外源性肺表面活性物质对呼吸机相关性肺损伤大鼠炎性反应的影响

目的 探讨外源性肺表面活性物质(PS)对呼吸机相关性肺损伤(VILI)大鼠炎性反应的影响.方法 成年雄性Wistar大鼠28只,体重310-388 g,采用随机数宁表法,将大鼠随机分为4组(n=7),对照组(C组)、VILI组、PS组和空气对照组(A组).采用高气道压机械通气(气道峰压40cmH2O,通气频率20次/min,PEEP 0)20 rin制备VILI模型.C组麻醉后即经股动脉放血处死.VILI 组于模型制备成功后放血处死.PS组和A组造模后采用自制吸痰管吸除气道内水肿液后经气道分别注入PS 100 mg/kg(50 mg/ml)和等容量空气,行机械通气(VT10 ml/kg,通气频率45次/min,PEEP 7.5cm H2O)120 min后放血处死.采集股动脉血样及气道内水肿掖,采用ELISA法测定血浆IL-6、IL-10、巨噬细胞炎性蛋白-2(MIP-2)和TNF-α浓度,采用Bradford蛋白浓度测定法测定气道内水肿液蛋白浓度.光镜下观察肺组织病理学及中性粒细胞数目.结果 4组血浆TNF-α浓度比较差异无统计学意义(P ＞0.05).与C组比较,VILI组血浆MIP-2、IL-10和IL-6浓度及中性粒细胞计数升高(P＜0.05),气道水肿液量和水肿液蛋白浓度比较差异无统计学意义(P＞0.05).与A组比较,PS组中性粒细胞计数减少(P＜0.05),气道水肿液量和水肿液蛋白浓度比较差异无统计学意义(P＞0.05),血浆MIP-2、IL-10和IL-6浓度差异无统计学意义(P＞0.05).VILI组、A组和PS组肺组织炎性损伤明显.结论 外源性PS治疗VILI大鼠可减少肺组织中性粒细胞募集,但不能抑制炎性细胞因子的释放.     

COPD患者肺叶切除术时低潮气量通气的效果

目的 评价慢性阻塞性肺疾病(COPD)患者行肺叶切除术时低潮气量通气的效果.方法 择期行肺叶切除术的COPD患者28例,年龄65～84岁,ASA Ⅱ或Ⅲ级,随机分为常规潮气量组(TV组,n=14)和低潮气量组(LV组,n=14).均于气管插管后行机械通气,参数设置:TV组潮气量(VT)为10 ml/kg,呼气末正压(PEEP)为0;LV组Vr为5～6 ml/kg,PEEP为0～5 cm H2O.采用旁气流法监测气道峰压(Ppeak)、气道平台压(Pplat)、气道阻力(Raw)及动态肺顺应性(Cd).于平卧位双肺通气10 min(T1)、侧卧位单肺通气90 min(T2)、术毕平卧位双肺通气10 min(T3)及术后24 h(T4)时取桡动脉血样,行血气分析,计算氧合指数(OI)、肺泡.动脉血氧分压差[P(A-a)O2]及呼吸指数(RI);取颈内静脉血样,测定血清肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)的浓度.结果 与T1时比较,2组T2-4时血清TNF-α及IL-6浓度升高(P<0.05);与TV组比较,LV组T2-4时血清TNF-α及IL-6浓度降低(P<0.05),T1-3时Ppeak及Raw降低,T2.3时Cd升高(P<0.05).T1-4时2组OI、RI及P(A-a)O2差异无统计学意义(P0.05).结论 低VT,通气可通过降低炎性反应,减轻COPD患者肺叶切除术时机械通气诱发的肺损伤.     

