吸入一氧化氮对脂多糖所致大鼠急性肺损伤环氧合酶-2及TOLL样受体4表达的影响

目的 建立脂多糖致大鼠急性肺损伤的模型,观察一氧化氮对大鼠气道环氧合酶-2(cox-2)和Toll样受体4(TLR4)的分布及表达的影响.方法 健康雄性SD大鼠24只,按随机数字表法分为正常对照组、单用脂多糖(脂多糖组)、脂多糖加NO 20×10-6mg/L(低浓度NO组),脂多糖加NO 100×10-6mg/L(高浓度NO组).气管内滴注脂多糖(5 mg/kg)建立大鼠急性肺损伤模型.观察6 h后的肺水肿程度、免疫组织化学(SP染色)和实时荧光定量PCR检测肺组织中COX-2和TLR4的表达,以及分别吸入20×10-6、100×10-6mg/L浓度NO后的影响.所得数据采用单因素方差分析进行统计学分析,多个样本均数之间的两两比较采用LSD-t检验.结果 COX-2和TLR4在对照组大鼠气道内有广泛的分布和表达.脂多糖组大鼠肺水肿程度明显高于对照组,其主支气管和肺内细支气管上皮细胞内COX-2(6.5±2.8)及TLR4(44.9±11.3)表达高于对照组(分别为2.8 4±0.8、2.1±0.7),差异有统计学意义(t值分别为3.003、10.480,均P<0.01).低浓度NO组肺水肿程度明显减轻,其COX-2表达量(5.0±2.0)低于脂多糖组,但差异无统计学意义(t=1.227,P>0.05).而低浓度NO组TLR4(16.2±3.8)的表达量与脂多糖组(44.9±11.3)比较差异具有统计学意义(t=7.030,P<0.001).结论 COX-2和TLR4在大鼠气道内广泛分布,脂多糖刺激可使COX-2和TLR4的表达增强,吸入适当浓度NO可降低由脂多糖引起的COX-2和TLR4表达的增高.     

急性呼吸窘迫综合征机械通气进展

机械通气是急性呼吸窘迫综合征(ARDS)治疗的主要措施,然而机械通气本身具有一些严重的副作用,尤其是呼吸机所致肺损伤,甚至成为造成ARDS患者死亡的主要因素。近年来人们对ARDS病理解剖、病理生理进行了大量的研究,并在此基础上对机械通气模式做了较多改进,在实验研究和临床研究中均取得了令人鼓舞的效果,使ARDS病死率明显降低。本文对近10年来机械通气方面的进展综述如下。     

神经调节辅助通气对急性呼吸窘迫综合征兔呼吸机相关性膈肌功能障碍的影响

目的 探讨神经调节辅助通气(NAVA)对ARDS呼吸机相关性膈肌功能障碍(VIDD)的预防作用.方法 将20只成年新西兰大白兔按随机数字表法分为对照组、容量控制通气组(VC组)、压力支持通气组(PSV组)和NAVA通气组(NAVA组),每组5只.VC、PSV及NAVA组在机械通气4 h后取膈肌标本,对照组麻醉后立即取膈肌标本.测定各组膈肌中丙二醛、超氧化物歧化酶(SOD)以及还原型谷胱甘肽(GSH)含量,观察各组膈肌纤维病理结构的改变.结果 (1)丙二醛:NAVA组膈肌中丙二醛含量为(0.28±0.19)nmol/mg,与对照组的(0.15±0.06)nmol/mg、PSV组的(0.30±0.11)nmol/mg比较,差异无统计学意义(F=2.730,P＞0.05);VC组膈肌中丙二醛含量为(0.40±0.16)nmol/mg,明显高于对照组(P＜0.05).(2)SOD:NAVA组膈肌中SOD含量为(94±9)U/mg,与对照组的(111±12)U/mg、PSV组的(93±4)U/mg比较,差异无统计学意义(F=4.422,P＞0.05);VC组膈肌中SOD含量为(80±21)U/mg,明显低于对照组(P＜0.05).(3)GSH:NAVA组膈肌中丙二醛含量为(5.6±1.0)mg/g,与对照组的(5.3±1.0)mg/g、PSV组的(4.5±1.2)mg/g比较,差异无统计学意义(F=3.001,P＞0.05);VC组膈肌中GSH含量为(3.3±1.7)mg/g,明显低于对照组(P＜0.05).(4)光镜观察:VC组出现肌纤维变性、坏死,部分肌纤维萎缩;NAVA、PSV组以及对照组肌纤维形态基本正常.(5)电镜观察:VC组肌原纤维断裂,线粒体肿胀;NAVA组、PSV组以及对照组超微结构无明显异常.(6)膈肌纤维横截面积:NAVA组平均肌纤维横截面积(像素)为2573±278,与对照组的3070+175、PSV组的2508±670比较,差异无统计学意义(F=1.775,P＞0.05);VC组Ⅱ型肌纤维横截面积为2210±971,明显低于对照组的3477±187(P＜0.05).结论 与控制通气相比较,NAVA可减轻ARDS膈肌氧化应激、膈肌萎缩和膈肌结构损伤,NAVA较控制通气更能预防VIDD.

