期刊文献+

合成短肽S247对呼吸机所致肺损伤p38MAPK通路激活的影响 被引量:2

Effects of synthesized peptide S247 on the activation of p38MAPK during ventilator-induced lung injury
原文传递
导出
摘要 目的研究合成短肽S247对大鼠呼吸机所致肺损伤(VILI)p38MAPK通路激活的影响。方法30只健康雄性SD大鼠随机均分成A、B、C三组:A组潮气量(V_T)为8mL/kg,B组V_T为40 ml/kg,C组V_T为40mL/kg。试验前一周每天一次腹腔注射合成短肽S247溶液(100 mg/kg),直至试验前0.5h。各组通气时间均为2h,呼吸频率均为80次/min。试验结束处死大鼠,收集肺灌洗液和组织标本,光镜观察肺病理改变,Western Blot方法检测各组肺组织中p38、磷酸化p38(p-p38)的水平。同时分别检测各组肺灌洗液中总蛋白、白细胞计数、MPO以及MIP-2的水平。结果和A组相比,B组肺病理改变明显,总蛋白、白细胞计数、MPO、MIP-2、p-p38等指标均显著高于A组(P<0.01)。和B组相比,C组病理改变明显减轻,p-p38和其他各项指标指标均显著低于B组(P<0.01或P<0.05)。结论合成短肽S247能显著抑制VILI时p38通路的激活,减轻肺损伤,对VILI具有一定保护作用。 Objective To study the effect of synthesized peptide S247 on the activation of p38MAPK of ventilatorinduced lung injury. Methods Thirty healthy male SD rats were divided into group A, group B, group C, n 10. All rats were performed with mechanical ventilation, group A with tidal volume (VT) 8 ml/kg, breathing rate (p) 80/min; group B with tidal volume (VT) 40 ml/kg, breathing rate (p) = 80/min; group C with tidal volume (VT) 40 ml/kg, breathing rate (p) 80/min. The rats in group C were intraperitoneally injected with synthesized peptide S247 (100 mg/kg) once a day for a week. The time of ventilation in all groups was two hours. Rats were sacrificed after the experiment was finished. The lung lavage liquid and lung tissue were collected and stored with correct methods. The measured indexes included lung pathology change, total protein, WBC, MPO and MIP-2. The expression of p38 and p-p38 were measured by Western Blot in lung tissue. Results Compared with group A, total protein, WBC, MPO, MIP-2 and p-p38 significantly increased in group B; compared with group B, total protein, WBC, MPO, MIP-2 and p-p38 significantly decreased in group C. Conclusion Synthesized peptide S247 significantly inhibited the activation of p38 and relieved the degree of ventilator induced lung injury.
出处 《中华急诊医学杂志》 CAS CSCD 2006年第7期603-607,共5页 Chinese Journal of Emergency Medicine
基金 国家自然科学基金(30571787) 湖北省科技攻关计划项目(2005AA301C23)
关键词 呼吸机所致肺损伤 机械通气 整合素 Ventilator induced lung injury Mechanical ventilation Integrin
  • 相关文献

参考文献13

  • 1Liu MY,Tanswell AK,Post M.Mechanical force-induced signal transduction in lung cells[J].Am J Physiol,1999,277 (4):667 -683.
  • 2Li LF,Quyang B,Choukroun R,et al.Stretch-induced IL-8 depends on c-Jun NIt2-terminal and nuclear factor-κB-inducing kinases[J].Am J Physiol Lung Cell Mol Physiol,2003,285 (2):464-475.
  • 3Held HD,Boettcher S,Hamann L,et al.Ventilation-induced chemokine and cytokine release is associated with activation of nuclear factor-kappaB and is blocked by steroids[J].Am J Respir Crit Care Med,2001,163 (3):711-716.
  • 4Reinmuth N,Liu WB,Ahmad SA,et al.Integrin antagonist S247decreases colon cancer metastasis and angiogenesis and improves survival in mice[J].Cancer Research,2003,63 (9):2079-2087.
  • 5Nick JA,Young SK,Brown KK,et al.Role of p38 mitogen-activated protein kinase in a murine model of pulmonary inflanunation[J].J Imraunology,2000,164 (4):2151-2159.
  • 6Karzai W,Cui XZ,Heinicke N,et al.Neutrophil stimulation with granulocyte colonystimulating factor worsens ventilator-induced lung injury and mortality in rats[J].Anesthesiology,2005,103 (4):996-1005.
  • 7刘红岩.整合素激活FAK介导的信号传导途径研究进展[J].国外医学(免疫学分册),2000,23(1):1-5. 被引量:18
  • 8杨红军.整合素激活FAK介导的信号转导通路与大肠癌[J].国外医学(肿瘤学分册),2003,30(3):221-225. 被引量:9
  • 9Li CH,Xu QB.Mechanical stress-initiated signal transductions in vascular smooth muscle cells[J].Cellular Signalling,2000,12 (4):435-445.
  • 10Oktay M,Wary KK,Dans M,et al.Integrin-mediated activation of focal adhesion kinase is required for signaling to Jun NH2-terminal kinase and progression through the G1 phase of the cell cycle[J].J Cell Biol,1999,145 (7):1461-1469.