不同程度呼吸机相关性肺损伤大鼠血清CC10蛋白水平的比较

目的 比较不同程度呼吸机相关性肺损伤(VILI)大鼠血清CCIO蛋白的水平.方法 清洁级Wistar大鼠40只,雌雄不拘,体重200～250 g,随机分为5组(n=8),对照组(Ⅰ组)仅切开气管,不行机械通气;轻度肺损伤组(Ⅱ组)潮气量(VT)7 ml/kg,机械通气2 h;中度肺损伤组(Ⅲ组)VT 7 ml/kg,机械通气4 h;重度肺损伤组(Ⅳ组)VT 40 ml/kg,机械通气2 h;极重度肺损伤组(Ⅴ组)VT 40 ml/kg,机械通气4 h.Ⅰ组在气管切开后即刻,其余各组在机械通气结束时采集腹主动脉血3 ml,并收集支气管肺泡灌洗液(BALF),测定血清和BALF中CC10蛋白水平;观察肺Clara细胞;计算肺湿/干重比(W/D).结果 Ⅳ组和Ⅴ组终末细支气管、呼吸细支气管管腔有大量脱落Clara细胞,血管壁有大量漏出的CC10蛋白,其余组上述表现不明显;Ⅱ组～Ⅴ组血清CC10蛋白水平逐渐升高,肺组织损伤程度逐渐加重(P＜0.05);与Ⅰ组、Ⅱ组和Ⅲ组比较,Ⅳ组和Ⅴ组BALF中CC10蛋白水平降低(P＜0.05);血清CC10蛋白水平与肺组织损伤程度和肺W/D呈正相关,相关系数分别为0.915和0.846(P＜0.01);BALF中CC10蛋白水平与肺组织损伤程度和肺W/D呈负相关,相关系数分别为-0.799和-0.816(P＜0.01).结论 血清CC10蛋白水平与大鼠呼吸机相关性肺损伤程度有关.     

桑菊清解汤对大鼠呼吸机相关性肺损伤的影响

目的 评价桑菊清解汤对大鼠呼吸机相关性肺损伤的影响.方法 健康成年SD大鼠36只,雌雄不拘,体重300～ 350 g,采用随机数字表法,将其随机分为3组(n=12):对照组(C组)、机械通气组(V组)和桑菊清解汤组(SJ组).采用大潮气量(VT=40 ml/kg)机械通气2.5h制备大鼠呼吸机相关性肺损伤模型.SJ组于术前10 d采用桑菊清解汤300 g灌胃,1次/d,于第10次灌胃后2h时开始制备模型,V组和C组给予等容量生理盐水.于机械通气前(T0)、机械通气结束(T1)、机械通气后30 min(T2)时采集股动脉血样测定动脉血气,计算呼吸指数(RI)和氧合指数(OI),然后处死大鼠,取肺组织,采用双抗体夹心ELISA法测定肺组织TNF-α、IL-6和IL-10的含量,测定肺组织湿/干重(W/D)比,光镜下观察肺组织病理学结果.结果 与C组比较,V组和SJ组T1.2时RI升高,OI降低,肺组织TNF-α、IL-6、IL-10含量和W/D比升高(P＜0.05);与V组比较,SJ组RI降低,OI升高(P＜0.05),SJ组肺组织TNF-α、IL-6含量和W/D比降低,IL-10含量升高(P＜0.05).SJ组肺组织病理学损伤较V组减轻.结论 桑菊清解汤可减轻呼吸机相关性肺损伤,其机制与抑制炎性反应有关.     

小潮气量联合PEEP对单肺通气时胸外科手术患者血管外肺水的影响

目的 探讨小潮气量联合呼气末正压(PEEP)对单肺通气时胸外科手术患者血管外肺水的影响.方法 食道癌手术患者40例,年龄45～80岁,体重48～83kg,性别不限,ASA分级Ⅰ或Ⅱ级,随机分为2组(n=20):传统模式单肺通气组(Ⅰ组)机械通气模式为间歇正压通气(IPPV),VT9 ml/kg,通气频率12次/min;小潮气量联合PEEP单肺通气组(Ⅱ组)机械通气模式为IPPV联合PEEP5 cm H2O,VT6 ml/kg,通气频率15次/min.于麻醉诱导前(T0)、双肺通气30 min(T1)、单肺通气30 min(T2)、单肺通气1 h(T3)、恢复双肺通气拔管前(T4)和术后18 h(T5)时,记录血管外肺水(EVLW)、血管外肺水指数(EVLWI)、肺血管通透性指数(PVPI)和心输出量(CO),于T1～4时记录气道峰压(Ppeak);取股动脉血样,进行血气分析,并计算氧合指数(OI).结果 与Ⅰ组比较,Ⅱ组单肺通气期间EVLWI和.PVPI升高(P＜0.05),其余指标比较差异无统计学意义(P＞0.05);两组各时点OI、CO和Poeak比较差异无统计学意义(P＞0.05);与T0时比较,Ⅰ组T1时PVPI升高(P＜0.05),其余时点PVPI、EVLW和EVLWI差异无统计学意义(P＞0.05),Ⅱ组T2时EVLW、T1～4时EVLWI和T1.2时PVPI升高(P＜0.05);与T1时比较,Ⅰ组T2～5时EVLW、EVLWI和PVPI差异无统计学意义,Ⅱ组T5时PVPI降低(P＜0.05).结论 采用VT6 ml/kg、PEEP 5 cm H2O的单肺通气可增加患者血管外肺水,未对肺功能产生有利作用.     

