右美托咪定对脓毒症大鼠肺组织髓样细胞触发受体-1表达的影响
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摘要
目的观察右美托咪定对脓毒症大鼠肺髓样细胞触发受体-1(Trem-1)表达的影响。方法将60只雄性SD大鼠随机分为假手术组(n=15)、脓毒症对照组(n=15)、脓毒症右美托咪定组(n=15)和脓毒症育亨宾+右美托咪定组(n=15)。通过盲肠结扎穿孔法(CLP)建立脓毒症模型,观察各组的24 h生存率;采用ELISA法测定血清白介素-6(Il-6)、肿瘤坏死因子-α(Tnf-α)和可溶性Trem-1(s Trem-1)浓度;观察肺组织病理变化并进行评分,通过real-time PCR和免疫组织化学法测定大鼠肺组织Trem-1的表达水平。结果与脓毒症对照组相比,右美托咪定组死亡率及血清Il-6、Tnf-α和s Trem-1浓度明显下降(P<0.05);肺组织炎症反应明显减轻(P<0.05);Trem-1的表达明显下降(P<0.05)。结论右美托咪定可通过抑制Trem-1的表达而减轻脓毒症大鼠肺部的炎症反应。
Objective To observe the effect of dexmedetomidine on the expression of triggering receptor expressed on myeloid cells-1(Trem-1) in lung tissues of rats with sepsis.Methods Sixty male Sprague Dawley(SD) rats were randomly divided into the sham group(n = 15),sepsis group(n = 15),dexmedetomidine group(n = 15),and yohimbine + dexmedetomidine group(n = 15).The sepsis model was established by cecal ligation and puncture(CLP).The survival rate of rats in 24 h was observed.Serum I1-6,Tnf-α,and sTrem-1 levels were measured by enzyme-linked immunosorbent assay(ELISA).The pathological changes of lung tissues were observed and scored.The expression of Trem-1 in lung tissues was detected by realtime PCR and immunohistochemichal method.Results Compared with the sepsis group,the mortality rate and serum I1-6,Tnf-α,and sTrem-1 levels of dexmedetomidine group remarkably decreased(P<0.05).The inflammatory response of lung tissue significantly alleviated(P<0.05) and the expression of Trem-1 remarkably decreased(P<0.05).Conclusion Dexmedetomidine can alleviate the inflammatory response of lung tissues of rats with sepsis by inhibiting the expression of Trem-1.
Objective To observe the effect of dexmedetomidine on the expression of triggering receptor expressed on myeloid cells-1(Trem-1) in lung tissues of rats with sepsis.Methods Sixty male Sprague Dawley(SD) rats were randomly divided into the sham group(n = 15),sepsis group(n = 15),dexmedetomidine group(n = 15),and yohimbine + dexmedetomidine group(n = 15).The sepsis model was established by cecal ligation and puncture(CLP).The survival rate of rats in 24 h was observed.Serum I1-6,Tnf-α,and sTrem-1 levels were measured by enzyme-linked immunosorbent assay(ELISA).The pathological changes of lung tissues were observed and scored.The expression of Trem-1 in lung tissues was detected by realtime PCR and immunohistochemichal method.Results Compared with the sepsis group,the mortality rate and serum I1-6,Tnf-α,and sTrem-1 levels of dexmedetomidine group remarkably decreased(P<0.05).The inflammatory response of lung tissue significantly alleviated(P<0.05) and the expression of Trem-1 remarkably decreased(P<0.05).Conclusion Dexmedetomidine can alleviate the inflammatory response of lung tissues of rats with sepsis by inhibiting the expression of Trem-1.
引文
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[12]Srivastava VK,Agrawal S,Kumar S,et al.Comparison of dexmedetomidine,propofol and midazolam for short-term sedation in postoperatively mechanically ventilated neurosurgical patients[J].J Clin Diagn Res,2014,8(9):GC04-GC07.
[13]Genua M,Rutella S,Correale C,et al.The triggering receptor expressed on myeloid cells(trem)in inflammatory bowel disease pathogenesis[J].J Transl Med,2014,12(1):293.