Abstract：

Objective To evaluate the effect of neurally adjusted ventilatory assist (NAVA) on prevention of ventilator-induced diaphragmatic dysfunction (VIDD) in ARDS rabbits.Methods Twenty New Zealand white rabbits were randomly divided into 4 groups: ( 1 ) control group ( n = 5 ); ( 2 ) Volume control (VC) group ( n = 5 ); ( 3 ) Pressure support ( PSV ) group ( n = 5 ); (4) NAVA group ( n = 5 ).In VC, PSV and NAVA groups, the rabbits were killed and the diaphragm was removed after 4 hours of ventilation.Animals in the control group were not mechanically ventilated, and the diaphragm was also removed immediately after anesthetizing.In all rabbits, malondialdehyde ( MDA), superoxide disrmutase (SOD) and glutathione(GSH) of diaphragm were measured.Structure of diaphragm was observed by light microscope, electron microscope, constituent ratio and mean cross-sectional area (CSA) of diaphragm fiber.Results (1)MDA: Compared with the control [(0.15 ±0.06)nmol/mg], PSV group[(0.30 ±0.11)nmol/mg], there was no significant difference in MDA of diaphragm in NAVA group [( 0.28 ± 0.19 )nmol/mg] (F = 2.730, P ＞ 0.05).MDA in VC group [(0.40 ±0.16)nmol/mg] was significantly higher than the control group (P＜0.05).(2) SOD: Compared with control [( 111 ± 12) U/mg], PSV group [(93 ± 4) U/mg], there was no significant difference in SOD of diaphragm in NAVA group [( 94 ± 9 )U/mg] (F=4.422,P ＞0.05).SOD in VC group [(80 ±21 )U/mg] was significantly lower than the control group(P ＜0.05).(3)GSH: Compared with control [(5.3 ± 1.0)mg/g] and PSV group [(4.5 ±1.2)mg/g], there was no significant difference in GSH of diaphragm in NAVA group [(5.6 ± 1.0) mg/g](F =3.001 ,P ＞ 0.05 ).GSH in VC group [(3.3 ± 1.7)mg/g] is significantly lower than control and NAVA groups ( P ＜ 0.05 ).( 4 ) Light microscope: In VC group, many changes were observed in the muscle, such as myofibrosis, necrosis, and some of muscle fibers became atrophy, but these were no obvious changes of pathological structure in control, PSV or NAVA groups.(5)Electron microscope: In control, PSV and NAVA groups, the ultrastructure of diaphragm was normal Different from the above 3 groups, some abnormal ultrastructure was observed in VC group, including disrupted myofibrils, swollen mitochondria.(6)CSA of diaphragm fiber: Compared with control and PSV group, there was no significant difference in CSA of diaphragm fiber in NAVA group ( P ＞ 0.05 ); The CSA of type Ⅱ fibers in VC group was markedly lower than control group ( P ＜ 0.05 ) .Conclusions Compared with volume control ventilation, NAVA may mitigate diaphragmatic oxidative stress, atrophy and injury, and prevent VIDD better than VC.     