外源性肺泡表面活性物质对大鼠呼吸机相关性肺损伤的保护作用

目的探讨气管注入肺泡表面活性物质(PS)对大鼠呼吸机相关性肺损伤(VILI)的保护作用及机制。方法将40只Wistar大鼠采用区组法随机分为对照组、高潮气量组(HV组)、VILI组和PS组4组,每组各10只。对照组未行机械通气,其余3组容量控制通气,PS组同时经气管内插管注入猪PS100mg/kg。监测心率、平均动脉压(MAP)、血气分析、肺湿/干重比(W/D)和支气管肺泡灌洗液(BALF)中白细胞计数,测定肺组织核因子-κB(NF-κB)活性和BALF中及血清白细胞介素-8(IL-8)浓度,并观察大体及光学显微镜下肺组织损伤的改变。结果损伤性机械通气后大鼠MAP及氧合指数(PaO2/FiO2)显著降低,而肺组织NF-κB活性和W/D显著增高。PS组与VILI组相比,MAP、PaO2/FiO2、肺组织NF-κB活性、BALF中白细胞计数、BALF及血清中IL-8浓度均有统计学意义(P<0.05)。组织学检查显示PS组较VILI组病变明显减轻。结论经气管注入PS可抑制VILI大鼠NF-κB基因表达,对VILI有保护作用。     

HSF1在小鼠呼吸机相关性肺损伤内源性保护机制中的作用：与HMGB1的关系

目的评价热休克转录因子1(HSF1)在小鼠呼吸机相关性肺损伤(VILI)内源性保护机制中的作用及其与高迁移率族蛋白B1(HMGB1)的关系。方法 SPF级健康C57BL/6雄性小鼠40只, 6～8周龄, 体质量20～25 g, 采用随机数字表法分为4组(n=10):对照组(C组)、VILI组、阴性对照siRNA+VILI组(NV组)和HSF1 siRNA+VILI组(siRNA组)。机械通气前48 h时, NV组气道内注射阴性对照siRNA 5 nmol, siRNA组气道内注射HSF1 siRNA 5 nmol, 均用无菌磷酸盐缓冲液稀释至50 μl。VILI组、NV组和siRNA组机械通气(VT 35 ml/kg, RR 75次/min, I∶E 1∶2, FiO2 21%)4 h构建小鼠VILI模型, C组仅行气管切开, 保留自主呼吸。分别于气管插管后即刻和机械通气4 h时, 行动脉血气分析, 记录PaO2;然后深麻醉下处死小鼠, 收集支气管肺泡灌洗液(BALF)和肺组织, 采用ELISA法测定BALF中TNF-α、IL-1β、HMGB1浓度, 测定肺组织湿重/干重(W/D)比值...     

