白细胞介素-17A在小鼠机械通气相关性肺损伤中的作用

目的探讨白细胞介素-17A(IL-17A)在小鼠机械通气相关性肺损伤中的作用。方法SPF级雄性C57BL/6小鼠40只,2～3月龄,体重25～30 g。将小鼠随机分为四组:假手术组(S组),假手术+IL-17A单克隆抗体组(SA组),机械通气肺损伤模型组(V组),机械通气损伤模型+IL-17A单克隆抗体组(VA组),每组10只。S组和SA组仅行气管切开保留自主呼吸。V组和VA组机械通气4 h。SA组和VA组在气管切开后于腹腔注射IL-17A单克隆抗体(10μg, 0.1 ml),S组和V组于腹腔注射等体积的抗体稀释液。机械通气结束时处死小鼠取肺组织,采用ELISA法检测支气管肺泡灌洗液(BALF)中肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)浓度,测定肺组织湿干重比值(W/D),采用TUNEL染色法测定肺组织细胞凋亡指数,采用Western Blot法检测肺组织IL-17A和cleaved-caspase-3蛋白含量,采用HE染色法观察肺组织病理学结果并进行肺损伤评分。结果与S组比较,V组和VA组BALF中TNF-α和IL-6浓度、W/D、细胞凋亡指数、肺组织IL-17A和cleaved-caspase-3蛋白含量、肺损伤评分均明显升高(P0.05),肺组织病理学改变加重。与V组比较,VA组BALF中TNF-α和IL-6浓度、W/D、细胞凋亡指数、肺组织IL-17A和cleaved-caspase-3蛋白含量、肺损伤评分均明显降低(P0.05),肺组织病理学损伤改善。S组和SA组各项指标差异无统计学意义。结论大潮气量机械通气可导致机械通气相关性肺损伤,IL-17A介导了机械通气相关性肺损伤的发生、发展过程,可能与IL-17A加重炎症反应和诱导细胞凋亡有关。阻断IL-17A可通过减轻肺组织炎症反应、减少细胞凋亡改善机械通气相关性肺损伤。     

慢病毒介导的RNA干扰对小鼠胰腺星状细胞中半乳糖凝集素-1基因沉默效应的研究

目的:评价慢病毒介导的RNA干扰技术对小鼠胰腺星状细胞(mPSC)中半乳糖凝集素-1(galectin-1)基因的沉默效应,并观察其对mPSC增殖的影响。方法:设计并合成3条galectin-1基因特异性RNAi靶序列,构建到慢病毒PLKO.1-PURO载体中。从慢病毒包装转染的293T细胞,获得病毒上清感染的mPSC;采用嘌呤霉素(2μg/μL)筛选出慢病毒感染成功的mPSC。实时荧光定量RT-PCR和Western印迹法检测mPSC中galectin-1 mRNA和蛋白的表达,MTT法检测mPSC的增值能力。结果:PCR扩增和测序表明成功构建galectin-1慢病毒干扰载体,可以有效沉默mPSC中galectin-1基因的表达。构建的RNAi慢病毒载体感染mPSC后galectin-1 mRNA表达量同对照组比较,分别为(19.4±4.8)%、(6.2±4.3)%、(27.6±5.7)%,galectin-1蛋白表达量同对照组比较分别为(25.9±3.6)%、(10.8±4.1)%、(30.2±3.2)%。稳定的galectin-1沉默mPSC在第4天细胞增殖能力下降(22.9±2.7)%(P     

细胞间粘附分子-l在机械通气致肺损伤中的作用

目的 探讨细胞间粘附分子－１（ＩＣＡＭ－１）在机械通气致肺损伤中的作用。方法 ２４只普通健康小猪随机等分为对照组、低潮气量组（Ａ组）、正常潮气量组（Ｂ组）及大潮气量组（Ｃ组）。采用持续给予小猪不同潮气量通气模型,利用免疫组织化学技术、酶联免疫法和髓过氧化物酶（ＭＰＯ）测定法,分别检测不同潮气量组通气１ｄ、３ｄ、７ｄ后肺血管内皮细胞表面ＩＣＡＭ－１的表达量,血清和肺组织匀浆中肿瘤坏死因子α（ＴＮＦ－     