神经调节辅助通气对急性呼吸窘迫综合征兔呼吸机相关性膈肌功能障碍的影响

Objective To evaluate the effect of neurally adjusted ventilatory assist (NAVA) on prevention of ventilator-induced diaphragmatic dysfunction (VIDD) in ARDS rabbits.Methods Twenty New Zealand white rabbits were randomly divided into 4 groups: ( 1 ) control group ( n = 5 ); ( 2 ) Volume control (VC) group ( n = 5 ); ( 3 ) Pressure support ( PSV ) group ( n = 5 ); (4) NAVA group ( n = 5 ).In VC, PSV and NAVA groups, the rabbits were killed and the diaphragm was removed after 4 hours of ventilation.Animals in the control group were not mechanically ventilated, and the diaphragm was also removed immediately after anesthetizing.In all rabbits, malondialdehyde ( MDA), superoxide disrmutase (SOD) and glutathione(GSH) of diaphragm were measured.Structure of diaphragm was observed by light microscope, electron microscope, constituent ratio and mean cross-sectional area (CSA) of diaphragm fiber.Results (1)MDA: Compared with the control [(0.15 ±0.06)nmol/mg], PSV group[(0.30 ±0.11)nmol/mg], there was no significant difference in MDA of diaphragm in NAVA group [( 0.28 ± 0.19 )nmol/mg] (F = 2.730, P ＞ 0.05).MDA in VC group [(0.40 ±0.16)nmol/mg] was significantly higher than the control group (P＜0.05).(2) SOD: Compared with control [( 111 ± 12) U/mg], PSV group [(93 ± 4) U/mg], there was no significant difference in SOD of diaphragm in NAVA group [( 94 ± 9 )U/mg] (F=4.422,P ＞0.05).SOD in VC group [(80 ±21 )U/mg] was significantly lower than the control group(P ＜0.05).(3)GSH: Compared with control [(5.3 ± 1.0)mg/g] and PSV group [(4.5 ±1.2)mg/g], there was no significant difference in GSH of diaphragm in NAVA group [(5.6 ± 1.0) mg/g](F =3.001 ,P ＞ 0.05 ).GSH in VC group [(3.3 ± 1.7)mg/g] is significantly lower than control and NAVA groups ( P ＜ 0.05 ).( 4 ) Light microscope: In VC group, many changes were observed in the muscle, such as myofibrosis, necrosis, and some of muscle fibers became atrophy, but these were no obvious changes of pathological structure in control, PSV or NAVA groups.(5)Electron microscope: In control, PSV and NAVA groups, the ultrastructure of diaphragm was normal Different from the above 3 groups, some abnormal ultrastructure was observed in VC group, including disrupted myofibrils, swollen mitochondria.(6)CSA of diaphragm fiber: Compared with control and PSV group, there was no significant difference in CSA of diaphragm fiber in NAVA group ( P ＞ 0.05 ); The CSA of type Ⅱ fibers in VC group was markedly lower than control group ( P ＜ 0.05 ) .Conclusions Compared with volume control ventilation, NAVA may mitigate diaphragmatic oxidative stress, atrophy and injury, and prevent VIDD better than VC.     

溃疡性结肠炎患者外周血TLR4、NLRP3炎性小体表达与疾病转归的关系分析

目的 探讨溃疡性结肠炎(UC)患者外周血Toll样受体4(TLR4)、NOD受体蛋白3(NLRP3)炎性小体表达与疾病转归的关系。方法 选取2019年6月至2021年6月收治的95例UC患者作为研究对象,根据病情严重程度分为轻度组(n=53)、中度组(n=26)和重度组(n=16),另选取同期健康体检者40例作为对照组,比较4组外周血TLR4、NLRP3炎性小体表达,并分析其与疾病转归的关系。结果 重度组外周血TLR4、NLRP3、ASC、caspase-1表达高于中度组、轻度组和对照组(P<0.05)。转归组外周血TLR4、NLRP3、ASC、caspase-1表达低于未转归组(P<0.05);ROC曲线显示,TLR4、NLRP3、ASC、caspase-1联合预测疾病转归的AUC为0.923,高于TLR4的0.766、NLRP3的0.711、ASC的0.754、caspase-1的0.763(Z=2.687、3.614、2.699、2.688,P均<0.05);多因素回归分析显示,TLR4表达>8.76、NLRP3表达>4.09、ASC表达>12...     

压力支持通气模式下呼气触发灵敏度对急性呼吸窘迫综合征患者呼吸效率的影响

目的探讨压力支持通气(PSV)模式下呼气触发灵敏度(ETS)对急性呼吸窘迫综合征(ARDS)患者呼吸力学指标的影响。方法选取2012年我院重症监护室收治的需行有创机械通气的ARDS患者31例,分别测定ETS在5%、25%、45%水平下对患者呼吸频率(RR)、潮气量(Vt)、每分钟通气量(VE)、吸呼比(IBE)、呼气时间(Te)、吸气时间(Ti)、呼气流速(Exp Flow)、吸气流速(Insp Flow)、浅快呼吸指数(RSB)、呼气阻力(R exp)、吸气阻力(R insp)、动态肺顺应性(C)等参数的影响。结果随着ETS逐渐增加,Vt、Ti、IBE、Exp Flow、C逐渐下降,RR、R exp、RSB逐渐升高(P0.05)。结论在临床工作中,对于需要进行机械通气的患者,应选择适宜的ETS。     