组织蛋白酶B在大鼠呼吸机相关性肺损伤中的作用：与NLRP3炎症小体的关系

目的评价组织蛋白酶B(CTSB)在大鼠呼吸机相关性肺损伤(VILI)中的作用及其与NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎症小体的关系。方法 SPF级健康雄性SD大鼠36只, 6～8周龄, 体重220～300 g, 采用随机数字表法分为3组(n=12):对照组(C组)、VILI组(V组)和VILI+CA074-me组(Me组)。C组和V组大鼠气管插管前1 h腹腔注射等量生理盐水, Me组腹腔注射CA074-me 5 mg/kg。C组自主呼吸4 h, V组和Me组行机械通气4 h, 通气参数:VT 20 ml/kg, 通气频率80次/min, FiO2 21%, PEEP 0 cmH2O。气管插管前和自主呼吸或通气结束后采集股动脉血行动脉血气分析, 记录PaO2, 随后处死大鼠, 收集支气管肺泡灌洗液(BALF)和取肺组织, 确定肺组织湿重/干重(W/D)比值, HE染色法观察病理学结果并进行肺损伤评分, 采用ELISA法检测BALF及血清IL-1β和IL-18浓度。采用qRT-PCR法检测肺组织CTSB、NLRP3、凋亡相关斑点样蛋白(ASC)和caspase-1的mRNA表...     

丝裂原活化蛋白激酶在机械通气过程中对肺表面活性物质及特异蛋白基因表达的影响

目的 丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)在机械通气过程中对肺表面活性物质及特异蛋白基因表达的影响和可能机制. 方法 采用健康成年雄性Sprague-Dawley大鼠48只,体重250 g～320 g.采用3％戊巴比妥35 mg/kg～40 mg/kg腹腔注射麻醉后行气管切开置管术,完全随机分组方法分为6组(每组8只):①C组(对照组,麻醉后仅做气管切开不做机械通气)；②LV组[正常通气组,潮气量(Vt):6ml/kg,余同过度通气组]；③HV组[过度通气组,Vt:40 ml/kg,呼吸频率(RR)40次/min,吸呼比(I∶E)1∶2～1∶3,呼气末正压通气(PEEP) =0,吸入氧浓度(FiO2)21％,通气4 h]；④SP600125组(SP600125+ HV组,高潮气量通气前30 min给予MAPK拮抗剂SP600125)；⑤PD98059组(PD98059+ HV组,高潮气量通气前30 min给予MAPK拮抗剂PD98059)；⑥SB203580组(SB203580+ HV组,高潮气量通气前30 min给予MAPK拮抗剂SB203580).机械通气4h后(对照组气管切开后4h),采用RT-PCR方法测定肺表面活性蛋白(SP)-A、B、C和RTI40 mRNA表达量. 结果 ①与C组比较,LV组、HV组大鼠肺组织中RTI40表达均增加(P＜0.05),而HV组、SP600125 +HV组及SB203580+HV组肺组织中SP-A、SP-C表达均减少(P＜0.05),LV组中和PD98059+HV组中的SP-A、C变化均无统计学意义(P＞0.05)；②与HV组比较,SP600125+HV组、PD98059+HV组、SB203580+HV组肺组织中SP-A、C基因表达增加(P＜0.05),RTI40基因表达降低(P＜0.05)；③SP-A、C基因表达量在PD98059+HV组较SP600125+HV组、SB203580+HV组升高(P＜0.05)；④SP-B在各组中变化无统计学意义(P＞0.05). 结论 高潮气量机械通气致肺上皮细胞特异蛋白SP-A、C基因表达下降和RTI40基因表达上调,而MAPK拮抗剂可以防止该现象发生,提示MAPK影响呼吸机相关性肺损伤(ventilator-induced lung injury,VILI)过程中对肺上皮细胞的分泌功能.     

肺泡表面活性物质辅助治疗新生儿持续肺动脉高压的疗效观察

目的观察肺表面活性物质（PS）联合呼吸机机械通气治疗新生儿持续肺动脉高压（PPHN）的疗效。方法将40例达到机械通气标准的PPHN患儿分成2组。治疗组18例在常规机械通气基础上、采用从气管插管内滴入PS治疗,对照组22例给予常规机械通气治疗,其余治疗相同。比较分析两组肺动脉压、平均气道压、吸入氧浓度、血气分析、机械通气时间、氧疗时间、住院时间。结果治疗组与对照组在肺动脉压、平均气道压、吸入氧浓度、血气分析、机械通气时间、氧疗时间、住院时间方面均有显著性差异（P均〈0.05）。结论 PS联合呼吸机机械通气治疗PPHN能迅速缓解临床症状,缩短氧疗时间及住院时间。     

