高CO2血症对急性肺损伤时中性粒细胞功能的影响

急性肺损伤是一种具有高发病率和死亡率的临床疾病。尽管目前对其发病机制的认识不断深入，但临床上仍然没有寻找到可以有效控制其炎症损伤的方案。以往的研究表明，中性粒细胞是导致急性肺损伤时微血管及组织损伤的主要原因。目前，作为一种重要的保护性通气策略，高CO2血症除了可以减少机械通气导致的肺组织损伤以外，已经有越来越多的证据表明：高CO2血症具有抗炎以及抗氧化的作用。此文将主要论述急性肺损伤，中性粒细胞以及高CO2血症三者之间的关系。     

The effects of acute renal failure on long-term renal function

The relationship between acute renal failure (ARF) and long-term renal function remains unknown. We therefore undertook a study of patients at the Baltimore VA Hospital to examine the effects of a bout of acute renal injury on long-term renal function. We retrospectively reviewed the relationship between serum creatinine and time of observation for 6058 individuals who had values greater than 1.4 mg/dL in any two consecutive years. Individuals were stratified according to total years of observation with a minimum of two years. Severity of acute renal injury was divided into mild, moderate, and severe with elevations in baseline creatinine of < 50%, 50-300% and > 300% respectively. Sporadic elevations in creatinine were evident in 8-15% of the population. There were a total of 1328 episodes of acute renal failure in 916 patients that were suitable for analysis. Mild ARF on a substrate of normal or mildly abnormal renal function resolved without long-term sequelae. Moderate and severe ARF occurred more frequently on a background of reduced renal function but baseline function was retained in at least 60% of patients. We conclude that ARF is more frequent in patients with chronic kidney disease but it is not invariably associated with an accelerated course to end-stage renal disease or death. Overall, the majority of ARF events resolved without adverse long-term effects suggesting appropriate management in the majority of instances.     

In vitro and in vivo effects of salbutamol on neutrophil function in acute lung injury

BACKGROUND: Intravenous salbutamol (albuterol) reduces lung water in patients with the acute respiratory distress syndrome (ARDS). Experimental data show that it also reduces pulmonary neutrophil accumulation or activation and inflammation in ARDS. AIM: To investigate the effects of salbutamol on neutrophil function. METHODS: The in vitro effects of salbutamol on neutrophil function were determined. Blood and bronchoalveolar lavage (BAL) fluid were collected from 35 patients with acute lung injury (ALI)/ARDS, 14 patients at risk from ARDS and 7 ventilated controls at baseline and after 4 days' treatment with placebo or salbutamol (ALI/ARDS group). Alveolar-capillary permeability was measured in vivo by thermodilution (PiCCO). Neutrophil activation, adhesion molecule expression and inflammatory cytokines were measured. RESULTS: In vitro, physiological concentrations of salbutamol had no effect on neutrophil chemotaxis, viability or apoptosis. Patients with ALI/ARDS showed increased neutrophil activation and adhesion molecule expression compared with at risk-patients and ventilated controls. There were associations between alveolar-capillary permeability and BAL myeloperoxidase (r = 0.4, p = 0.038) and BAL interleukin 8 (r = 0.38, p = 0.033). In patients with ALI/ARDS, salbutamol increased numbers of circulating neutrophils but had no effect on alveolar neutrophils. CONCLUSION: At the onset of ALI/ARDS, there is increased neutrophil recruitment and activation. Physiological concentrations of salbutamol did not alter neutrophil chemotaxis, viability or apoptosis in vitro. In vivo, salbutamol increased circulating neutrophils, but had no effect on alveolar neutrophils or on neutrophil activation. These data suggest that the beneficial effects of salbutamol in reducing lung water are unrelated to modulation of neutrophil-dependent inflammatory pathways.     

The effects of prone positioning on intraabdominal pressure and cardiovascular and renal function in patients with acute lung injury