Caspase-1选择性抑制剂VX-765在大鼠急性肾损伤相关性肺损伤中的作用

目的 评价caspase-1选择性抑制剂VX-765在大鼠急性肾损伤(AKI)相关性肺损伤中的作用.方法 SPF级SD雄性大鼠72只,9～10周龄,体重350～400 g.采用随机数字表法分为四组:假手术组(S组)、AKI组(A组)、DMSO+AKI组(D组)和VX-765+AKI组(V组),每组18只.S组暴露双肾4...     

半乳糖凝集素-3与肾脏疾病的关系

目前已有许多研究显示半乳糖凝集素家族中的半乳糖凝集素-3参与多种疾病病理生理过程,其在肾脏病中承担角色的研究已有诸多进展,值得学界关注。本篇将对半乳糖凝集素-3在肾脏表达、慢性肾脏病、急性肾损伤和肾移植中的潜在作用进行综述。     

机械通气肺损伤的基本机制

机械通气肺损伤发生机制复杂,临床表现多样,日益受到重视.其基本机制为对肺组织过度牵拉的机械因素和机械力学诱导的肺脏局部细胞因子和炎症介质的释放.不适当的机械通气除可造成气压损伤、容积损伤和肺不张损伤等机械性损伤外,其最后的共同途径可能是激活细胞内信号转导通路和加重炎症介质介导的肺局部炎症反应,即机械伤转化为生物伤.现就其发生机制、防治对策等方面的研究作一简要综述.     

不同剂量瘦素对大鼠机械通气肺损伤的影响

目的评价不同剂量瘦素对大鼠机械通气肺损伤的影响。方法健康清洁级SD雄性大鼠48只,6～8周龄,采用随机数字表法分为四组:气管切开保留自主呼吸的假手术组(A组)、机械通气模型组(B组)、瘦素10μg/kg组(C组)和瘦素50μg/kg组(D组),每组12只。采用10%水合氯醛3.5 ml/kg麻醉大鼠,疼痛反射消失后C组腹腔注射瘦素10μg/kg,D组腹腔注射瘦素50μg/kg,A、B组腹腔注射等容量生理盐水,注射后即刻进行气管切开,插管机械通气。A组气管插管后保留自主呼吸,B、C、D组机械通气建立VILI模型,参数设置:V_T 20 ml/kg,RR 80次/分,I∶E 1∶1,FiO_2 21%,PEEP 0 mmHg,通气时间4 h。分别于基础状态、通气结束时抽取股动脉血进行血气分析。通气结束后放血处死大鼠,在4℃下取肺组织并收集支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF),光镜下进行中性粒细胞计数,采用ELISA法测定TNF-α、IL-6、IL-1β浓度;取肺组织称重,计算肺湿干重比(W/D);观察肺组织病理改变并进行病理评分;采用Western blot检测肺组织研磨液中NF-κB p65含量。结果与A组比较,B、C、D组W/D、肺损伤评分、BALF中性粒细胞计数、TNF-α、IL-6、IL-1β浓度及肺组织NF-κB p65含量明显升高(P0.01)。与B组比较,C、D组BALF中性粒细胞计数、TNF-α、IL-6、IL-1β浓度及肺组织肺损伤评分、NF-κB p65含量明显降低(P0.05)。与C组比较,D组BALF中性粒细胞计数、TNF-α、IL-6、IL-1β浓度及肺组织肺损伤评分、NF-κB p65含量明显降低(P0.05)。结论瘦素可降低大鼠机械通气肺损伤中炎性因子的表达水平,减轻肺损伤,50μg/kg较10μg/kg作用明显。     

