姜黄素后处理对大鼠肢体缺血再灌注肺损伤的影响  

Effect of curcumin-posttreatment during limb ischemia-reperfusion-induced lung injury in rats

作　　者：邹海波[1] 孙晓峰[1] ZOU Haibo;SUN Xiaofeng(Department of Anesthesiology,Affiliated Central Hospital,Shenyang Medical College,Shenyang 110024,China)

机构地区：[1]沈阳医学院附属中心医院麻醉科,辽宁沈阳110024

出　　处：《沈阳药科大学学报》2020年第8期707-711,共5页Journal of Shenyang Pharmaceutical University

基　　金：辽宁省教育厅一般项目(L2015540);沈阳医学院青年基金项目(20162029)。

摘　　要：目的探讨姜黄素后处理对大鼠肢体缺血再灌注肺损伤的影响。方法选取成年雄性SD大鼠60只,体质量280~320 g,6~8月龄,采用随机数字表法,将其分成3组(n=20):假手术组(Sham组)、缺血再灌注组(I/R组)、姜黄素(curcumin,Cur)后处理组(I/R+Cur组)。采用夹闭股动脉2 h再灌注3 h制备肢体缺血再灌注肺损伤模型。在大鼠肢体缺血后2 h,I/R+Cur组经腹腔注射姜黄素200 mg·kg^-1,其余各组以等量生理盐水替代。于再灌注3 h时经颈动脉取血,行动脉血气分析,随后处死大鼠,取肺组织采用HE染色检测病理变化、检测肺湿/干质量比(W/D)和肺组织损伤评分;应用Westen blot法和RT-PCR法分别测定Toll受体4(Toll-like receptors 4,TLR4)蛋白和NF-κB p65 mRNA的表达;采用ELISA法测定肺组织TNF-α及IL-1β的含量。结果与Sham组比较,I/R组HE染色切片可以看到肺泡内炎性介质浸润,肺泡膜增厚,肺间质充血水肿,视野内可见局限性肺不张等炎性改变,肺损伤评分和W/D升高,PaO2降低,同时TLR4蛋白和NF-κB p65 mRNA的表达以及TNF-α和IL-1β的含量升高(P<0.05);与I/R组比较,I/R+Cur组肺泡间质充血水肿和肺泡膜增厚程度减轻,炎性细胞减少,视野内未见肺不张等病理改变,同时,肺损伤评分和W/D降低,PaO2升高。TLR4蛋白和NF-κB p65 mRNA表达以及TNF-α和IL-1β含量下降(P<0.05)。结论姜黄素后处理可减轻大鼠肢体缺血再灌注时肺损伤,其作用机制可能与抑制TLR4/NF-κB信号通路,减少炎性因子TNF-α及IL-1β的释放有关,发挥肺保护作用。Objective To evaluate the effects of curcumin-posttreatment during the limb ischemia-reperfusioninduced lung injury in rats.Methods Sixty adult male Sprague-Dawley rats,aged 6-8 months,weighing 250-300 g,were randomly divided into 3 group(n=20)by using a random number table:sham operation group(group Sham),group I/R,group curcumin-posttreatment(group I/R+Cur).Limb ischemia was induced by occlusion of bilateral femoral arteries for 2 h followed by reperfusion for 3 h in I/R and I/R+Cur groups.At 2 h behind ischemia,curcumin 200 mg·kg^-1 was injected intraperitioneally in group I/R+Cur,while the equal volume of normal saline was given instead in the other groups.Arteries blood samples were taken at 3 h of reperfusion for blood gas analysis and PaO2 was recorded.The animals were then sacrificed and the lungs were removed immediately for HE staining,determination of lung wet/dry(W/D)ratio and lunginjury-score;separately determine the expression of Toll-like receptors 4(TLR4)and NF-κB p65 mRNA by westen-blot and RT-PCR in the lung tissue;determine TNF-αand IL-1βby ELISA in the lung tissue.Results Compared with group Sham,in the group I/R HE strainings showed that flammatory infiltration in the alveoluses,thickening alveolar membrane,pulmonary interstitial congestion-edema,localized pulmonary atelectasis and other inflammatory changes in the field of vision.Lung injury score and W/D increased.PaO2 was reduced.The expression of protein TLR4 and NF-κB p65 mRNA increased.And the release of TNF-αand IL-1βwere increased(P<0.05).Compared with group I/R,in the group I/R+Cur the pathological changes were alleviated.The degree of pulmonary interstitial congestion-edema and thickening of alveolar membrane reduced.The inflammatory cells decreased.No pulmonary atelectasis and other pathological changes in the field of vision.The expression of protein TLR4,NF-κB p65 mRNA,TNF-αand IL-1βwere lower(P<0.05).Conclusion Curcumin posttreatment can alleviate lung injury induced by limb ischemia-reperfusion in rats,and its protect

关 键 词：姜黄素 后处理 肢体 再灌注损伤 肺 

分 类 号：R94[医药卫生—药剂学]