To detect any harmful effects of prone positioning on intraabdominal pressure (IAP) and cardiovascular and renal function, we studied 16 mechanically ventilated patients with acute lung injury randomly in prone and supine positions, without minimizing the restriction of the abdomen. Effective renal blood flow index and glomerular filtration rate index were determined by the paraaminohippurate and inulin clearance techniques. Prone positioning resulted in an increase in IAP from 12 +/- 4 to 14 +/- 5 mm Hg (P < 0.05), PaO(2)/fraction of inspired oxygen from 220 +/- 91 to 267 +/- 82 mm Hg (P < 0.05), cardiac index from 4.1 +/- 1.1 to 4.4 +/- 0.7 L/min (P < 0.05), mean arterial pressure from 77 +/- 10 to 82 +/- 11 mm Hg (P < 0.01), and oxygen delivery index from 600 +/- 156 to 648 +/- 95 mL. min(-)(1). m(-)(2) (P < 0.05). Renal fraction of cardiac output decreased from 19.1% +/- 12.5% to 15.5% +/- 8.8% (P < 0.05), and renal vascular resistance index increased from 11762 +/- 6554 dynes. s. cm(-)(5). m(2) to 15078 +/- 10594 dynes. s. cm(-)(5). m(2) (P < 0.05), whereas effective renal blood flow index, glomerular filtration rate index, filtration fraction, urine volume, fractional sodium excretion, and osmolar and free water clearances remained constant during prone positioning. Prone positioning, when used in patients with acute lung injury, although it is associated with a small increase in IAP, contributes to improved arterial oxygenation and systemic blood flow without affecting renal perfusion and function. Apparently, special support to allow free chest and abdominal movement seems unnecessary when mechanically ventilated, hemodynamically stable patients without abdominal hypertension are proned to improve gas exchange. IMPLICATIONS: Prone positioning is increasingly used to improve gas exchange in patients with acute lung injury. However, during prone positioning an increase in intraabdominal pressure in these critically ill patients may promote dysfunction of other organs. Therefore, we performed a randomized study in mechanically ventilated patients with acute lung injury to investigate the cardiovascular and renal effects of prone positioning.     

The effects of intratracheal dexamethasone on acute lung injury in rabbits--experimental study

BACKGROUND AND OBJECTIVE: The aim of our study was to investigate, in rabbits with hydrochloric (HCl) acid-induced Acute Lung Injury (ALI), the effects of intra-tracheal (i.t.) dexamethasone administration on neutrophil and platelet counts, plasma malonyl dialdehyde (MDA) level, histopathology, and arterial blood gases. METHODS: Twenty-eight New Zealand rabbits were randomly divided into a control (n = 14) and dexamethasone groups (n = 14). Anesthesia was applied with ketamine (50 mg kg(-1) h(-1), i.m.) and tracheostomy was performed. Both groups received 2 ml kg(-1) HCl (hydrochloric acid) i.t.. Five minutes later, 0.9% saline was given to the controls while the other group received i.t. dexamethasone. MDA levels of the plasma, neutrophil and platelet counts, and arterial blood gases were recorded at the beginning of the study and then at two and five hours. The rabbits were ventilated in pressure control mode for 5 hours. At the end of the study, the lungs were examined by light microscopy and the changes evaluated on a scale of 0 to 4. RESULTS: Neutrophil and platelets counts (p < 0.01) and PaO2 (p < 0.05) were greater in the dexamethasone group than the controls at five hours. Plasma MDA level (p < 0.01) and PaCO2 (p < 0.01) were greater in the control group. Histopathological changes were less severe in the dexamethasone group. CONCLUSION: Giving dexamethasone i.t. may have beneficial effects on the development of ALI.     

盐酸氨溴索预先给药对内毒素诱导大鼠急性肺损伤的作用

目的探讨盐酸氨溴索（AMB）预先给药对内毒素（LPS）诱导大鼠急性肺损伤（ALI）的作用及其机制。方法雄性SD大鼠108只，体重196～273g，12～14周龄。随机分为6组（n=18），A组生理盐水（NS）0．5ml腹腔注射（i．p．）1h后，再i．p．NS0．5ml；B组i．p．AMB 10mg／kg 1h后i．p．NS0．5ml；C组i.p．NS0．5ml 1h后i．p．LPS 5mg／kg；D、E、F组分别i．p．AMB5、10、20mg／kg后1hi．p．LPS5mg／kg。i．p．NS（A、B组）或LPS（C、D、E、F组）后1、2、4h各处死5只大鼠，采用双夹心抗体酶联吸附免疫法测定支气管肺泡灌洗液（BALF）中肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和巨噬细胞炎性蛋白-2（MIP-2）浓度，蛋白印迹法检测肺组织细胞胞浆中磷酸化／非磷酸化c—Jun氨基末端激酶（JNK）的表达。另外3只i．p．NS（A、B组）或LPS（C、D、E、F组）后4h观察大鼠肺组织形态学变化。结果与A组比较，C、D、E、F组BALF中TNF-α、IL-1β和MIP-2升高；与C组比较，E、F组上述三指标均降低。与A组比较，C、D、E、F组磷酸化JNK表达增多；与C组比较，E、F组磷酸化JNK表达减少，D、E、F组非磷酸化JNK表达增多（P〈0．05或0．01）。AMP预先给药可减轻i．p.LPS诱导的肺组织损伤。结论AMB预先给药可减轻LPS诱导大鼠ALI，其机制与抑制肺组织JNK的活化、下调TNF-α、IL-1β和MIP-2的表达有关．且呈剂量依赖性。     