[14]Straub RH,Herrmann M,Berkmiller G,et al.Neuronal regulation of interleukin 6 secretion in murine spleen:Adrenergic and opioidergic control[J].J Neurochem,1997,68(4):1633-1639.
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[16]Yang CL,Chen CH,Tsai PS,et al.Protective effects of dexmedetomidine-ketamine combination against ventilator-induced lung injury in endotoxemia rats[J].J Surg Res,2011,167(2):e273-e281.
[17]Hanci V,Yurdakan G,Yurtlu S,et al.Protective effect of dexmedetomidine in a rat model of alpha-naphthylthiourea-induced acute lung injury[J].J Surg Res,2012,178(1):424-430.
[18]Colonna M,Facchetti F.Trem-1(triggering receptor expressed on myeloid cells):A new player in acute inflammatory responses[J].J Infect Dis,2003,187(Suppl 2):S397-S401.
[19]Prufer S,Weber M,Sasca D,et al.Distinct signaling cascades of trem-1,tlr and nlr in neutrophils and monocytic cells[J].J Innate Immun,2014,6(3):339-352.
[20]Bouchon A,Dietrich J,Colonna M.Cutting edge:inflammatory responses can be triggered by trem-1,a novel receptor expressed on neutrophils and monocytes[J].J Immunol,2000,164(10):4991-4995.
[21]Gomez-Pina V,Soares-Schanoski A,Rodriguez-Rojas A,et al.Metalloproteinases shed trem-1 ectodomain from lipopolysaccharidestimulated human monocytes[J].J immunol,2007,179(6):4065-4073.
[22]Dimopoulou I,Pelekanou A,Mavrou I,et al.Early serum levels of soluble triggering receptor expressed on myeloid cells-1 in septic patients:Correlation with monocyte gene expression[J].J Crit Care,2012,27(3):294-300.
[23]Schenk M,Bouchon A,Seibold F,et al.Trem-1-expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases[J].J Clin Invest,2007,117(10):3097-3106.
[24]Gibot S,Massin F,Marcou M,et al.Trem-1 promotes survival during septic shock in mice[J].Eur J Immunol,2007,37(2):456-466.
[25]Martin-Gonzlez F,Gonz lez-Robledo J,S nchez-Hern ndez F,et al.Effectiveness and predictors of failure of noninvasive mechanical ventilation in acute respiratory failure[J].Med Intensiva,2015,[Epub ahead of print].
[26]Jiang L,Li L,Shen J,et al.Effect of dexmedetomidine on lung ischemiareperfusion injury[J].Mol Med Rep,2014,9(2):419-426.
[27]Palazzo SJ,Simpson T,Schnapp LM.Triggering receptor expressed on myeloid cells type 1 as a potential therapeutic target in sepsis[J].Dimens Crit Care Nurs,2012,31(1):1-6.
[2]Casey LC,Balk RA,Bone RC.Plasma cytokine and endotoxin levels correlate with survival in patients with the sepsis syndrome[J].Ann Intern Med,1993,119(8):771-778.
[3]Marty C,Misset B,Tamion F,et al.Circulating interleukin-8concentrations in patients with multiple organ failure of septic and nonseptic origin[J].Crit Care Med,1994,22(4):673-679.
[4]Damas P,Reuter A,Gysen P,et al.Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans[J].Crit Care Med,1989,17(10):975-978.
[5]Tessarz AS,Cerwenka A.The trem-1/dap12 pathway[J].Immunol Lett,2008,116(2):111-116.
[6]Coursin DB,Coursin DB,Maccioli GA.Dexmedetomidine[J].Curr Opin Crit Care,2001,7(4):221-226.
[7]Taniguchi T,Kurita A,Kobayashi K,et al.Dose-and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats[J].J Anesth,2008,22(3):221-228.
[8]Rittirsch D,Huber-Lang MS,Flierl MA,et al.Immunodesign of experimental sepsis by cecal ligation and puncture[J].Nat Protoc,2009,4(1):31-36.
[9]Yang CH,Tsai PS,Wang TY,et al.Dexmedetomidine-ketamine combination mitigates acute lung injury in haemorrhagic shock rats[J].Resuscitation,2009,80(10):1204-1210.
