A membrane-permeable radical scavenger reduces the organ injury in hemorrhagic shock.

Reactive oxygen species (ROS) contribute to the multiple organ failure (MOF) in hemorrhagic shock. Here we investigate the effects of a membrane-permeable radical scavenger (tempol) on the circulatory failure and the organ injury and dysfunction (kidney, liver, lung, intestine) associated with hemorrhagic shock in the anesthetized rat. Hemorrhage (sufficient to lower mean arterial blood pressure to 500 mmHg for 90 min) and subsequent resuscitation with shed blood resulted (within 4 h after resuscitation) in a delayed fall in blood pressure, renal and liver injury and dysfunction as well as lung and gut injury. In all organs, hemorrhage and resuscitation resulted in the nitrosylation of proteins (determined by immunohistochemistry for nitrotyrosine) suggesting the formation of peroxynitrite and/or reactive oxygen species. Treatment of rats upon resuscitation with the membrane-permeable radical scavenger tempol (30 mg/kg bolus injection followed by an infusion of 30 mg/kg/h i.v.) attenuated the delayed circulatory failure as well as the multiple organ injury and dysfunction associated with hemorrhagic shock. Thus, we propose that an enhanced formation of ROS and/or peroxynitrite importantly contributes to the MOF in hemorrhagic shock, and that membrane-permeable radical scavengers, such as tempol, may represent a novel therapeutic approach for the therapy of hemorrhagic shock.     

缝隙连接通讯对创伤失血性休克自由基代谢和炎症因子释放的影响

目的探讨缝隙连接通讯对创伤失血性休克自由基代谢和炎症因子的影响。方法采取钳夹一侧股骨中段致其粉碎性骨折合并股动脉放血的方式制备新西兰兔创伤失血性休克模型。将制成模型的24只新西兰大白兔随机分为三组(n=8):创伤休克组(Ⅰ组),创伤休克复苏组(Ⅱ组)和创伤阻断组(Ⅲ组)。模拟救援过程,将各动物模型分为创伤期、休克期、复苏期和观察期。监测收缩压、舒张压、平均动脉压、心率、呼吸等生理指标,并记录各时点的数值。在各个时点抽取兔血,离心,取上清检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1(IL-1)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)等炎症因子(ELISA法);同时检测丙二醛(MDA)、超氧化物歧化酶(SOD)等自由基代谢指标。结果创伤失血性休克后血液回输复苏可显著减少促炎因子TNF-α、IL-1、IL-6的释放(P<0.05),显著增加抗炎因子IL-10的释放(P<0.05);缝隙连接通讯早期阻断后,可减少创伤休克期TNF-α、IL-6等部分促炎因子的产生释放而较基础值无显著变化,对IL-10等抗炎因子与Ⅱ组比较无显著影响(P>0.05)。同时,血液回输也可显著减少自由基过氧化反应指标MDA的产生释放(P<0.05),增加因创伤休克而降低的抗氧化酶SOD的产生释放(P<0.05);缝隙连接通讯早期阻断后,可减少创伤休克期MDA的产生释放而较基础值无显著变化,对抗氧化酶SOD与Ⅱ组比较无显著影响(P>0.05)。结论在创伤失血性休克早期阻断缝隙连接通讯,可减少部分促炎因子的产生释放和自由基的过氧化反应,而对抗炎因子和抗氧化酶无显著作用。     

A free radical scavenger, edaravone (MCI-186), diminishes intestinal neutrophil lipid peroxidation and bacterial translocation in a rat hemorrhagic shock model

OBJECTIVE: To investigate the effects of edaravone, a novel free radical scavenger, on bacterial translocation induced by hemorrhagic shock. DESIGN: Prospective, randomized, unblinded animal study. SETTING: Surgical research laboratories of Shiga University of Medical Science. SUBJECTS: Male specific-pathogen-free Sprague-Dawley rats. INTERVENTIONS: The rats were randomly divided into three groups: conventional saline treatment, edaravone treatment, and sham shock induction. The saline and edaravone groups were subjected to hemorrhagic shock (mean arterial pressure of 30 mm Hg, for 30 or 60 mins). Rats were killed 30 or 60 mins after shock induction. Mesenteric lymph nodes were cultured for determination of bacterial translocation. Systemic plasma silkworm larvae plasma test, which can detect peptidoglycan and beta-glucan, and endotoxin tests were performed. Immunohistochemistry for 4-hydroxy-2-nonenal (4-HNE) was used to assess lipid peroxidation after shock. MEASUREMENTS AND MAIN RESULTS: The incidence and magnitude of hemorrhagic-shock-induced bacterial translocation to mesenteric lymph nodes were reduced by edaravone. Hemorrhagic-shock-induced increase of plasma silkworm larvae plasma test was also reduced by edaravone. Immunohistochemistry for 4-HNE showed many 4-HNE-positive cells in the lamina propria of the ileum 60 mins after hemorrhagic shock. Double immunohistochemistry revealed that many of these 4-HNE-positive cells were also myeloperoxidase positive. Moreover, the percentage of double-labeled cells with 4-HNE and myeloperoxidase in myeloperoxidase-positive cells was significantly lower in the edaravone group than in the saline group. CONCLUSIONS: The present findings suggest that lipid peroxidation of intestinal neutrophils is involved in bacterial translocation during hemorrhagic shock and that edaravone is potentially useful in diminishing bacterial translocation after hemorrhagic shock.     

