机械通气对糖尿病小鼠肺微血管通透性的影响

目的 观察机械通气对糖尿病小鼠肺微血管通透性的影响.方法 雄性SPF级C57/BL6小鼠64只,10～ 12周龄,体重20～25 g,采用随机数字表法,将其随机分为4组(n=16):对照组(C组)、机械通气组(M组)、糖尿病组(D组)和糖尿病机械通气组(DM组).D组和DM组腹腔注射链脲佐菌素150 mg/kg,以0.1 mol/L枸橼酸盐缓冲液溶解制备小鼠糖尿病模型,气管切开后自主呼吸通气4h.C组和M组腹腔注射等容量枸橼酸缓冲液,气管切开后接呼吸机行机械通气4h.每组随机取8只小鼠,采集动脉血样,测定PaO2;然后处死小鼠,取肺组织,电镜下观察超微结构,测定湿/干比(W/D比)和髓过氧化物酶(MPO)活性.每组随机处死4只小鼠,测定肺微血管通透性.每组随机取4只小鼠,体外原代细胞培养肺微血管内皮细胞并鉴定,采用跨内皮细胞的[14C]BSA检测肺微血管内皮细胞通透系数.结果 与C组比较,M组、D组和DM组PaO2降低,肺组织MPO活性、肺微血管通透性和内皮细胞通透系数升高,M组和DM组肺组织W/D比升高(P＜0.05);与D组比较,DM组PaO2降低,肺组织W/D比、MPO活性、肺微血管通透性和内皮细胞通透系数升高(P＜0.05).结论 机械通气导致糖尿病小鼠肺损伤可能与肺微血管通透性增加有关.     

p38MAPK信号通路在盐酸戊乙奎醚减轻内毒素诱导人脐静脉内皮细胞损伤中的作用

目的 探讨p38丝裂原活化蛋白激酶(p38 MAPK)信号通路在盐酸戊乙奎醚减轻内毒素诱导人脐静脉内皮细胞损伤中的作用.方法 培养人脐静脉内皮细胞,以1×104/ml密度接种于96孔培养板(100μl/孔)或24孔培养板(3 ml/孔),以1×106/ml密度接种于培养瓶(5 ml/瓶),采用随机数字表法,将其随机分为4组(n=23):正常对照组(C组)、脂多糖(LPS)组(L组)、盐酸戊乙奎醚组(P组)和盐酸戊乙奎醚+LPS组(PL组),P组和PL组加入终浓度为2μg/ml的盐酸戊乙奎醚,L组和PL组加入终浓度为1 μg∥ml的LPS,PL组于加入盐酸戊乙奎醚后1h加入LPS.加入LPS后24h时,收集细胞,测定磷酸化p38 MAPK(p-p38 MAPK)和p38 MAPK的表达水平,以二者比值反映p38 MAPK激活程度,并测定细胞活力、NO含量和诱导型一氧化氮合酶(iNOS)表达.结果 与C组比较,L组细胞活力降低,NO、p-p38 MAPK和p38 MAPK激活程度升高,iNOS表达上调(P＜0.01),P组上述指标差异无统计学意义(P＞0.05);与L组比较,PL组细胞活力升高,NO、p-p38 MAPK和p38 MAPK激活程度降低,iNOS表达下调(P＜0.05或0.01).结论 p38 MAPK信号通路参与了盐酸戊乙奎醚减轻内毒素诱导人脐静脉内皮细胞损伤的作用.     