肠内营养对重症胰腺炎患者免疫功能的影响

目的 研究肠内营养对重症胰腺炎患者免疫功能的影响。方法 对我院自2001～2002年32例重症胰腺炎病人行肠内营养(EN)的免疫球蛋白、细胞因子和红细胞免疫功能进行检测。并与30例采用肠外营养(TPN)的病人进行比较。结果 EN组应用1周后IgA浓度明显提高，IL-6明显提高，IL-10显著下降。红细胞C3b受体花结率(RRCR)明显提高。结论 肠内营养对重症胰腺炎病人免疫功能有增强作用。     

The acute effects of AICAR on purine nucleotide metabolism and postischemic cardiac function

The purine precursor AICAR (5-amino-4-imidazolecarboxamide) has been advocated as a substrate for myocardial adenine nucleotide repletion during postischemic reperfusion. The purpose of this study was to investigate the acute effects of this agent on adenine nucleotides, inosine monophosphate, and postischemic ventricular function in an isolated rat heart preparation. The hearts were perfused at constant flow, either continuously for 90 minutes or for a 30 minute period followed by 10 minutes of global normothermic (37 degrees C) ischemia. The ischemic hearts were then reperfused for 15, 30, and 60 minutes. Both groups were treated with AICAR in a concentration of 100 mumol/L throughout the perfusion protocols. In the nonischemic time control group there was no effect on the levels of adenosine nucleotides or developed pressure over 90 minutes of perfusion. In contrast, AICAR treatment increased tissue inosine monophosphate content four-fold and sevenfold at 60 and 90 minutes, respectively (p less than 0.05), but had no effect on tissue adenosine monophosphate levels. During ischemia, there was a 50% decrease in adenosine triphosphate content in the AICAR-treated hearts and a thirteen-fold increase in adenosine monophosphate levels (p less than 0.05). After 60 minutes of reperfusion, adenosine triphosphate and monophosphate levels in the AICAR-treated hearts recovered to only 52% and 59% of preischemic values, respectively. These findings were similar to those observed in the untreated ischemic hearts. In contrast, tissue inosine monophosphate content in the AICAR-treated hearts during reperfusion remained significantly elevated and was fivefold greater than the reperfusion values in the untreated group. Concurrently, AICAR failed to enhance the recovery of postischemic left ventricular developed pressure. These results suggest that inhibition of the conversion of inosine monophosphate to adenosine monophosphate limits the usefulness of the agent in evaluating the temporal relationships between postischemic adenosine triphosphate repletion and recovery of myocardial function in the acute setting.     

异丙酚对急性心肌梗死大鼠心脏功能的影响

目的 观察异丙酚对急性心肌梗死大鼠血液动力学影响的量-效关系以及心肌梗死范围和心肌超微结构的变化。方法 将急性心肌梗死模型的大鼠随机分为5组（n=8）,对照组（Ⅰ）,其余大鼠分别持续静脉输注30（Ⅱ）、45（Ⅲ）、60（Ⅳ）、75（Ⅴ）mg·kg-1·h-1异丙酚30min。测定输注异丙酚30min血药浓度,观察血液动力学、心肌梗死范围和心肌超微结构的变化。结果 血药浓度为（3.4±0.9）～（12.9±2.4）μg/ml时,平均动脉压（MAP）、心率（HR）、左室收缩压（LVSP）、左室内压力变化最大速率（±dp/dtmax）、心肌耗氧指数（MOCI）均呈剂量依赖性下降（P<0.05）,左心室舒张末压（LVEDP）无明显变化（P>0.05）,心肌梗死面积为23.7％～29.2％（P>0.05）,心肌超微结构无显著性差异。结论 在血药浓度（3.4±0.9）～（12.9±2.4）μg/ml范围内,异丙酚对血液动力学及心收缩功能呈剂量依赖性抑制,对心肌梗死范围和心肌细胞超微结构无明显影响。     