机械通气相关性肺损伤大鼠肺组织水通道蛋白5表达的变化

目的 评价机械通气相关性肺损伤大鼠肺组织水通道蛋白5(AQP5)表达的变化.方法 健康雄性SPF级SD大鼠70只,周龄7周,体重200～250 g,随机分为7组(n=10),对照组(A组)仅切开气管保留自主呼吸;不同通气时间小潮气量组(B_1组和B_2组)V_T 7 ml/kg,分别通气2 h或4 h;不同通气时间中潮气量组(C_1组和C_2组)V_T20 ml/kg,分别通气2 h或4 h;不同通气时间大潮气量组(D_1组和D_2组)V_T 40 ml/kg,分别通气2 h或4 h.A组在气管切开即刻,其余各组在机械通气结束时处死大鼠,开胸取肺组织行病理损伤评分,测定AQP5蛋白及其mRNA表达,计算肺组织湿/干重比值(W/D比值),收集肺泡灌洗液,计数中性粒细胞(PMN).结果 与A组比较,C_1组、C_2组、D_1组、D_2组AQP5蛋白及其mRNA表达下调,W/D比值、PMN计数和病理损伤评分升高(P＜0.05).与B_1组比较,C_1组和D_1组AQP5蛋白及其mRNA表达下调,W/D比值、PMN计数和病理损伤评分升高(P＜0.05).与B_2组比较,C_2组和D_2组AQP5蛋白及其mRNA表达下调,W/D比值、PMN计数和病理损伤评分升高(P＜0.05).与C_1组比较,D_1组AQP5蛋白及其mRNA表达下调,W/D比值、PMN计数和病理损伤评分升高(P＜0.05).与C_2组比较,D_2组AQP5蛋白及其mRNA表达下调,W/D比值、PMN计数和病理损伤评分升高(P＜0.05).结论 AQP5表达下调参与了机械通气诱发大鼠肺水肿的发生.     

反复肺复张联合肺保护性通气对急性呼吸窘迫综合征家兔肺损伤的影响

目的 评价反复肺复张联合肺保护性通气对急性呼吸窘迫综合征(ARDS)家兔肺损伤的影响.方法 家兔24只,雌雄各半,体重2.5～3.5 kg,采用随机数字表法,将兔随机分为4组(n=6):正常对照组(Ⅰ组)、ARDS模型组(Ⅱ组)、肺保护性通气组(Ⅲ组)和反复肺复张联合肺保护性通气组(Ⅳ组).麻醉下进行机械通气,Ⅱ组、Ⅲ组和Ⅳ组采用静脉输注油酸0.1 ml/kg(经15 min输注)的方法 制备ARDS模型,模型制备成功后经3 min确定静态压力.容积曲线低位转折点.Ⅰ组和Ⅱ组的通气参数为:VT12 ml/kg,通气频率30次/min,呼气末正压(PEEP)0,FiO2 1.0,氧流量1 L/min,吸气时间0.6 s,吸呼比1.0∶2.3;Ⅲ和Ⅳ组通气参数为:VT6 ml/kg,PEEP为静态压力-容积曲线低位转折点对应气道力+2 cm H2O,其他通气参数同Ⅰ组和Ⅱ组,Ⅳ组分别在确定静态压力-容积曲线低位转折点后即刻、1、2和3 h时实施肺复张.肺复张的方法:吸气压力为30 cm H2O,吸气时间为30 s.分别于每次肺复张后采集动脉血样,测定PaO2,计算氧合指数.最后一次肺复张后1 h处死动物,取肺组织,测定TNF-α和IL-10的含量、髓过氧化物酶(MPO)活性、丙二醛(MDA)含量和湿/干重比(W/D比),计算TNF-α与IL-10的比值(TNF-α/IL-10),光镜下观察肺组织病理学结果.结果 与Ⅰ组比较,Ⅱ组氧合指数降低,肺组织TNF-α/IL-10、MPO、MDA和W/D比升高(P＜0.05);与Ⅱ组比较,Ⅲ组氧合指数升高,肺组织TNF-α/IL-10、MPO、MDA和W/D比降低(P＜0.05);与Ⅲ组比较,Ⅳ组氧合指数升高,肺组织TNF-α/IL-10、MPO、MDA和W/D比降低(P＜0.05).Ⅳ组肺组织损伤程度轻于Ⅲ组.结论 与肺保护性通气比较,肺保护性通气期间反复肺复张可进一步减轻ARDS家兔肺损伤,其机制与抑制肺组织炎性反应有关.

