外源性瘦素预防糖尿病大鼠呼吸机相关性肺损伤机制探讨
摘要
目的探讨外源性瘦素对糖尿病大鼠呼吸机相关性肺损伤(VILI)的保护机制。方法选择Wistar大鼠40只,取其中30只制备2型糖尿病模型并分为B、C、D组各10只,其余10只未造模大鼠为A组。造模后各组腹腔注射麻醉,气管切开并插管,A、B组带管自主呼吸,C组应用40 m L/kg潮气量行呼吸机机械通气4 h,D组经气管插管滴注外源性重组瘦素50μg/kg后,应用40 m L/kg潮气量行呼吸机机械通气4 h。机械通气结束后,处死各组大鼠,取出肺脏,测定湿干比(W/D),HE染色法观察肺组织病理改变并进行病理评分,免疫组化法检测肺组织瘦素及瘦素受体(OB-Rb)蛋白表达,ELISA法检测肺组织匀浆中白细胞介素1β(IL-1β)、髓过氧化物酶(MPO)、巨噬细胞炎症蛋白2(MIP-2)及肿瘤坏死因子α(TNF-α)水平。结果 C、D组W/D、肺组织病理评分均高于A、B组,D组W/D、肺组织病理评分、瘦素、OB-Rb蛋白表达均低于C组(P均<0.05)。D组肺组织匀浆中IL-1β、TNF-α、MIP-2、MPO水平及肺组织瘦素、OB-Rb表达均低于C组(P均<0.05)。结论外源性瘦素预处理可明显减轻糖尿病大鼠VILI,其机制可能与抑制内源性瘦素水平及肺组织炎症反应有关。
引文
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[13]穆维新,沈亚欣,崔士杰,等.2型糖尿病大鼠肺组织基质金属蛋白酶-2、9及其抑制因子-1的表达变化[J].河北医药,2010,32(9):1034-1037.
[14]Pastor CM,Rubbia BL,Hadengue A,et al.Role of macrophage inflammatory peptide-2 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury[J].Lab Invest,2003,83(4):471-478.
[15]Haegens A,Heeringa P,van Suylen RJ,et al.Myeloperoxidase deficiency attenuates lipopolysaccharide-induced acute lung inflammation and subsequent cytokine and chemokine production[J].J Immun,2009,182(12):7990-7996.
[2]杨海涛,田亚强,张光珍.2型糖尿病患者肺功能改变及其相关因素分析[J].山东医药,2006,46(32):39-40.
[3]Hou N,Luo JD.Leptin and cardiovascular diseases[J].Bri J Dia Vasc Dis,2011,38(12):905-913.
[4]姚艳敏,王希柱,宋巧凤,等.外源性瘦素在急性肺栓塞合并肺损伤中的作用机制研究[J].中华全科医学,2013,11(2):171-174.
[5]Ismail TA,Soliman MM,Nassan MA.Molecular and immunohistochemical effects of metformin in a rat model of type 2 diabetes mellitus[J].Exp Ther Med,2015,9(5):1921-1930.
[6]武庆平,刘萍,王立奎,等.不同潮气量通气对大鼠呼吸机相关性肺损伤模型的影响[J].华中科技大学学报(医学版),2006,35(4):511-514.
[7]Pastor CM,Rubbia-Brandt L,Hadengue A,et al.Role of macrophage inflammatory peptide-2 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury[J].Lab Invest,2003,83(4):471-478.
[8]周峥,曾军,肖正华,等.2型糖尿病对肺功能的影响[J].中国煤炭工业医学杂志,2005,8(6):566-567.
[9]孙建勋,王静.2型糖尿病患者肺功能变化及其影响因素[J].中国医药导报,2006,3(30):22-24.
[10]Bhattacharya S,Sen N,Yiming MT,et al.High tidal volume ventilation induces proinflammatory signaling in rat lung endothelium[J].Am J Respir Cell Mol Biol,2003,28(2):218-224.
[11]Zarkesh-Esfahani H,Pockley G,Metcalfe RA,et al.High-dose Leptin activates human leukocytes via receptor expression on monocytes[J].J Immun,2001,167(8):4593-4599.
[12]余帆,徐彤彤,吕祥威,等.瘦素预处理对2型糖尿病大鼠心肌缺血再灌注损伤的保护作用[J].吉林大学学报(医学版),2013,39(6):1219-1223.
[13]穆维新,沈亚欣,崔士杰,等.2型糖尿病大鼠肺组织基质金属蛋白酶-2、9及其抑制因子-1的表达变化[J].河北医药,2010,32(9):1034-1037.
[14]Pastor CM,Rubbia BL,Hadengue A,et al.Role of macrophage inflammatory peptide-2 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury[J].Lab Invest,2003,83(4):471-478.
[15]Haegens A,Heeringa P,van Suylen RJ,et al.Myeloperoxidase deficiency attenuates lipopolysaccharide-induced acute lung inflammation and subsequent cytokine and chemokine production[J].J Immun,2009,182(12):7990-7996.