右美托咪定、地佐辛单独或复合用药对开胸术患者苏醒期躁动的影响

目的 评价右美托咪定、地佐辛单独或复合用药对开胸术患者苏醒期躁动的影响.方法 择期拟行开胸术患者80例,ASA分级Ⅰ或Ⅱ级,年龄18～64岁,体重48～75 kg,采用随机数字表法,将其分为4组(n=20):对照组(C组)、右美托咪定组(DEX组)、地佐辛组(DEZ组)和右美托咪定+地佐辛组(DEX+ DEZ组).DEX组于麻醉诱导前15 min时静脉注射右美托咪定0.5 μg/kg,继静脉输注0.4 μg·kg-1·h-1至关胸开始,DEZ组于关胸开始静脉注射地佐辛0.1 mg/kg,DEX+ DEZ组于麻醉诱导前15 min时静脉注射右美托咪定0.5 μg/kg,继静脉输注0.4 μg· kg-1 ·h-1至关胸开始,静脉注射地佐辛0ˉ1 mg/kg,C组麻醉诱导前15 min开始至关胸开始时给予等容量生理盐水.每组缝皮开始时静脉注射氟比洛芬酯50 mg.分别于麻醉诱导前10 min (T1)、关胸完毕缝皮前(T2)、拔除气管导管即刻(T3)、拔除气管导管后15 min(T4)时抽取肘静脉血样,采用ELISA法测定血浆C-反应蛋白(CRP)、TNF-α和IL-10的浓度,记录患者苏醒期躁动等不良反应的发生情况,采用Ramsay评分评价镇静程度.结果 与C组比较,DEX组、DEZ组和DEX+ DEZ组T2-4时血浆CRP、TNF-α浓度降低,IL-10浓度升高,TNF-α/IL-10比值降低,躁动程度及发生率降低,镇静评分升高(P＜0.05);与DEX组和DEZ组比较,DEX+ DEZ组T2-4时血浆CRP、TNF-α浓度降低,IL-10浓度升高,TNF-α/IL-10比值降低,躁动程度及发生率降低(P＜0.05).四组患者苏醒期均无低血压、心动过缓、呼吸抑制、恶心呕吐等发生.结论 右美托咪定、地佐辛单独或复合用药均可降低开胸术患者苏醒期躁动程度及发生,同时可抑制炎性反应,且二者复合较单独用药效果更佳.     

基因组学技术在机械通气相关性肺损伤基因活化中的应用

机械通气是临床广泛应用的通气方式,它大大增加了重危患者抢救的成功率。然而,不合理的应用也可能产生和加重原有肺损伤,引起机械通气相关性肺损伤（VILI）。目前,VILI的基因表达及基因产物研究取得了很大进展,如早期诱导基因活化、临床敏感基因定位、基因信号传导通路等。而探讨基因组学技术在VILI中病理生理机制的应用,丰富和完善VILI理论,并为VILI提供有效的药物治疗方法。通过识别VILI中的相关因素,我们可利用其对VILI的危险人群进行识别。随着VILI的学科机制的完善与发展,关于VILI发病机制的完整性描述将会成为可能。     

Effect of complement C1q expression on hepatic ischemia-reperfusion injury in rats

Summary： The effect of the complement Clq expression on total hepatic ischemia-reperfusion （I/R） injury in rats was investigated. Sixty healthy male Sprague Dawley （SD） rats weighing 180-200 g were randomly divided into 5 groups： sham-operation group （S group, n=12）; group of I/R for 1 h （FR 1 h group, n=12）; group of I/R for 3 h （I/R 3 h group, n=12）; group of I/R for 6 h （I/R 6 h group, n=12）; group of UR for 24 h （I/R 24 h group, n=12）. The hepatic I/R model of rats was established, and liver tissues were obtained 1 h, 3 h, 6 h and 24 h after hepatic I/R, respectively. Furthermore, the tissues were stained using hematoxylin-eosin, and the liver injuries of rats were observed using a microscope. The malondialdehyde （MDA） level and superoxide dismutase （SOD） activity in liver tissue were determined Real-time polymerase chain reaction （PCR） and Western blotting were used to detect the expression levels of Clq mRNA and protein, respectively. As compared with the S group, the histopathological changes in I/R 1 h-24 h groups were gradually aggravated with the extension of FR time. As compared with the S group, SOD activity and MDA content in the I/R groups were reduced and increased respec- tively with the extension of UR time （P〈0.01）. Furthermore, the Clq expression at mRNA and protein levels in the I/R groups （especially in the I/R 3 h group） was significantly higher than that in the S group （P〈0.05）. It is suggested that Clq expression may play a principal role in hepatic I/R injury, particularly at the early stage ofperfusion.     