鸢尾素对呼吸机相关性肺损伤大鼠细胞焦亡的影响

目的探讨鸢尾素对呼吸机相关性肺损伤大鼠细胞焦亡的影响。方法健康清洁级雄性SD大鼠36只, 体重200～250 g, 6～8周龄, 采用随机数字表法分为3组(n=12):对照组(C组)、呼吸机相关性肺损伤组(V组)和呼吸机相关性肺损伤+鸢尾素组(V+I组)。V+I组机械通气前尾静脉注射鸢尾素1 μg/kg。机械通气(潮气量40 ml/kg, 通气频率60次/min, 吸呼比设为1∶2, PEEP 0, FiO2 21%)4 h后采集股动脉血样, 进行动脉血气分析, 记录PaO2, 计算氧合指数(OI);收集支气管肺泡灌洗液(BALF), 测定总蛋白浓度, 采用ELISA法测定BALF和血清IL-1β、IL-18浓度。取肺组织, HE染色后行肺损伤评分, 测定肺组织湿重/干重(W/D)比值;分别采用Western blot法和RT-PCR法检测焦亡相关蛋白消皮素D-N端(GSDMD-N)、caspase-1及其mRNA的表达水平。结果与C组比较, V组肺损伤评分和W/D比值升高, PaO2和OI降低, BALF总蛋白浓度、BALF和血清IL-1β、IL-18浓度升高, 肺组织caspase...     

参附注射液对大鼠机械通气相关性肺损伤的保护作用及其机制

目的 探讨参附注射液(Shenfu injection,SF)对大鼠机械通气(mechanical ventilation,MV)相关性肺损伤的保护作用及其机制. 方法 40只健康成年雄性Wister大鼠采用随机数字表法分为4组,每组10只:对照组(C组)、正常潮气量MV组(N组)、大潮气量MV组(L组)、大潮气量MV+SF处理组(SF组).C组保留自主呼吸;N组、L组和SF组MV4h,潮气量分别设置为8～10 ml/kg、40 ml/kg、40 ml/kg,SF组于MV前15 min静脉注射SF 10 ml/kg.实验结束处死动物,收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF),测定BALF中总蛋白、IL-1β、IL-18和TNF-α的浓度;取肺组织,测量湿/干重比(wet/dry,W/D),采用免疫组化法检测肺组织NF-κB的表达,观察病理学改变并进行肺损伤评分. 结果 SF组BALF中TNF-α、IL-1β、IL-18浓度分别为(65±11)、(47±9)、(58±8) ng/L,较L组(99±7)、(69±7)、(86±7) ng/L明显降低(P＜0.05);SF组大鼠肺损伤评分、W/D、肺组织NF-κB光密度值分别为(8.5±1.8)分、(5.0±1.6)、(0.32±0.28),较L组(14.1±2.7)分、(5.5±1.8)、(0.54±0.33)均明显降低(P＜0.05). 结论 SF可减轻大鼠MV相关性肺损伤,其机制可能与SF抑制肺内NF-κB通路的活性且降低肺内炎性因子的释放有关.     