丹参酮ⅡA 对急性肺损伤小鼠气道炎症抑制作用研究

目的：研究丹参酮ⅡA (TⅡA)对 ALI 小鼠气道炎症的抑制作用。方法用脂多糖(LPS)刺激 C57小鼠,建立 ALI 的动物模型,同时用 TⅡA 进行干预,实验共分为四组：正常对照组、LPS 组、TⅡA 组和 TⅡA+LPS 组,HE 染色观察各组小鼠 BALF 中炎性细胞的分布变化并对细胞进行分类计数,聚合酶链反应(PCR)及酶联免疫吸附测定(ELISA)等方法观检测 TⅡA 对 ALI小鼠肺组织及 BALF 中 Muc5AC、肿瘤坏死因子α(TNF-α)表达水平的影响;结果正常对照小鼠BALF 中淋巴细胞占绝大多数,单独给予 T Ⅱ A 对 BALF 细胞分布无影响,LPS 所致的 ALI 小鼠BALF 中炎性细胞总数明显增加,且以中性粒细胞占多数,TⅡA 能够明显抑制 ALI 小鼠 BALF 中炎性细胞总数及中性粒细胞数;TⅡA 能够明显抑制 ALI 小鼠 BALF 中气道黏蛋白 Muc5AC 及 TNF-α的表达水平。结论 TⅡA 能够明显抑制 ALI 小鼠气道炎症水平。     

心房钠尿肽对急性肺损伤SD大鼠肺泡灌洗液中乳酸脱氢酶和总蛋白及总磷脂含量的影响

目的分析心房钠尿肽急性肺损伤SD大鼠肺泡灌洗液中乳酸脱氢酶和总蛋白及总磷脂的影响。方法选择成年SD大鼠21只,把它们随机分为对照组、脂多糖模型组和心房钠尿肽治疗组。所有SD大鼠通过颈外静脉注射,在给药4h后处死并收集它们的肺泡灌洗液,测定肺泡灌洗液的乳酸脱氢酶、总蛋白含量及总磷脂含量。结果心房钠尿肽组与脂多糖模型组比较,乳酸脱氢酶及总磷脂含量明显下降、总蛋白含量明显提高,差异有统计学意义(P<0.05)。结论心房钠尿肽能够减轻脂多糖引发的急性肺损伤。     

急性呼吸窘迫综合征机械通气患者早期肠内营养支持治疗的临床疗效观察

目的探讨早期肠内营养支持治疗急性呼吸窘迫综合征机械通气患者的疗效。方法选取2011年1月—2012年8月我科76例急性呼吸窘迫综合征机械通气患者,将其随机分为两组。对照组给予常规治疗及早期胃肠减压,并在入院48h后停用胃肠减压,开始经胃管肠内营养;观察组给予常规治疗及早期(入院24h内)肠内营养。观察治疗前后两组患者血清蛋白、血红蛋白、氮平衡、免疫球蛋白(IgG、IgM)、7d脱机率。结果观察组治疗后血清蛋白、血红蛋白、氮平衡、免疫球蛋白、7d脱机率均优于对照组,差异有统计学意义(P<0.05)。结论急性呼吸窘迫综合征机械通气患者早期应用肠内营养支持治疗可改善营养状况,提高脱机成功率。     