Abstract：

Objective To evaluate the effect of alveolar recruitment maneuvers (ARM) combined with lung protection mechanical ventilation on lung injury in a rabbit model of acute respiratory distress syndrome (ARDS) .Methods Twenty-four rabbits of both sexes weighing 2.5-3.5 kg were randomly divided into 4 groups (n=6 each):normal control group(group Ⅰ);ARDS group(group Ⅱ);ARDS+lung protection mechanical ventilation group (group Ⅲ) and ARDS + lung protection mechanical ventilation + ARM group (group Ⅳ). The animals were anesthetized with iv pentobarbital 20 mg/kg, tracheostomized and mechanically ventilated. Anesthesia was maintained with iv gammahydroxybutyrate infusion 100 mg·kg-1·h-1 and intermittent iv boluses of vecuronium. ARDS was induced with oleic acid 0.1 ml/kg injected iv over 15 min in Ⅱ ,Ⅲ and Ⅳ groups. In Ⅰand Ⅱ groups VT = 12 ml/kg, RR=30 bpm, I∶E=1.0=2.3, PEEP=0, FiO2=1, while in Ⅲ and Ⅳ groups VT=6 ml/kg, RR=30 bpm, I∶E=1.0=2.3, PEEP=airway pressure at lower inflection point+2 cm H2O, FiO2=1.ARM was performed by increasing the airway pressure to 30 cm H2O for 30 s once an hour in group Ⅳ. Arterial blood gas analysis was performed after each ARM. The animals were sacrificed at 1 h after the 3rd ARM. The lungs were removed for microscopic examination and determination of W/D lung weight ratio, TNF-α, IL-10 and MDA contents and MPO activity. TNF-α/IL-10 ratio was calculated. Results ARDS significantly decreased PaO2/FiO2 and increased TNF-α/IL-10 and W/D lung weight ratio, MPO activity and MDA content in the lung tissue. Lung protection mechanical ventilation significantly increased PaO2/FiO2 and decreased TNF-α/IL-10 and W/ D lung weight ratio, MPO activity and MDA content in the lung tissue. Lung protection mechanical ventilation + ARM significantly increased PaO2/FiO2 and decreased TNF-α/IL-10, W/D lung weight ratio, MDA content and MPO activity in group Ⅳ. Conclusion ARM combined with lung protection mechanical ventilation can further attenuate ARDS-induced lung injury by inhibiting inflammatory response.     

Effects of surfactant replacement on alveolar overdistension and plasma cytokines in ventilator‐induced lung injury

Background: Overdistension of the lung causes ventilator‐induced lung injury (VILI) accompanied by surfactant abnormalities and inflammatory changes. We investigated the effects of surfactant replacement on overdistension of the terminal airspaces and plasma cytokine levels in VILI. Methods: VILI was induced by high‐pressure ventilation (HPV) in rats anesthetized with pentobarbital, followed by ventilation for 2 h in the maintenance mode (tidal volume=10 ml/kg, positive end‐expiratory pressure=7.5 cmH₂O) with or without surfactant replacement. The sizes of the terminal airspaces were determined after fixing the lungs at an airway pressure of 10 cmH₂O on deflation. Cytokine levels were assessed by enzyme‐linked immunosorbent assay. Results: The mean ratio of the largest terminal airspace size class (≥64,000 μm²) was increased from 13.4% to 32.0% by HPV (P<0.05). After maintenance‐mode ventilation, the ratio decreased to 16.1% with surfactant replacement (P<0.05), but increased to 44.6% without surfactant replacement (P<0.05). Mean macrophage inflammatory protein‐2 (MIP‐2) levels in the plasma increased from <0.02 to 6.9 ng/ml with HPV (P<0.05), and further increased to ≥11.8 ng/ml, regardless of surfactant replacement after maintenance‐mode ventilation. Similar tendencies were observed in the interleukin (IL)‐6 and IL‐10 levels. Tumor necrosis factor‐α levels were almost negligible during the experiment. Conclusion: In rats with VILI, surfactant replacement reversed overdistension of the terminal airspaces that may induce barotrauma, but not upregulation of MIP‐2, IL‐6, and IL‐10 within 2 h.     