静脉输注维生素E对急性胰腺炎时肺脏脂质过氧化损害的保护作用

目的观察维生素E（VE）对急性胰腺炎（AP）时肺组织脂质过氧化的保护作用。方法采用3％牛磺胆酸钠按O1mg／kg体重注入胰管内制成AP动物模型后,经肠系膜静脉按100mg／kg体重注入VE乳剂或相同体积的生理盐水,术后6小时和24小时活杀动物检测血清淀粉酶、脂肪酸及磷脂酶A_2（PLA_2）活性;肺脏组织丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性及三磷酸腺着（ATP）含量。结果VE组动物肺脏组织炎性病理改变较AP组明显减轻;血清淀粉酶、脂肪酶及PLA_2活性均较AP组显著降低（P＜0．05）。肺脏组织MDA含量较AP组巳著降低（P＜0．05）,SOD活性及ATP含量较AP组显著升高（P＜0.05）。结论氧自由基所引发的脂质过氧化作用是急性胰腺炎时肺脏损害发病过程中的重要因素之一,应用较大剂量VE可减轻肺脏组织损害。     

丁酸钠对脂多糖诱导的急性肺损伤大鼠的肺保护研究

目的 探讨丁酸钠(sodium butyrate,SB)对脂多糖(lipopolysaccharide,LPS)诱导的急性肺损伤(acute lunginjury,ALI)大鼠是否具有肺保护作用. 方法 40只雄性SD大鼠采用随机数字表法分成4组(每组10只):C组(对照组,静脉注射生理盐水2 ml/kg)、SB组(腹腔注射SB 500 mg/kg)、LPS组(静脉注射LPS 6 mg/kg)和SB+LPS组(于注射LPS后即刻和4h分别腹腔注射SB 500 mg/kg).6h后观察肺组织病理学变化,测定肺组织湿干重比(wet/dry weight ratio,W/D)、髓过氧化物酶(myeloperoxidase,MPO)活性、丙二醛(malonaldehyde,MDA)、一氧化氮(nitric oxide,NO)含量及血清肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素(interleukin,IL)-1β、IL-8、高迁移率族蛋白B1(high mobility group box 1,HMGB-1)、IL-10含量. 结果 与LPS组比较,SB+LPS组肺组织损伤程度明显减轻,W/D下降(4.48±0.23vs4.20±0.11,P＜0.05),组织MPO活性、MDA和NO含量显著降低(0.84±0.05)vs(0.68±0.03),(5.75±0.19)vs(2.74±0.20),(41 ±4)vs(33±7) (P＜0.01),血清TNF-α、IL-1β、IL-8、HMGB-1含量降低(2350±121)vs(1150±154),(395±20)vs(203±18),(89±7)vs(50±5),(115± 12)vs(62±16) (P＜0.05),IL-10含量增加(281±25)vs(101±14)(P＜0.05). 结论 SB能够通过抑制中性粒细胞聚集和促炎症因子的产生,抑制肺部脂质过氧化和硝基化效应,从而减轻肺水肿和细胞损伤,发挥肺保护作用.     

丙泊酚对重症急性胰腺炎相关肺损伤保护作用的实验研究

目的：探讨丙泊酚对大鼠重症急性胰腺炎（SAP）相关肺损伤的保护作用及机制。方法45只雄性SD大鼠随机分为3组（n=15）：假手术组（S组）、重症胰腺炎组（SAP组）、丙泊酚组（P组）。以4％牛磺胆酸钠逆行胰胆管注射的方法制作SAP模型。丙泊酚组（P组）在制作SAP模型前30分钟经股静脉注射5mg·kg^-1,随后以10mg·kg^-1·h^-1。继续持续输注。各组均于造模12小时后取材,测定血清肿瘤坏死因子-a（TNF-ct）含量;采用RT-PCR法检测肺组织细胞间粘附分子-1（ICAM-1）mRNA的表达;同时检测肺组织丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性、湿干重比及对肺脏进行病理学评分。结果与SAP组相比,P组肺组织病理损伤程度、湿／干重比、肺组织MDA含量和SOD活性以及血清TNF—a和ICAM-1mRNA水平表达均显著降低（P〈0．05）。结论丙泊酚可减轻大鼠SAP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。     