Effect of TLR-4 and HO-1 on acute lung injury induced by hemorrhagic shock in mice

Objective： To examine whether TLR-4 has an ettect on hemorrhage induced changes in lung, and to investigate the change of heme oxygenase-1 （HO-1） on acute lung injury （ALl） induced by hemorrhagic shock in mice.
Methods： Forty-eight male mice, including C3H/HeN mice and C3H/HeJ mice, were randomly divided into sham group （n=12）, hemorrhagic shock group with twelve mice in each phase. Blood pressure （BP） was monitored continuously by attaching carotid artery catheter to a strain gauge pressure transducer/ polygraph. Arterial blood samples were taken for blood gas analysis. A mouse model of non-lethal hemorrhagic shock and resuscitation was used to observe pulmonary myeloperoxidase （MPO） activity and wet/dry weight ratio （W/D）. The expression of HO- 1 was observed by means of RT-PCR and immunohistochemistry. IL-6 and IL-10 in lung tissue homogenate were assayed by enzyme-linked immunosorbent assay （ELISA）. The pulmo- nary pathologic changes were observed under electron microscope and light microscope.
Results： Compared with sham group, the expression of HO- 1 in lung tissue was significantly higher in Hem 24 h and Hem 48 h of C3H/HeN mice （P〈0.01）. The expression of HO-1 mRNA and the levels of IL-6, IL-10 and MPO in lung tissue were markedly increased in Hem 24 h （P〈0.01 or P〈0.05）; Compared with C3H/HeN mice, the expression of HO- 1 rnRNA and the levels of IL-6 and IL-10 in C3H/HeJ mice significantly decreased in Hem 24 h and Hem 48 h （P〈0.01 or P〈O.05）, and the W/D, MPO in C3H/HeJ mice were obvi- ously lower in Hem 24 h （P〈0.05）. The injuries of lung tissues after hemorrhagic shock have been demonstrated by histological examination with electron microscope and light microscope.
Conclusions： TLR-4 and HO-1 might modulate the bal- ance of pro- and anti-inflammatory processes in inflamma- tory reaction of hemorrhagic shock-induced ALl, and the activation of Toll-like receptor might induce the transcrip- tion activity of HO- 1, which may play a k     

盐酸戊乙奎醚对脓毒症小鼠肺血管内皮细胞黏附分子-1和髓过氧化物酶影响

目的:探讨盐酸戊乙奎醚(PHC)对脓毒症小鼠肺组织血管内皮细胞黏附分子-1(VCAM-1)水平、髓过氧化物酶(MPO)活性和β抑制蛋白-1(β-arrestin-1)表达的影响。方法:建立脓毒症小鼠模型,实验动物随机分为假手术组、盲肠结扎穿孔模型组(CLP组)和盐酸戊乙奎醚组(PHC组),每组10只。各组小鼠于造模12h时间点采血检测血乳酸水平,收集肺组织检测VCAM-1水平、MPO活性和β-arrestin-1mRNA的表达。结果:与假手术组比较,CLP组血乳酸值、肺VCAM-1水平和MPO活性升高,β-arrestin-1mRNA表达降低;与CLP组比较,PHC组可降低血乳酸值、肺VCAM-1水平和MPO活性,而增加β-arrestin-1mRNA表达。结论:盐酸戊乙奎醚预处理,可以通过上调β-arrestin-1的表达,从而降低VCAM-1水平和MPO活性,减轻脓毒症小鼠肺损伤。     