呼吸机相关肺损伤兔细胞间黏附分子-1和白细胞介素-10的表达及激活蛋白-1活性的变化

目的 研究呼吸机相关肺损伤(VILI)兔细胞间黏附分子-1(ICAM-1)、白细胞介素(IL)-10的表达及激活蛋白-1(AP-1)DNA结合活性的变化,并探讨其在VILI炎症反应中的意义.方法 应用40 ml/kg的大潮气量(VT)机械通气建立兔VILI模型.将40只新西兰兔按随机数字表法分为非机械通气对照组、常规VT组、大VT 1h组、大VT 2 h组及大VT 4 h组.用酶联免疫吸附法(ELISA)检测肺组织匀浆可溶性细胞间黏附分子-1(sICAM-1)和IL-10含量,逆转录多聚酶链反应(RT-PCR)检测mRNA表达.凝胶电泳迁移率分析法(EMSA)测定AP-1的活性,同时测定PaO2、髓过氧化物酶(MPO)、肺湿重/干重比值(W/D).结果 (1)肺组织匀浆中sICAM-1含量:大VT2 h组[(23±5)ng/L]及大VT 4 h组[(35±5)ng/L]均高于常规VT组[(16±4)ng/L],均P＜0.05;大VT4 h组高于大VT 1 h组[(19±4)ng/L]及大VT 2 h组(均P＜0.01).肺组织匀浆IL-10含量:大VT2 h组[(24±4)ng/L]和大VT4 h组[(26±5)ng/L]均高于常规VT组[(15±2)ng/L,均P＜0.05],大VT4 h组高于大VT 1 h组[(19±4)ng/L,P＜0.05].ICAM-1 mRNA含量:大VT 2 h组(1.18±0.19)及大VT4 h组(1.29±0.19)均高于常规VT组(0.84±0.13,均P＜0.05).大VT4 h组高于大VT1 h组(0.96±0.24,P＜0.05).IL-10 mRNA含量:大VT 4 h组(1.13±0.17)高于常规VT组(0.84±0.20)和大VT 1 h组(0.86±0.12,均P＜0.05).(2)AP-1的DNA结合活性:大VT 2 h组(34±8)和大VT4 h组(38±9)均高于常规VT组(23±9,均P＜0.01),大VT4 h组高于大VT 1 h组(25±9,P＜0.01).(3)病理学检查显示大VT机械通气后随时间延长肺损伤逐渐加重,大VT机械通气2 h可见MPO升高,4 h可见PaO2下降及W/D升高.结论 ICAM-1、IL-10参与了VILI的炎症反应过程,二者升高可能与其mRNA的表达增高有关.核转录因子AP-1可能参与了上述炎性介质基因的转录调节.     

Flagellin-induced NLRC4 phosphorylation primes the inflammasome for activation by NAIP5

The Nlrc4 inflammasome contributes to immunity against intracellular pathogens that express flagellin and type III secretion systems, and activating mutations in NLRC4 cause autoinflammation in patients. Both Naip5 and phosphorylation of Nlrc4 at Ser533 are required for flagellin-induced inflammasome activation, but how these events converge upon inflammasome activation is not known. Here, we showed that Nlrc4 phosphorylation occurs independently of Naip5 detection of flagellin because Naip5 deletion in macrophages abolished caspase-1 activation, interleukin (IL)-1β secretion, and pyroptosis, but not Nlrc4 phosphorylation by cytosolic flagellin of Salmonella Typhimurium and Yersinia enterocolitica. ASC speck formation and caspase-1 expression also were dispensable for Nlrc4 phosphorylation. Interestingly, Helicobacter pylori flagellin triggered robust Nlrc4 phosphorylation, but failed to elicit caspase-1 maturation, IL-1β secretion, and pyroptosis, suggesting that it retained Nlrc4 Ser533 phosphorylating-activity despite escaping Naip5 detection. In agreement, the flagellin D0 domain was required and sufficient for Nlrc4 phosphorylation, whereas deletion of the S. Typhimurium flagellin carboxy-terminus prevented caspase-1 maturation only. Collectively, this work suggests a biphasic activation mechanism for the Nlrc4 inflammasome in which Ser533 phosphorylation prepares Nlrc4 for subsequent activation by the flagellin sensor Naip5.Inflammasomes contribute critically to immunity and antimicrobial host defense of mammalian hosts. Their activation is tightly controlled because aberrant inflammasome signaling is harmful to the host, and results in inflammatory diseases (1, 2). Inflammasomes are a set of cytosolic multiprotein complexes that recruit and activate caspase-1, a key protease that triggers secretion of the inflammatory cytokines interleukin (IL)-1β and IL-18. In addition, caspase-1 induces pyroptosis, a proinflammatory and lytic cell death mode that contributes to pathogen clearance (3, 4). Several inflammasomes respond to a distinctive set of microbial pathogens (5). Activating mutations in the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) member Nlrc4 were recently shown to induce autoinflammation in patients (6–8). Moreover, the inflammasome assembled by Nlrc4 is critically important for clearing a variety of bacterial infections, including Salmonella enterica serovar Typhimurium (S. Typhimurium), Shigella flexneri, Pseudomonas aeruginosa, Burkholderia thailandensis, and Legionella pneumophila (3, 9–17). These intracellularly-replicating bacteria have in common that they propel themselves with flagella (18) and/or express bacterial type III secretion systems (T3SS) to translocate effector proteins into infected host cells (19). Members of the NLR apoptosis-inhibitory protein (Naip) subfamily recognize the cytosolic presence of the building blocks of these evolutionary conserved bacterial structures, and trigger Nlrc4 to assemble an inflammasome (20–25). C57BL/6J mice express four Naip proteins, Naip1, -2, -5, and -6, which are expressed from a multigene cluster located on chromosome 13qD1 (26). Mouse Naip1 and human NAIP bind T3SS needle proteins, Naip2 interacts with the T3SS basal rod component PrgJ, and Naip5 and Naip6 recognize flagellin (20, 22–25).In addition to these Naip sensors, recent work showed that phosphorylation of Nlrc4 at Ser533 is critical for activation of the Nlrc4 inflammasome following infection with S. Typhimurium and L. pneumophila, or transfection of purified S. Typhimurium flagellin (27). Reconstitution of immortalized Nlrc4^−/− macrophages with wild-type Nlrc4 restored S. Typhimurium- and L. pneumophila-induced inflammasome activation, whereas cells reconstituted with Nlrc4 S533A mutant were specifically defective in maturation of caspase-1, secretion of IL-1β, assembly of ASC (apoptosis-associated speck-like protein containing a CARD) specks and induction of pyroptosis by these pathogens (27). However, a central outstanding question is how these upstream events (i.e., bacterial recognition by Naip members and Nlrc4 phosphorylation) relate to each other. Naip binding of bacterial components may trigger Nlrc4 phosphorylation to induce inflammasome activation. Alternatively, Nlrc4 phosphorylation and Naip sensing of flagellin and T3SS may converge independently onto Nlrc4 inflammasome activation.Here, we approached this question by breeding Nlrc4^Flag/Flag mice that express Nlrc4 fused to a carboxy-terminal 3× Flag tag from both Nlrc4 alleles (27) with Naip5-deficient mice (22, 28). We found S. Typhimurium infection and cytosolic delivery of S. Typhimurium flagellin, S. Typhimurium PrgJ and Yersinia enterocolitica flagellin to induce Nlrc4 phosphorylation at Ser533 independently of Naip5. Interestingly, Helicobacter pylori (H. pylori) flagellin induced robust Nlrc4 Ser533 phosphorylation without caspase-1 activation, suggesting that Nlrc4 Ser533 phosphorylation and caspase-1 activation are molecularly decoupled. In agreement, the S. Typhimurium flagellin D0 domain was required and sufficient for Nlrc4 phosphorylation, whereas caspase-1 activation required the flagellin carboxy-terminus. Collectively, this work suggests a biphasic activation mechanism for the Nlrc4 inflammasome in which Ser533 phosphorylation primes Nlrc4 for subsequent activation by the flagellin sensor Naip5.     