麻醉诱导期开始采用肺保护性通气策略对妇科腔镜手术患者氧合及预后的影响

目的探讨从麻醉诱导期开始采用肺保护性通气策略对妇科腔镜手术患者氧合及预后的影响。方法选择在本院接受妇科腹腔镜手术的患者60例,随机分为三组,每组20例。采用间歇正压通气(IPPV)模式,氧浓度为100%,氧气流量2 L/min,吸呼比为1∶2。A组:从诱导期(即自主呼吸消失后,予面罩机械通气5 min)开始全程通气模式:VT6 ml/kg,RR 16次/分,PEEP为5cm H2O,每30分钟给予一次手法肺复张(手控通气,气道压力维持40 cm H2O,持续30 s);B组:诱导期通气模式:VT10 ml/kg,RR 10次/分,插管后通气模式:VT6 ml/kg,RR 16次/分,PEEP 5cm H2O,每30分钟给予一次手法肺复张;C组:全程通气模式均为VT10 ml/kg,RR 10次/分。记录插管前(T0)、气腹后(T1)、手术开始30 min(T2)、60 min(T3)、放气腹(T4)时的气道峰压(Ppeak)、平均气道压(Pmean)、计算肺顺应性(CL),并在T0、T1、T3、清醒拔管后吸空气5 min(T5)时抽取动脉血进行血气分析,计算氧合指数(OI)及肺内分流率(Qs/Qt)。记录患者术后并发症发生情况与住院天数。结果与T0时比较,T1~T4时三组Ppeak和Pmean均明显升高,C组Ppeak明显高于A组和B组(P0.05),T2时C组Pmean明显高于A组和B组(P0.05);三组CL在气腹后明显降低(P0.05),T3和T4时C组明显低于A组和B组(P0.05);三组PETCO2在气腹后明显升高,T2~T4时C组明显低于A组与B组(P0.05),A组与B组差异无统计学意义;三组OI随着时间延长变化差异无统计学意义,拔管后三组均明显降低(P0.05);三组Qs/Qt随着手术进行呈上升趋势,与T0时比较,三组在T3时明显上升(P0.05),C组明显大于A组和B组(P0.05);T5时均明显下降(P0.05)。术后仅C组有1例发生肺部感染。结论与常规通气相比,对接受妇科腔镜手术患者采用保护性肺通气策略能够明显改善患者的肺顺应性和氧合功能,有利于肺保护。     

大鼠呼吸机相关肺损伤热休克蛋白70和核因子-κB的表达及其意义

目的 探讨呼吸机所致肺损伤(VILI)炎症反应中热休克蛋白70(HSP70)和核因子-κB(NF-κB)表达的意义.方法 健康SD大鼠30只,实施麻醉和气管切开术后分别接受不同潮气量(VT)的通气(通气时间均为4 h).随机分为以下3组:对照组(A组);常规通气组(B组,VT=10ml/kg);损伤通气组(C组,VT=40ml/kg).4 h后放血处死动物,测定肺湿/干比重、髓过氧化物酶(MPO)活性及肺泡灌洗液(BALF)中总蛋白含量,光镜下行白细胞(WBC)计数;Western blot检测肺组织HSP70及NF-κB的表达.结果 在大潮气量机械通气4 h后,BALF中总蛋白含量、肺湿干比、WBC计数和MPO水平(3.89±0.31、5.83±0.42、6.10±0.80、7.31±1.21)均明显更高(P＜0.05);肺组织中HSP70、NF-κB表达水平(1.36±0.13、0.41±0.07)均显著增加,且两者呈负相关.结论 HSP70可通过抑制NF-κB的活性,保护肺组织避免VILI.     