丙泊酚对大鼠机械通气相关肺损伤的保护作用及机制

目的 探讨丙泊酚对大鼠机械通气相关肺损伤影响的作用机制.方法 24只Wistar清洁级大鼠随机分为3组(n=8),采用压力控制机械通气模式通气4 h.A组为模型组,通气模式为吸气峰压(PIP)=25 cm H2O(1 cm H2O=0.098 kPa),呼气末正压(PEEP)=2 cm H2O;B、c组为同时输注丙泊酚组,通气模式同A组,B组输注模式为静注2mg/kg,继以4mg·kg-1·h-1速度持续输注;C组输注模式为5 mg/kg,继以10 mg·kg-1·h-1速度持续输注,记录基础时点、1、2、3、4 h的MAP、HR和动脉血气.4 h后处死全部大鼠,测量肺组织湿/干比(W/D),支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中总蛋白、肿瘤坏死因子α(tumor necrosis factora,TNF-α)、白介素1β(interleukin1β,IL-1β)、白介素6(interleukin6,IL-6)、白介素10(interleukin10,IL-10)和巨噬细胞炎性蛋白2(macrophage inflammatorv protein2,MIP-2)的含量,肺组织匀浆中丙二醛(malondialdehyde,MDA)和超氧化物歧化酶(superoxide dismutase,SOD)的含量,观察肺组织病理形态学变化.结果 A组MAP和PaO2在4 h时显著降低,由(116.0±7.4)mm Hg(1 mm Hg=0.133 kPa)和(379±65)mm Hg降低到(73±21)mm Hg和(103±48)mm Hg,与基础值相比差异有统计学意义(P<0.05),而B、C组与基础值相比差异无统计学意义.在4 h时A组的PaCO2显著升高(P<0.05),而B、C两组与基础值相比差异无统计学意义.肺组织湿/干比、BALF中总蛋白含量、TNF-α和MIP-2浓度A组明显高于B、C组(P<0.05),肺组织匀浆巾MDA浓度A组明显高于B、C组(P<0.05),A组SOD浓度也有所降低,但和B、C组差异无统计学意义.肺组织学病理评分B、C组也好于A组(P<0.05),B、C组间差异无统计学意义.结论 丙泊酚可减轻大鼠机械通气相关肺损伤,其机制可能与其减少炎症因子的释放,减少中性粒细胞在肺内的积聚,抑制过氧化损伤有关.     

黏着斑激酶在机械通气相关性肺损伤中的作用

背景 机械通气相关性肺损伤(ventilator-induced lung injury,VILI)是指应用呼吸机过程中由于机械通气的各种因素与肺部原发病共同作用导致的肺组织损伤.肺损伤过程中肺微血管的完整性破坏及通透性改变是引起VILI的根本原因.紧密连接(tight junction,TJ)及黏附连接(adherent junction,AJ)是细胞连接的主要方式,对维持肺的正常功能起着重要作用.黏着斑激酶(focal adhesion kinase,FAK)主要作用于细胞膜黏附连接的黏着斑部位,能维持黏着斑蛋白在细胞膜的表达,对AJ及血管通透性具有重要作用. 目的 通过对FAK在VILI中的作用的研究指导临床实践. 内容 探讨机械通气对FAK的影响及FAK对AJ、TJ的影响和作用. 趋向 进一步明确FAK在VILI发生过程中的作用,为临床预防及治疗VILI提供新思路及理论依据.     

Rho/Rock 信号通路在大鼠呼吸机相关性肺损伤中的作用

目的评价Rho/Rock信号通路在大鼠呼吸机相关性肺损伤(ventilator-induced lung injury,VILI)中的作用。方法选择健康雄性SD大鼠96只,12~15周龄,体重300~350g,采用随机数字表法将大鼠随机分为四组:空白对照组(C组)、Rho激酶抑制药法舒地尔组(F组)、高潮气量组(H组)和高潮气量+Rho激酶抑制药法舒地尔组(HF组),每组24只。C组和F组不行机械通气,H组和HF组行高潮气量40ml/kg机械通气4h。F组和HF组在机械通气前1h给予腹腔注射法舒地尔10mg/kg。分别于通气前(T0)、通气后4h(T1)、8h(T2)和24h(T3)每组随机取6只大鼠,采集血样,测定血清TNF-α、IL-6及IL-10浓度;采血结束后处死大鼠,收集支气管肺泡灌洗液(BALF),采用考马斯亮兰法检测BALF总蛋白;测定肺组织湿/干重比(W/D);光镜下行肺组织病理学损伤评分;采用分光光度法检测肺组织髓过氧化物酶(MPO)活性;采用Western blot和RT-PCR法分别检测肺组织RhoA、Rock2蛋白含量和mRNA表达水平。结果与C组比较,T1~T3时H组和HF组大鼠血清TNF-α、IL-6及IL-10浓度、BALF总蛋白含量、肺组织W/D、病理学损伤评分、MPO活性、RhoA、Rock2蛋白含量和mRNA表达水平明显升高(P0.05);与H组比较,T1~T3时HF组大鼠血清TNF-α、IL-6浓度、BALF总蛋白含量、肺组织W/D、病理学损伤评分、MPO活性、RhoA、Rock2蛋白含量和mRNA表达水平明显下降,血清IL-10浓度明显升高(P0.05)。结论Rho激酶抑制药法舒地尔可减轻大鼠呼吸机相关性肺损伤,其机制可能与其抑制Rho/Rock信号通路,降低肺组织内炎性反应有关。     

