2015,5:8718.
[41]Nemeth K,Leelahavanichkul A,Yuen P S,et al.Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production[J].Nat Med,2009,15(1):42-49.
[42]Sepulveda J C,Tome M,Fernandez M E,et al.Cell senescence abrogates the therapeutic potential of human mesenchymal stem cells in the lethal endotoxemia model[J].Stem Cells,2014,32(7):1865-1877.
[43]Pedrazza L,Lunardelli A,Luft C,et al.Mesenchymal stem cells decrease splenocytes apoptosis in a sepsis experimental model[J].Inflamm Res,2014,63(9):719-728.