两种通气方法对健康及急性肺损伤犬心肺功能影响的比较研究

目的比较双水平压力调节（ＢｉＰＡＰ）通气和间歇正压通气（ＩＰＰＶ）对心肺功能的影响。方法在两种通气模式０、０．５、１ｋＰａ呼气末压（ＥＥＰ）时分别测定健康犬及油酸诱发急性肺损伤犬的呼吸力学、血流动力学及血气分析各参数。结果无论有无急性肺损伤，ＢｉＰＡＰ通气在ＥＥＰ为０、０．５、１ｋＰａ时的气道平均压均低于ＩＰＰＶ时，但心输出量等血流动力学参数并无明显差异。另外在急性肺损伤时，ＢｉＰＡＰ通气时血氧分压（ＰａＯ２、ＰｖＯ２）均较ＩＰＰＶ时增高。结论与ＩＰＰＶ相比，ＢｉＰＡＰ通气能显著降低气道压力，在急性肺损伤时，可有效改善动脉血氧分压，但对血流动力学的影响两者无明显差异。     

神经电活动辅助通气对急性呼吸窘迫综合征患者人机同步性的影响

目的 观察神经电活动辅助通气(NAVA)对急性呼吸窘迫综合征(ARDS)患者人机同步性的影响.方法 以2008年1月至6月入住东南大学附属中大医院ICU 18例ARDS机械通气患者为研究对象,按随机数字表法选择NAVA或压力支持通气(PSV)模式进行通气,通气支持水平分4步递增.PSV压力支持水平从5 cm H2O(1 cm H2O=0.098 kPa)开始,每5 min增加5 cm H2O,分别为5、10、15、20 cm H2O.NAVA支持水平每5 min增加0.2～1.0 cm H2O/μY,使NAVA中通气支持水平分别与PSV 4个压力支持水平相当,观察不同支持条件下(PSV1～PsV4及NAVA1～NAVA4)人机同步性、呼吸肌负荷、血流动力学以及呼吸力学等指标.结果 (1)吸气触发:①触发延迟时间:随着支持水平增加,PSV中触发延迟时间明显延长(P<0.05),而应用NAVA通气时触发延迟时间无明显延长.与相同支持水平的PSV比较,应用NAVA的触发延迟时间均明显缩短(P<0.05).②无效触发:随着PSV支持水平增加,无效触发明显增加,PSV1时无效触发2.3%,PSV4时无效触发为22%(P<0.05).应用NAVA时,不同支持水平下,均未见无效触发.(2)吸/呼气转换:随着支持水平增加,PSV中吸/呼气转换延迟时间明显延长(P<0.05),而应用NAVA通气时吸/呼气转换延迟时间无明显延长.与相同支持水平的PSV比较.应用NAVA时吸/呼气转换延迟时间均明显缩短(P<0.05).(3)通气支持幅度(潮气量):PSV1和NAVA1的潮气量分别为(361±121)ml和(361±69)ml,差异无统计学意义.但NAVA3和NAVA4时的潮气量分别为(417±71)ml和(427±80)ml,明显低于PSV3和PSV4时的潮气量[分别为(604 ±141)ml和(675±108)ml,均P<0.05].(4)呼吸肌负荷:随着支持水平增加,应用NAVA和PSV通气的膈肌电活动幅度、食管压力时间乘积均逐渐降低(P<0.05).在相同支持水平时,两绢比较差异无统计学意义.结论 与PSV相比,NAVA通气支持时间、通气支持水平与自身呼吸形式更加匹;配,应用NAVA更能改善ARDS患者人机同步性.     