Dexmedetomidine regulates inflammatory molecules contributing to ventilator-induced lung injury in dogs

Background

Dexmedetomidine reduced mortality and inhibited the inflammatory response during endotoxemia in rats. The aim of this study was to clarify the effect of dexmedetomidine-regulating inflammation on a noninfectious, ventilator-induced lung injury (VILI) in dogs.

Methods

Thirty healthy Beagles weighing between 8 and 12 kg were randomly divided into five groups: control group (group C, n = 6), mechanical ventilation (group MV, n = 6), and three different doses of dexmedetomidine group (group DEX1–3, n = 6). VILI was induced by high-tidal volume ventilation (tidal volume 20 mL/kg; respiratory rate 15 breaths/min; FiO₂ 0.5). Group DEX received intravenous Dex 20 min before endotracheal intubation (0.5, 1.0, and 2.0 μg/kg Dex was infused within 20 min and then a maintenance dose of 0.5, 1.0, and 2.0 μg/kg/h Dex was infused intravenously). Arterial blood samples were obtained from femoral artery at base state, MV1h, MV2h, and MV4h for blood gas analysis. After being mechanically ventilated for 4 h, dogs were killed and the levels of pulmonary inflammatory response and polymorphonuclear neutrophils (PMNs) count in bronchoalveolar lavage fluid were evaluated.

Results

Histologic findings of the MV, DEX1, DEX2, and DEX3 groups revealed severe, moderate, mild, and normal to minimal inflammation, respectively. Myeloperoxidase level, PMNs/alveoli ratio, nuclear factor-κB messenger RNA (mRNA), tumor necrosis factor-alpha mRNA, and inducible nitric oxide synthase mRNA expression in lung tissues of the DEX2 and DEX3 were significantly lower than those of the MV group. Partial pressures of oxygen was decreased significantly at MV4h as compared with the baseline. There was no statistical significance in partial pressures of oxygen between MV and DEX2 group as well as between group MV and group DEX3.

Conclusions

Dexmedetomidine could mitigate pulmonary inflammatory response induced by VILI in dogs.     