Role of the renin-angiotensin system in ventilator-induced lung injury: an in vivo study in a rat model

BACKGROUND: Injurious mechanical ventilation can cause a pro-inflammatory reaction in the lungs. Recent evidence suggests an association of the renin-angiotensin system (RAS) with lung inflammation. A study was undertaken to investigate the pathogenic role of the RAS in ventilator-induced lung injury (VILI) and to determine whether VILI can be attenuated by angiotensin converting enzyme (ACE) inhibition. METHODS: Male Sprague-Dawley rats were mechanically ventilated for 4 h with low (7 ml/kg) or high (40 ml/kg) tidal volumes; non-ventilated rats were used as controls. Lung injury and inflammation were measured by the lung injury score, protein leakage, myeloperoxidase activity, pro-inflammatory cytokine levels and nuclear factor (NF)-kappaB activity. Expression of the RAS components was also assessed. Some rats were pretreated with the ACE inhibitor captopril (10 mg/kg) for 3 days or received a concomitant infusion with losartan or PD123319 (type 1 or type 2 angiotensin II receptor antagonist) during mechanical ventilation to assess possible protective effects on VILI. RESULTS: In the high-volume group (n=6) the lung injury score, bronchoalveolar lavage fluid protein concentration, pro-inflammatory cytokines and NF-kappaB activities were significantly increased compared with controls (n=6). Lung tissue angiotensin II levels and mRNA levels of angiotensinogen and type 1 and type 2 angiotensin II receptors were also significantly increased in the high-volume group. Pretreatment with captopril or concomitant infusion with losartan or PD123319 in the high-volume group attenuated the lung injury and inflammation (n=6 for each group). CONCLUSIONS: The RAS is involved in the pathogenesis of ventilator-induced lung injury. ACE inhibitor or angiotensin receptor antagonists can attenuate VILI in this rat model.     

Effect of ventilatory rate on airway cytokine levels and lung injury

BACKGROUND: Controversy exists regarding the effect of large-volume mechanical ventilation (MV), as a sole stimulus, on the pulmonary cytokine milieu. We used a well described experimental model of ventilator-induced lung injury (VILI) to examine the impact of large volume ventilation on pulmonary cytokines in vivo and to study the effect of respiratory rate (RR) variation on these levels. MATERIALS AND METHODS: Sixty rats (410 +/- 47 g) were randomized to: 1) non ventilated control; 2) V(t) = 40 ml/kg, RR = 40 bpm; 3) V(t) = 40 ml/kg, RR = 20 bpm; 4) V(t) = 7 ml/kg, RR = 40 bpm; or 5) V(t) = 7 ml/kg, RR = 20 bpm. After 1 h of MV, bronchoalveolar lavage (BAL) and serum were collected. BAL was analyzed for urea, protein, lactate dehydrogenase (LDH), tumor necrosis factor (TNF)alpha and interleukin (IL)-6. Epithelial lining fluid volume (ELF) was calculated. RESULTS: Regardless of RR, animals ventilated at 7 ml/kg did not differ from control in any outcome. In contrast, MV at 40 ml/kg V(t) with 40 bpm produced lung injury characterized by significant elevations of BAL TNFalpha, IL-6, protein, ELF, and LDH. At 40 ml/kg V(t), RR reduction (20 bpm) significantly reduced all injury measures. CONCLUSION: This study confirms that large-volume MV, as a sole stimulus, produces lung injury and cytokine release. Whereas increasing RR at low V(t) has little impact on injury parameters, RR reduction under VILI-promoting conditions significantly limits lung injury.     

不同潮气量机械通气对创伤后急性呼吸窘迫综合征疗效的影响

目的探讨小潮气量(LTV)加呼气末正压(PEEP)机械通气(MV)治疗创伤后急性呼吸窘迫综合征(ARDS)的疗效。方法以18例常规潮气量(8～12ml/kg)MV为对照组,20例小潮气量(5～7ml/kg)加用PEEP的MV模式为观察组,比较两组间血气,RR、HR、MAP、CVP、呼吸机所致肺损伤(VILI)、多脏器功能不全(MODS)发生率及ARDS病死率。结果两组PaO2差异无显著性意义(P>0.05);观察组PaCO2高于对照组(P<0.05);观察组无VILI、MODS及死亡病例发生,对照组2例VILI、2例ARDS并发MODS死亡。结论在ARDS治疗中采用小潮气量加PEEP及允许范围内高碳酸血症(PHC)的保护性通气策略,可明显改善缺氧,减少VILI发生,从而降低其病死率。