气道压力释放通气治疗急性呼吸窘迫综合征的研究进展

气道压力释放通气是一种兼具理论风险和效益的通气模式,常作为急性呼吸窘迫综合征和低氧血症患者的抢救或替代模式。因其具有保护性肺复张、保留自主呼吸、维持血流动力学稳定性、减少镇静及神经肌肉阻滞药物剂量、降低驱动压、增加平均气道压及降低呼吸机相关性肺损伤等诸多优点,越来越受到临床医师及研究者的关注。但不少学者对其有效性存在争议。本文就气道压力释放通气在急性呼吸窘迫综合征治疗中的最新研究进展作一综述。     

过氧化物酶增殖体激活受体-γ激动剂对急性肺损伤大鼠的保护作用及机制

目的 观察过氧化物酶增殖体激活受体-γ(PPAR-γ)激动剂对急性肺损伤大鼠的保护作用及其机制.方法 将72只Wistar大鼠按随机数字表法分为脂多糖组(32只)、曲格列酮干预组(32只)和对照组(8只).脂多糖组和曲格列酮干预组根据检测时间的不同再分为脂多糖及曲格列酮干预1、2、4、8 h组,每组各8只.脂多糖组静脉给予脂多糖(5 mg/kg),曲格列酮干预组在静脉注射脂多糖15 min后静脉给予曲格列酮(3 mg/kg).观察各组大鼠PaO2、肺组织髓过氧化物酶(MPO)活性、肺组织病理;采用RT-PCR法检测肺组织PPAR-γ、肿瘤坏死因子-γ(TNF-γ)mRNA表达;采用酶联免疫吸附法(ELISA)检测TNF-γ蛋白变化及用免疫组织化学观察肺组织PPAR-γ的改变;采用Western blot法测定肺组织核因子-γB(NF-γB)P65活性.采用SPSS 10.0软件进行统计学分析,各组间均数比较采用方差分析,均数两两比较采用q检验.结果 曲格列酮1、2、4、8 h组PaO2分别为(85±10)、(80±10)、(81±10)、(82±13)mm Hg(1 mm Hg=0.133 kPa),脂多糖组1、2.4、8 h组分别为(75±11)、(69±12)、(63±11)、(71±13)mm Hg,两组比较差异有统计学意义(F=4.32,P＜0.05);脂多糖2.4、8 h组MPO活性分别为(10.6±1.2)、(14.1±2.1)、(11.1±1.8)U/g,曲格列酮2、4、8 h组分别为(8.2±0.8)、(9.2±0.9)、(8.8±0.7)U/g,两组比较差异有统计学意义(F=14.99,P＜0.05);脂多糖1、2 h组肺组织TNF-γmRNA吸光度(A)值分别为0.68±0.07、0.92 ±0.05,曲格列酮1、2 h组分别为0.39±0.07、0.50±0.09,两组比较差异有统计学意义(q值分别为3.09、3.99,P＜0.05);脂多糖1、2 h组肺组织匀浆及血浆中TNF-?水平分别为(340±33)、(757±47)、(12.3±1.8)及(54.7±6.6)ng/L,曲格列酮1、2 h组为(306±30)、(685±47)、(10.0±1.7)及(46.8±5.9)ng/L,两组比较差异有统计学意义(q值分别为3.92、4.71、4.81、5.17,均P＜0.05);脂多糖1、2、4 h组肺组织PPAR-? mRNA表达(A值)分别为0.36±0.05、0.25±0.04、0.30±0.05,曲格列酮1、2.4 h干预组分别为0.39±0.02、0.44±0.05、0.46±0.04,两组比较差异有统计学意义(q值分别为6.13、5.69、3.72,均P＜0.05);脂多糖1、8 h组NF-?B P65由胞质向胞核移位(A值分别为0.81±0.14、1.91±0.16、0.33±0.06及2.01±0.18),曲格列酮1、8 h组分别为1.14±0.15、1.06±0.21、0.81±0.14、1.03±0.18,两组比较差异有统计学意义(q值分别为3.29、6.25、5.59、6.81,均P＜0.05).结论 在脂多糖诱发的大鼠急性肺损伤模型中,曲格列酮通过上调PPAR-γ表达来抑制NF-γB活性,使NF-γB调控的炎症介质表达下调,炎性细胞浸润和活化减少,从而保护肺组织.     