甘草甜素对大鼠脓毒血症引起的急性肺损伤的保护作用

目的 观察甘草甜素(GL)对大鼠脓毒血症引起的急性肺损伤(ALI)的保护作用.方法 采用脂多糖(LPS)尾静脉注射诱导大鼠脓毒血症引起的AI模型.雄性SD大鼠30只,随机均分为五组:对照组(C组)、模型组(S组.静注LPS 7.5 mg/kg)、GL处理组(GL1、GL2、GL3组,分别于静注LPS 7.5 mg/kg前10 min腹腔注射GL、30、60、120 mg/kg).LPS静沣后12 h,测定各组大鼠支气管肺泡灌洗液(BALF)中自细胞总数、总蛋白的含量、肺组织髓过氧化物酶(MPO)活性和湿干重比值.并观察肺组织病理学变化.结果 与C组相比.S组BALF中白细胞计数、总蛋白含量、肺组织MPO活性和湿千重比值明显增加(P<0.05);S组肺组织切片观察见明显的炎细胞浸润、充血、水肿等.与S组相比,GL1、GL2、GL3组BALF中白细胞计数、总蛋白含量、肺组织MPO活性和肺组织湿干重比值均降低(P<0.05).病理学损伤也减轻;GL3组损伤减轻较GL1、GL2组更为明显(P<0.05).结论 GL可减轻肺泡毛细血管屏障的损伤,并随着剂量的加大损伤减轻更加明显,对脓毒血症引起的急性肺损伤具有保护作用.     

The protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats

To investigate the effects of treatment with propofol administration at different time point in acute lung injury of endotoxin-induced shock rats. METHODS: 76 male wistar rats were randomly assigned to five groups: A) control group; B) endotoxemic group, receiving intravenous lipopolysaccharide (LPS) 8 mg.kg-1; C) pretreatment group, treated identically to endotoxemic group with the additional administration of propofol (5 mg.kg-1 bolus, followed by infusion at 10 mg.kg-1.h-1) of 1 hr prior to the injection of LPS; D) simultaneously treatment group, treated identically to endotoxemic group with the additional administration of propofol simultaneously with the injection of LPS; E) post-treatment group, which was treated identically to endotoxemic group except for administration of propofol 1 hr after the injection of LPS. PaO2, pH, MAP and survival rate were recorded and plasma NO, TNF-alpha were measured during 5-hr after the injection of LPS. After the rats were killed, lung tissue was sampled to measured expression of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT), myeloperoxidase (MPO) activity, malondialdehyde (MDA), wet-to-dry lung weight ratio (W/D), and pulmonary permeability index (PPI). RESULTS: Compared with the endotoxemic group, both the pretreatment and simultaneously treatment groups, significantly improved PaO2, pH, MAP and 5th hour survival rate of rats, and attenuated endotoxin-induced increased iNOSmRNA, NT expression, MPO activity and MDA level in lung tissue, and decreased pulmonary microvascular permeability, TNF-alpha, NO in plasma. But these beneficial efficacies were blunted in the post-treatment group. CONCLUSIONS: These findings showed that propofol administration may provide protective effects on acute lung injury in endotoxin-induced shock.     

中药胰必清对急性出血坏死性胰腺炎急性肺损伤大鼠肺泡巨噬细胞的作用

目的 观察TLR4、核转录因子(NF)-κB在急性出血坏死性胰腺炎(AHNP)大鼠肺泡巨嗜细胞的表达及应用胰必清(YBQ)治疗前后的变化.方法 72只SD大鼠平均随机分为3组:A组(假手术对照组)、B组(AHNP)及C组(AHNP+YBQ),开腹胰胆管注入5%牛磺胆酸钠法建立大鼠AHNP模型,分别于术后3、6、12、24 h处死大鼠,逆转录·聚合酶链反应(RT-PCR)法、免疫荧光共聚焦法分别检测支气管灌洗液肺泡巨噬细胞中TLR4 mRNA、NF-KB表达水平的变化,肺组织病理检查行病理学评分.结果 C组肺泡巨噬细胞3、6、12、24 h TLR4 mRNA表达水平结果为0.54、0.65、0.65、0.54,NF.KB免疫荧光检测结果为49.54、68.67、74.27、59.23,与肺组织的病理学评分相一致,随时间的延长而逐渐升高,6～12 h左右达高峰,与时间明显相关,与B组比较明显降低,差异有统计学意义(P《0.05).结论 中药胰必清能通过调节肺泡巨噬细胞中TLR4的基因表达,进一步调节NF-KB的活化来改善AHNP-ALI.     

挥发性吸入麻醉药对肺的作用

挥发性吸入麻醉药对肺的作用目前尚未有定论，其中有较多争议之处。不同种类、不同吸入浓度以及不同生理条件下的吸入麻醉药对肺的作用不同，可以引起肺的损伤作用、导致肺内分流增加，也可以产生肺的缺血／再灌注损伤的保护作用，其机制尚未完全清楚。