通腑平喘方对脓毒症急性肺损伤大鼠Keap1-Nrf2/ARE信号通路的影响Influence of Tongfu Pingchuan Decoction on Keap1-Nrf2/ARE Signaling Pathway in Rats with Sepsis-induced Acute Lung Injury
杨丽梦,熊旭东
摘要(Abstract):
目的观察通腑平喘方对脓毒症急性肺损伤大鼠核因子E2相关因子(Nrf2)表达的影响,探讨通腑平喘方对脓毒症急性肺损伤抗氧化应激的作用机制。方法采用CLP制作脓毒症模型,将40只成年雄性SD大鼠随机分为正常组、中药组、模型组及假手术组4组,每组10只。正常组于6 h、12 h后予以0.9%氯化钠注射液灌胃。假手术组开腹后将盲肠取出后再回纳到腹腔,术后6 h、12 h予以0.9%氯化钠注射液灌胃。模型组CLP术后立即予以0.9%氯化钠注射液灌胃,术后6 h、12 h予以0.9%氯化钠注射液灌胃。中药组CLP术后立即予以通腑平喘方灌胃,术后6 h、12 h再次予以通腑平喘方灌胃。以上各组均在24 h后麻醉并行腹主动脉采血致死,取出肺组织。术后观察大鼠一般情况,检测各组血清Nrf2、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、丙二醛(MDA)含量,RT-PCR法检测肺组织中Nrf2 m RNA表达量。结果中药组的血清Nrf2含量及Nrf2 mRNA表达水平高于模型组(P <0.01)。模型组大鼠血清MDA含量与正常组、假手术组及中药组相比明显升高(P <0.05),血清SOD含量及血清GSH含量与正常组、假手术组及中药组相比明显降低(P <0.05)。结论通腑平喘方对脓毒症急性肺损伤大鼠有保护作用,其机制可能与其激活Nrf2,上调SOD、GSH有关,起到抑制氧化应激反应、减轻肺组织损伤的作用。
关键词(KeyWords): 氧化应激;Nrf2;脓毒症;急性肺损伤
基金项目(Foundation): 上海市高等学校博士学科点专项科研基金项目(20113107110003)
作者(Author): 杨丽梦,熊旭东
参考文献(References):
- [1]Singer M,Dettschman CS,Seymour CW,et al.The third international consensus definitions for sepsis and septic shock(Sepsis-3)[J].JAMA,2016,315(8):801-810.
- [2]Esper AM,Martin GS.Extending international sepsis epidemiology:the impact of organ dysfunction[J].Critical Care,2009,13(1):120-122.
- [3]Huang Y,Pettitt SJ,Guo G,et al.Isolation of homozygous mutantmouse embryonic stem cells using a dual selection system[J].Nucleic Acids Res,2012,40(3):e21.
- [4]庄良明.桑白皮汤治疗脓毒症呼吸衰竭的临床疗效观察[J].中外医学研究,2015,13(29):46-48.
- [5]何淼,熊旭东,沈晓红.炎调方对脓毒症急性呼吸窘迫综合征(热炽营血证)患者血细胞因子的影响[J].中国中医急症,2013,22(7):1097-1099.
- [6]Sweatt AJ,Levitt JE.Evolving epidemiology and definitions of the acute respiratory distress syndrome and early acute lung injury[J].Clin Chest Med,2014(35):609-624.
- [7]Tsushima K,King LS,Aggarwal NR,et al.Acute lung injury review[J].Intern Med,2009(48):621-630.
- [8]Singh G,Gladdy G,Chandy TT,et al.Incidence and outcome of acute lung injury and acute respiratory distress syndrome in the surgical intensive care unit[J].Indian J Crit Care Med,2014(18):659-665.
- [9]Ward PA.Oxidative stress:acute and progressive lung injury[J].Ann N Y Acad Sci,2010(1203):53-59.
- [10]Shah NR,Iqbal MB,Barlow A,et al.Severe physical exertion,oxidative stress,and acute lung injury[J].Clin J Sport Med2011(21):537-538.
- [11]Shin MH,Moon YJ,Seo JE,et al.Reactive oxygen species produced by NADPH oxidase xanthine oxidase,and mitochondrial electron transport system mediate heat shockinduced MMP-1 and MMP-9 expression[J].Free RadicBio Med,2008,44(4):635-645.
- [12]Abreu CC,Cardozo L,Mafra D.Could physical exercises modulate Nrf2-Keap1 pathway in chronic kidney disease[J]Med Hypotheses,2015(84):44-46.
- [13]Devasagayam TP,Tilak JC,Boloor KK,et al.Free radicals and antioxidants in human health:current status and future prospects[J].J Assoc Physicians India,2004(52):794-804.
- [14]Ozben T.Oxidative stress and apoptosis:impact on cancer therapy[J].J Pharm Sci,2007(96):2181-2196.
- [15]Del RioD,Stewart AJ,Pellegrini N.A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress[J].Nutrition,Metabolism and Cardiovascular Diseases,2005,15(4):316-328.
- [16]Ji L,Liu R,Zhang XD,et al.N-acetylcysteine attenuates phosgene-496 induced acute lung injury via up-regulation of Nrf2 expression[J].Inhal Toxicol,2010,22(7):535-542.
- [17]赵京禹,费翔,岳琦,等.蛇床子素对脓毒症急性肺损伤大鼠的保护效应[J].中国医药导报,2013,10(28):103-106.
- [18]袁鼎山,李爱林,包玉华.还原型谷胱甘肽对脓毒症大鼠急性肺损伤的干预作用[J].中华危重症医学杂志,2013,6(6):353-358.