白藜芦醇减轻大鼠体外循环肺损伤的实验研究  

Resveratrol attenuate lung injury induced by cardiopulmonary bypass in rats

作　　者：刘小龙[1] 王常田[1] 黄海嵘[1] 吴海卫[1] 秦涛[1] 王高明[1] 李德闽[1] 

机构地区：[1]南京大学医学院临床学院(南京军区南京总医院)心胸外科,南京医学硕士研究生210002

出　　处：《医学研究生学报》2013年第3期244-247,共4页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81172032)

摘　　要：目的急性肺损伤是心脏体外循环(cardiopulmonary bypass,CPB)术后常见并发症之一,探寻新的治疗药物减轻CPB术后肺损伤是近年来的研究热点。文中研究白藜芦醇(resveratrol,RES)对于大鼠体外循环肺损伤的保护作用并探讨相关机制。方法雄性SD大鼠32只随机均分成4组(n=8):假手术组、对照(CPB)组、Vehicle组及RES组,经皮心脏不停跳大鼠体外循环模型建立后,收集不同时间点血样,并于术后12h获取大鼠肺组织和支气管肺泡灌洗液(bronchoalveolar lavagefluid,BALF),所有动物CPB术前5 d RES、载体或者等渗盐水腹腔注射。结果与假手术组相比,CPB后能够导致血浆、BALF及肺组织中肿瘤坏死因子-α(tumor necrosis factors-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)、基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)明显上升(P<0.05),然而RES预处理组能够明显减轻CPB导致的炎症指标的升高;与Vehicle组相比,RES明显降低CPB术后12 h肺组织磷酸化核因子κB抑制蛋白(phosphorylated inhibitor ofκBα,p-IκBα)表达(P<0.05)。组织病理学检查发现RES预处理组的中性粒细胞浸润、肺间质水肿、出血、透明膜形成和坏死等病理变化明显减轻。结论 RES可能通过抑制κB抑制蛋白(inhibitoryκB,IκB)的磷酸化,进而抑制核因子-κB(nuclear factor kappa B,NF-κB)的激活,进而下调TNF-α、IL-6、MMP-9等炎性因子的表达,显著减轻CPB术后肺损伤。Objective Acute lung injury is one of frequent complications after cardiopulmonary bypass （CPB） ,and search- ing for new therapeutic drugs to attenuate lung injury after CPB is a research hotspot in recent years. This experiment was designed to investigate the effect of pretreatment with resveratrol on CPB-induced lung jury and its mechanism. Methods Thirty two male SD rats were randomly divided into four groups of equal numbers ： sham, CPB, vehicle and resveratrol. The pereutaneous beating heart CPB model of rat was established. Blood were sampled at various time points, then lung tissues and bronchoalveolar lavage fluid were har- vested 12 h after CPB. Animals received resveratrol, vehicle or saline by intraperitoneal （IP） injection for 5 days before CPB. Results CPB induced a marked increase in the concentrations of interleukin-6, tumor necrosis factor-a,and matrix metalloproteinase- 9 in plasma, bronehoalveolar lavage fluid, and lung tissues （ P 〈 0.05 versus sham group）, whereas resveratrol pretreatment reduced these inflammatory markers compared with sham group. Resveratrol had effective inhibitory effects on the expi＇ession of p-IκBα in lung tissues 12 h post-CPB （P 〈 0.05 versus vehicle group）. Histologic findings indicated that resveratrol pretreatment markedly attenuated neutrophil infiltration,interstitial edema, hemorrhage, hyaline membrane formation, and necrosis. Conclusion RES may attenuate CPB-induced lung injury by suppressing the expression of inflammatory cytokines. This anti-inflammatory effect of resveratrol is partly related to the inhibition of IKB phosphorylation and thus inhibition of NF-κB activation.

关 键 词：白藜芦醇 体外循环 肺损伤 炎症因子 

分 类 号：R961.1[医药卫生—药理学]