[10]Xie C,Wang Z,Tang J,et al.The effect of dexmedetomidine posttreatment on the inflammatory response of astrocyte induced by lipopolysaccharide[J].Cell Biochem Biophys,2015,71(1):407-412.
[11]刘海林,钱燕宁.右美托咪定对心脏瓣膜置换术患者围术期炎性反应的影响[J].中国应用生理学杂志,2013,29(4):316-317.
[12]Srivastava VK,Agrawal S,Kumar S,et al.Comparison of dexmedetomidine,propofol and midazolam for short-term sedation in postoperatively mechanically ventilated neurosurgical patients[J].J Clin Diagn Res,2014,8(9):GC04-GC07.
[13]Genua M,Rutella S,Correale C,et al.The triggering receptor expressed on myeloid cells(trem)in inflammatory bowel disease pathogenesis[J].J Transl Med,2014,12(1):293.
[14]Straub RH,Herrmann M,Berkmiller G,et al.Neuronal regulation of interleukin 6 secretion in murine spleen:Adrenergic and opioidergic control[J].J Neurochem,1997,68(4):1633-1639.
[15]Walboomers F,Paquay YC,Jansen JA.A new titanium fiber meshcuffed peritoneal dialysis catheter:evaluation and comparison with a dacron-cuffed tenckhoff catheter in goats[J].Perit Dial Int,2001,21(3):254-262.
[16]Yang CL,Chen CH,Tsai PS,et al.Protective effects of dexmedetomidine-ketamine combination against ventilator-induced lung injury in endotoxemia rats[J].J Surg Res,2011,167(2):e273-e281.
[17]Hanci V,Yurdakan G,Yurtlu S,et al.Protective effect of dexmedetomidine in a rat model of alpha-naphthylthiourea-induced acute lung injury[J].J Surg Res,2012,178(1):424-430.
[18]Colonna M,Facchetti F.Trem-1(triggering receptor expressed on myeloid cells):A new player in acute inflammatory responses[J].J Infect Dis,2003,187(Suppl 2):S397-S401.
[19]Prufer S,Weber M,Sasca D,et al.Distinct signaling cascades of trem-1,tlr and nlr in neutrophils and monocytic cells[J].J Innate Immun,2014,6(3):339-352.
[20]Bouchon A,Dietrich J,Colonna M.Cutting edge:inflammatory responses can be triggered by trem-1,a novel receptor expressed on neutrophils and monocytes[J].J Immunol,2000,164(10):4991-4995.
[21]Gomez-Pina V,Soares-Schanoski A,Rodriguez-Rojas A,et al.Metalloproteinases shed trem-1 ectodomain from lipopolysaccharidestimulated human monocytes[J].J immunol,2007,179(6):4065-4073.
[22]Dimopoulou I,Pelekanou A,Mavrou I,et al.Early serum levels of soluble triggering receptor expressed on myeloid cells-1 in septic patients:Correlation with monocyte gene expression[J].J Crit Care,2012,27(3):294-300.
[23]Schenk M,Bouchon A,Seibold F,et al.Trem-1-expressing intestinal macrophages crucially amplify chronic inflammation in experimental colitis and inflammatory bowel diseases[J].J Clin Invest,2007,117(10):3097-3106.
[24]Gibot S,Massin F,Marcou M,et al.Trem-1 promotes survival during septic shock in mice[J].Eur J Immunol,2007,37(2):456-466.
[25]Martin-Gonzlez F,Gonz lez-Robledo J,S nchez-Hern ndez F,et al.Effectiveness and predictors of failure of noninvasive mechanical ventilation in acute respiratory failure[J].Med Intensiva,2015,[Epub ahead of print].
[26]Jiang L,Li L,Shen J,et al.Effect of dexmedetomidine on lung ischemiareperfusion injury[J].Mol Med Rep,2014,9(2):419-426.
[27]Palazzo SJ,Simpson T,Schnapp LM.Triggering receptor expressed on myeloid cells type 1 as a potential therapeutic target in sepsis[J].Dimens Crit Care Nurs,2012,31(1):1-6.