二级参考文献36

  • 1Kumar CC. Signaling by integrin receptors[J]. Oncogene, 1998, 17(11): 1365-1373.
  • 2de Melker AA, Sonnenberg A. Integrins: alternative splicing as a mechanism to regulate ligand binding and integrin signaling events[ J ]. Bioessays, 1999,21 ( 6 ) : 499-509.
  • 3Matter ML,Ruoslahti E. A signaling pathway from the alpha5betal and alpha(v) beta3 integrins that elevates bel-2 trartseription[J]. J Biol Chem, 2001,276(30) : 27757-27763.
  • 4Xie B, Zhao J, Kitagawa M, et al. Focal adhesion kinase activates Statl in integrin-mediated cell migration and adhesion[J]. J Biol Chem, 2001,276(22): 19512-19523.
  • 5Boudreau NJ, Jones PL. Extracellular matrix and integrin signaling: the shape of things to come[J]. Biochem J, 1999, 339(pt3):481-488.
  • 6Plow EF,Haas TA,Zhang L,et al. Ligand binding to integrins[J].J Biol Chem, 2000,275 (29) : 21785-21788.
  • 7Kim S, Harris M, Yarner JA. Regulation of integrin alpha(v)beta3-mediated endothelial cell migration and angiogenesis by integrin alpha5betal and protein kinase A[J]. J Biol Chem, 2000, 275(43) : 33920-33928.
  • 8Martin KH, Slack JK, Boerner SA, et al.Integrin connections map: to infinity and beyond[J]. Science,2002,296(5573): 1652-1653.
  • 9Barberis L, Wary KK, Fiucci G, et al. Distinct roles of the adaptor protein She and focal adhesion kinase in integrin signaling to ERK[J]. J Biol Chem, 2000, 275(47): 36532-36540.
  • 10Hecker TP, Grammer JR, Gillespie G, et al. Focal adhesion kinase enhances signaling through the Shc/extracellular signal-regulated kinase pathway in anaplastie astrocytoma tumor biopsy samples [J].Cancer Res, 2002,62 ( 9 ) : 2699-2707.

共引文献25

同被引文献23

  • 1Halbertsma FJ,Vaneker M,Scheffer CJ,et al.Cytokines and biotrau-ma in ventilator-induced lung injury:a critical review of the literature[J].Neth J Med,2005,63(10):382-392.
  • 2Ingber DE.Cellular mechanotransduction:putting all the pieces together again[J].FASEB J,2006,20(7):811-827.
  • 3Bogdan R,Veith C,Clause W,et al.Impact of mechanical stress on ion transport in native lung epithelium (Xenopus laevis):short-term activation of Na+,Cl-and K+ channels[J].Pflugers Arch,2008,456 (6):1109-1120.
  • 4Kanefsky J,Lenburg M,Hai CM.Cholinergic receptor and cyclic stretch-mediated inflammatory gene expression in intact ASM[J].Am J Respir Cell Mol Biol,2006,34(4):417-425.
  • 5Hamanaka K,Jian MY,Weber DS,et al.TRPV4 initiates the acute calcium-dependent permeability increase during ventilator-induced lung injury in isolated mouse lungs[J].Am J Physiol Lung Cell Mol Physiol,2007,293(4):L923-932.
  • 6Pahakis MY,Kosky JR,Dull RO,et al.The role of endothelial glyco-calyx components in mechanotransduction of fluid shear stress[J].Biochem Biophys Res Commun,2007,355(1):228-233.
  • 7Dull RO,Mecham I,McJames S.Heparan sulfates mediate pressure-induced increase in lung endothelial hydraulic conductivity via nitric oxide/reactive oxygen species[J].Am J Physiol Lung Cell Mol Physiol,2007,292(6):L1452-1458.
  • 8Budinger CR,Urich D,DeBiase PJ,et al.Stretch-induced activation of AMP kinase in the lung requires dystroglycan[J].Am J Respir Cell Mol Biol,2008,39(6):666-672.
  • 9Chaturvedi LS,Marsh HM,Basson MD.Src and focal adhesion kinase mediate mechanical strain-induced proliferation and KRK1/2 phospho-rylation in human H441 pulmonary epithelial cells[J].Am J Physiol Cell Physiol,2007,292(5):C1701-1713.
  • 10Thomas RA,Norman JC,Huynh TT,et al.Mechanical stretch has contrasting effects on mediator release from bronchial epithelial cells,with a rho-kinase-dependent component to the mechanotransduction pathway[J].Respir Med,2006,100(9):1588-1597.

引证文献2

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部