亚甲蓝对大鼠机械通气相关肺损伤中核苷酸结合寡聚化结构域样受体蛋白3炎性小体的影响

目的评价亚甲蓝对大鼠机械通气相关损伤(VILI)中核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体的影响。方法清洁级成年雄性SD大鼠36只,8周龄,体重240～260 g,采用随机数字表法分为三组:自主呼吸对照组(C组)、大潮气量模型组(H组)和大潮气量+亚甲蓝组(MB组),每组12只。三组大鼠均行气管切开插管术,MB组经腹腔注射1%亚甲蓝50 mg/kg,10 min后以V_T 20 ml/kg行机械通气;C组经腹腔注射等容量生理盐水后保持自主呼吸;H组经腹腔注射等容量生理盐水,10 min后以V_T 20 ml/kg行机械通气。通气参数:FiO_2 21%,I∶E 1∶1,RR 80次/分,PEEP 0,通气时间4 h。于基础状态、通气结束时经颈总动脉取血行血气分析,通气结束后颈总动脉放血处死大鼠,收集肺组织标本、支气管肺泡灌洗液(BALF)。光镜下观察肺组织病理学改变,记录肺损伤评分,计算肺组织湿/干重比值(W/D)。采用ELISA法测定BALF中总蛋白含量以及血清、BALF中白细胞介素(IL)-1β、IL-18浓度;鲁米诺化学发光法检测肺组织中活性氧(ROS)含量;RT-PCR法及Western blot法分别检测肺组织NLRP3、凋亡相关斑点样蛋白(ASC)、天冬氨酸半胱氨酸蛋白酶-1(caspase-1)mRNA表达量及蛋白含量。结果与C组比较,H组肺损伤评分、W/D明显升高(P0.01),BALF中总蛋白以及血清、BALF中IL-1β和IL-18浓度明显升高(P0.01),肺组织中ROS含量、NLRP3、ASC、caspase-1 mRNA表达量及蛋白含量明显升高(P0.01)。与H组比较,MB组肺损伤评分、W/D明显降低(P0.05),BALF中总蛋白以及血清、BALF中IL-1β和IL-18浓度明显降低(P0.05),肺组织中ROS含量、NLRP3、ASC、caspase-1 mRNA表达量及蛋白含量明显降低(P0.05)。结论亚甲蓝通过抑制大鼠肺组织中NLRP3炎性小体的激活,阻碍促炎因子IL-1β及IL-18的形成,减轻大鼠VILI。     

七氟醚减轻大鼠呼吸机相关性肺损伤

目的 探讨七氟醚对大鼠呼吸机相关性肺损伤(VILI)的影响并探讨其可能机制。方法 健康SPF级雄性SD大鼠36只,6～8周龄,体重220～280 g。随机分为三组：对照组(C组)、VILI组(V组)和七氟醚组(S组),每组12只。大鼠给予1%戊巴比妥钠40 mg/kg麻醉后行气管切开插管术,C组自主呼吸4 h, V组和S组插管后机械通气4 h, S组机械通气期间吸入2%七氟醚4 h。通气参数：V_T 20 ml/kg, RR 80次/分,I∶E 1∶1,FiO₂ 21%,PEEP 0 cmH₂O。机械通气结束时采集股动脉血测定PaO₂。处死大鼠,取肺组织和支气管肺泡灌洗液(BALF),计算肺组织湿/干重比值(W/D),采用ELISA法检测BALF中白细胞介素(IL)-1β、IL-18浓度,二氯荧光黄双乙酸盐法检测BALF中肺泡巨噬细胞活性氧(ROS)水平,Western blot法及qRT-PCR法检测肺组织NF-E2相关因子2(Nrf2)、NLRP3、凋亡相关斑点样蛋白(ASC)、caspase-1...     

异丙酚减轻大鼠机械通气所致肺损伤

目的探讨异丙酚对大鼠高压力机械通气所致急性肺损伤的影响。方法24只Wistar大鼠随机分为3组（n=8）,采用压力控制机械通气模式通气。A组为对照组,通气模式为PIP=25 cmH2O,PEEP=2 cm H2O;B、C两组为异丙酚组,通气模式同A组,B组输注模式为静注2 mg／kg,继以4 mg·ks^-1·h^-1速度持续输注;C组输注模式为静注5 mg／kg,继以10 mg·kg^-1·h^-1速度持续输注,记录基础时点、1h、2 h、3 h、4 h的MAP、HR和动脉血气。4 h后处死全部大鼠。测量肺组织湿干比、BALF中蛋白含量,观察肺组织病理形态学变化。结果A组MAP、PaO2和pH在4 h时显著降低,与基础值相比有统计学差异（P〈 0．05）,而B、C两组与基础值相比无明显变化。在4h时A组的PaCO2显著升高（P〈0．05）,而B、C两组与基础值相比无明显变化。肺组织湿／干比和BALF中蛋白含量A组亦明显高于B、C两组（P〈0．05）。B、C组间无显著差别。肺组织形态学改变B、C组好于A组,肺组织中性粒细胞浸润程度也较轻。结论异丙酚对机械通气所致急性肺损伤具有保护作用,其机制可能与减少中性粒细胞在肺内浸润有关。     