电针足三里对严重烫伤致大鼠急性肺损伤的影响

目的 探讨电针足三里对严重烫伤致大鼠急性肺损伤的影响.方法 雄性SD大鼠40只,体重200～250 g,随机分为5组(n=8):对照组、烫伤组、足三里组、非经非穴组和α-银环蛇毒素组(α-BGT组).对照组尾静脉注射生理盐水1 ml.烫伤组、足三里组、非经非穴组和α-BGT组先制备30%总体表面积Ⅲ度烫伤模型,然后烫伤组尾静脉注射生理盐水1 ml;足三里组于双侧足三里穴垂直进针7 mm,给予脉冲电流(电压3V,电流2ms,频率3 Hz)持续刺激12 mim,间隔8 h刺激1次,持续2 d;非经非穴组于双侧足三里穴旁5mm处给予脉冲刺激,方法同足三里组;α-BGT组尾静脉注射α-BGT 1.0 μg/kg,再于双侧足三里穴给予脉冲刺激,方法同足三里组.各组处理结束后,处死大鼠,取肺组织,光镜下观察病理学结果,电镜下观察超微结构,采用ELISA法测定肺组织高迁移率族蛋白B1(HMGBl)含量,采用免疫组化法测定HMGBl蛋白表达,采用RT-PCR法测定HMGBl mRNA表达.结果 烫伤组肺组织光镜下可见肺泡壁崩解,泡内大量渗出液,间质水肿、肥厚和增生,伴大量炎性细胞浸润;电镜下可见细胞核形态不规则,核膜僵硬,部分凸凹不平和核溶解,胞质内板层小体明显减少,肺组织病理损伤程度较对照组减轻.与对照组比较,烫伤组、非经非穴组和α-BGT组肺组织HMGBl含量升高,HMGBl蛋白及其mRNA的表达上调(P<0.05),足三里组各指标差异无统计学意义(P>0.05);与烫伤组比较,足三里组肺组织HMGBl含量降低,HMGBl蛋白及其mRNA的表达下调,非经非穴组和α-BGT组肺组织HMGBl mRNA表达下调(P<0.05);与足三里组比较,非经非穴组和α-BGT组肺组织HMGBl含量升高,HMGBl蛋白及其mRNA的表达上调(P<0.05).结论 电针足三里可减轻严重烫伤致大鼠急性肺损伤,其机制与激活含α7亚基N型胆碱能受体介导的胆碱能抗炎通路,抑制肺组织HMGBl的表达有关.     

乳化异氟烷对兔心肌缺血-再灌注损伤的作用

目的 探讨乳化异氟烷预处理对心肌缺血再灌注损伤的保护作用.方法 雄性新西兰兔32只,体重2.0～2.5 kg,随机分成4组(n=8):心肌缺血再灌注组(对照组,C组)、脂肪乳组(L组)、异氟烷组(I组)和乳化异氟烷组(EI组).每组均缺血1 h,再灌注3 h.实验结束后测定血清磷酸肌酸激酶(CK)和乳酸脱氢酶(LDH)活性,电镜观察心肌组织超微结构的变化.所有数据以均数±标准差(-x±s)表示,采用单因素方差分析,并用Dunnett检验进行两两比较,差异有统计学意义(P＜0.05).结果 与C组比较,I组和EI组血清CK和IDH降(P＜0.05),而L组无明显变化.电镜下C组和L组线粒体水肿,破坏明显,而I组和EI组线粒体损伤较轻.结论 乳化异氟烷预先给药体对兔心肌缺血再灌注损伤有明显的保护作用.     

术后谵妄大鼠血脑脊液屏障的变化

目的:评价术后谵妄大鼠血脑脊液屏障的变化。方法:SPF级健康雌性SD大鼠147只,3月龄,体重240～300 g,采用随机数字表法分成3组( n＝49)：对照组(C组)、单纯麻醉组(A组)和术后谵妄组(P组)。C组大鼠不接受麻醉和手术处理,A组大鼠接受1.4%异氟烷麻醉2 h处理,P组大鼠在1.4%异氟烷麻...