过氧化还原蛋白6对细菌脂多糖诱导的小鼠急性肺损伤氧化应激的保护作用

目的探讨过氧化还原蛋白Peroxiredoxin(Prdx)6对细菌脂多糖(LPS)诱导的小鼠急性肺损伤氧化应激的作用及机制。方法应用PCR法对Prdx6基因敲除小鼠行基因型鉴定并应用免疫组织化学法测定Prdx6蛋白在肺脏的表达。将雄性Prdx6基因敲除型小鼠（18只）按随机数字表法分入Prdx6敲除型对照组（9只）、Prdx6敲除型LPS 24 h组（9只）;将雄性野生型C57BL/6J小鼠（18只）按随机数字表法分入野生型对照组（9只）、野生型LPS 24 h组（9只）。各LPS组小鼠气管滴注LPS(5 mg/kg)制备急性肺损伤模型,于给药后24 h分别行肺脏病理检测,BCA法测定BALF内蛋白浓度,比色法测定肺脏总超氧化物歧化酶(T-SOD)活力和过氧化氢、羰基化蛋白和总抗氧化能力(TAOC),TBA法测定丙二醛的表达。结果Prdx6基因敲除小鼠肺组织免疫组织化学法未检测到Prdx6蛋白表达。两种属小鼠LPS组肺脏病理可见炎症细胞浸润、肺泡间隔增厚及肺泡内出血,Prdx6敲除型较野生型小鼠病理损伤更重。LPS刺激后,野生型LPS 24 h组BALF内的蛋白浓度为(441±54) mg/L,高于野生型对照组的(168±20) mg/L(t=-4.71,P＜0.01);Prdx6敲除型LPS 24 h组为(770±66)mg/L,高于野生型LPS 24 h组（t=-3.69,P＜0.01）。野生型LPS 24 h组T-SOD为(16.0±1.2) U/mg,低于野生型对照组的(26.5±3.9) U/mg(t=-6.22,P＜0.01);Prdx6敲除型LPS24 h组为(14.5±5.3)U/mg,与野生型LPS 24 h组差异无统计学意义（t=-0.56,P=0.60）。野生型LPS 24 h组肺脏过氧化氢和丙二醛[分别为(52.3±7.8)nmol/g和(3.3±0.5)nmol/mg]高于野生型对照组[分别为(29.5±3.2)nmok/g和(1.6±0.8)nmol/mg],差异有统计学意义（t值分别为-4.25和-5.94,均P＜0.01）,Prdx6敲除型LPS 24 h组[分别为(73.5±12.4)nmol/g和(5.9±0.9)nmol/mg],均高于野生型LPS24 h组（t值分别为-3.01和-6.01,均P＜0.05）。野生型LPS24 h组肺脏蛋白羰基为(6.9±1.2)nmol/mg,与野生型对照组的(6.1±0.9)nmol/mg差异无统计学意义(t=-1.62,P=0.15);Prdx6敲除型LPS 24 h组为(8.9±0.9)nmol/mg,高于野生型LPS 24 h组(t=-2.76,P＜0.05)。野生型LPS 24 h组肺脏TAOC为(4.7±0.6) U/mg,低于野生型对照组的(6.5±0.4) U/mg(t =3.35,P＜0.01);Prdx6敲除型LPS 24 h组为(3.9 ±0.4) U/mg,低于野生型LPS24 h组(t =2.44,P=0.04)。Prdx6敲除型对照组与其野生型对照组以上参数表达差异无统计学意义。结论在LPS诱导的肺损伤中,Prdx6基因缺失增加了活性氧的产生,加重了氧化应激反应,从而使肺损伤恶化。