丙泊酚对大鼠机械通气相关肺损伤的保护作用及机制

Objective To investigate the mechanisms of propofol on ventilator-induced lung injury in rats produced by high PIP ventilation. Methods Twenty-four anesthetized Wistar rats weighting 280 g-320 g were randomly divided into tlhree groups (n=8). Rats were ventilated with high PIP pattern (PIP=25 cm H2O,PEEP=2 cm H2O) for 4 h. Propofol was given in a bolus of 2 mg/kg (group B) or 5 mg/kg (group C), followed by continuous infusion with 4 mg·kg-1·h-1 (group B)or 10 mg·kg-1·h-1(group C). No Propofol was given for group A. MAP, HR were recorded and arterial blood gases were analyzed. Lung wet and dry weight ratio( W/D), tumor necrosis factora(TNF-α), interleukin1β(IL-1β), IL-6, IL-10, macrophage inflammatory protein2(MIP-2) and protein content in bronchoalveolar lavage fluid (BALF) , content of malondialdehyde (MDA) and superoxide dismutase (SOD) in lung homogenate were determined.Pathological change of lung was examined and lung injury was scored as well. Results MAP and PaO2 decreased from (116±7.4) mm Hg and (379±65) mm Hg to (73±21 )mm Hg and (103±48)mm Hg, and PaCO2 increased at fourth hour in group A(P<0.05). PaO2 in group B and C were higher than in group A after 3 h(P<0.05). Lung W/D weight ratio, TNF-α, MIP-2 and protein content in BALF were higher in group A (P<0.05), and MDA was higher in group A (P<0.05). No significant difference between group B and C. Pathological changes of lung in group B and C were all better than those in group A. Conclusion Propofol may attenuate VILI in rats partly by reducing the release of cytokine, decreasing the accumulation of neutrophil in the lung, and inhibiting peroxidized injury.     

丙泊酚对大鼠机械通气相关肺损伤的保护作用及机制

Objective To investigate the mechanisms of propofol on ventilator-induced lung injury in rats produced by high PIP ventilation. Methods Twenty-four anesthetized Wistar rats weighting 280 g-320 g were randomly divided into tlhree groups (n=8). Rats were ventilated with high PIP pattern (PIP=25 cm H2O,PEEP=2 cm H2O) for 4 h. Propofol was given in a bolus of 2 mg/kg (group B) or 5 mg/kg (group C), followed by continuous infusion with 4 mg·kg-1·h-1 (group B)or 10 mg·kg-1·h-1(group C). No Propofol was given for group A. MAP, HR were recorded and arterial blood gases were analyzed. Lung wet and dry weight ratio( W/D), tumor necrosis factora(TNF-α), interleukin1β(IL-1β), IL-6, IL-10, macrophage inflammatory protein2(MIP-2) and protein content in bronchoalveolar lavage fluid (BALF) , content of malondialdehyde (MDA) and superoxide dismutase (SOD) in lung homogenate were determined.Pathological change of lung was examined and lung injury was scored as well. Results MAP and PaO2 decreased from (116±7.4) mm Hg and (379±65) mm Hg to (73±21 )mm Hg and (103±48)mm Hg, and PaCO2 increased at fourth hour in group A(P<0.05). PaO2 in group B and C were higher than in group A after 3 h(P<0.05). Lung W/D weight ratio, TNF-α, MIP-2 and protein content in BALF were higher in group A (P<0.05), and MDA was higher in group A (P<0.05). No significant difference between group B and C. Pathological changes of lung in group B and C were all better than those in group A. Conclusion Propofol may attenuate VILI in rats partly by reducing the release of cytokine, decreasing the accumulation of neutrophil in the lung, and inhibiting peroxidized injury.