一氧化碳中毒时小鼠脑内自由基及其清除系统的变化

目的 观察小鼠脑内自由基及自由基清除系统在一氧化碳(CO)中毒和高压氧治疗后的变化，L-硝基精氨酸甲酯(L-NAME)在CO中毒血-脑脊液屏障损伤中的作用，探讨这些变化与CO致脑损伤的关系。方法 分光光度计法分别测定各组小鼠脑内NO、NOS、MDA、SOD、GSH-Px、CAT以及L-NAME干预治疗的小鼠脑组织内伊文思蓝的含量。结果①中毒后NO含量和NOS活性降低，HBO使NOS活性明显恢复，有一定的NO恢复作用。②CO中毒后，MDA明显增多，SOD活性下降，HBO治疗抑制了MDA的增多，有助于SOD活性恢复；③GSH-Px和CAT活性在CO中毒后增强，HBO使GSH-Px活性进一步增强，而CAT活性回到基线；④CO使小鼠血-脑脊液屏障通透性增高，L-NAME可减轻其损伤。结论 CO中毒后脑内氧自由基生成明显增多，HBO有助于减轻其损伤。三种抗氧化酶在CO中毒时出现的变化有利于清除自由基，而HBO推动了这一作用。CO中毒后早期应用NOS抑制剂可减轻对血-脑脊液屏障的损害，对急性CO中毒所致脑水肿有防治作用。     

延迟液体复苏对失血性休克大鼠炎性反应的影响

目的:探讨延迟液体复苏对失血性休克大鼠炎性反应的影响。方法:将40只大鼠随机分为休克后即刻复苏组、休克后延迟30 min复苏组、休克后延迟60 min复苏组、未复苏组。采用Wiggers方法制备可控性失血性休克模型。记录复苏开始即刻(0 min),30、90、150、210、270、330 min平均动脉压水平,并采血测定IL-6、TNF-α和IL-10浓度。结果:液体复苏组复苏开始后各时点平均动脉压水平无明显差异。与未复苏组相比,休克后延迟30、60 min复苏组IL-6、TNF-α浓度明显增加,休克后延迟60 min复苏组IL-10浓度显著降低(P<0.01)。结论:在控制性失血性休克动物模型,延迟液体复苏可使促炎细胞因子生成增加,其增加的程度与延迟复苏时间密切相关。     

Edaravone,a novel free radical scavenger,prevents liver injury and mortality in rats administered endotoxin

We postulated that a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone; EDA), would attenuate inflammatory cytokine and chemokine expression in the liver after lipopolysaccharide (LPS) challenge through its antioxidant effect. Rats were administered EDA (0.3, 1.5, 3.0, 6.0, and 12.0 mg/kg) or the same volume of saline intravenously just after LPS (10 mg/kg) injection and then was continued intermittently every 2 h (five administrations in total). Survival was assessed for the next 24 h. In separate experiments, rats were sacrificed at 60 min, 90 min, 6 h, and 9 h after LPS injection. Serum and liver sections were collected for further analysis. Survival was improved by EDA in a dose-dependent manner up to 3 mg/kg, and maximum effects were observed at a dose of 3 mg/kg. After LPS injection, alanine aminotransferase levels increased significantly to about 1,250 IU/l in the vehicle-treated group, whereas values were blunted by about 80% by EDA. Furthermore, increases in 4-hydroxynonenal-modified proteins were also blunted in the liver by EDA. Moreover, mRNA expressions of macrophage infiltrating protein-2, monocyte chemoattractant protein (MCP)-1 and MCP-5 were attenuated by EDA. As a result, increases in the number of infiltrating inflammatory cells and mRNA expression of inflammatory cytokines such as tumor necrosis factor-alpha and interleukin-6 were significantly blunted in the liver by EDA. This reduction was accompanied by a significant reduction of their serum levels. In conclusion, EDA prevented liver injury by both inhibition of recruitments of inflammatory cells and expression of inflammatory cytokine levels in the liver.     

Dihydralazine treatment limits liver injury after hemorrhagic shock in rats

OBJECTIVE: Impaired hepatic perfusion after hemorrhagic shock frequently results in hepatocellular dysfunction associated with increased mortality. This study characterizes the effect of the vasodilators dihydralazine and urapidil on hepatocellular perfusion and integrity after hemorrhagic shock and resuscitation. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University experimental laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: To register systemic and regional hepatic hemodynamics, rats (n=6 per group) were instrumented and randomly assigned to the following groups: shock+vehicle; shock+dihydralazine (1.5 mg/kg); or shock+urapidil (3 mg/kg). After 1 hr of hemorrhagic shock, animals were resuscitated for 5 hrs and mean arterial pressure was maintained at 70+/-5 mm Hg by administration of dihydralazine or urapidil. To evaluate hepatic heme oxygenase-1 expression and liver injury (determination of levels of alanine and aspartate aminotransferase [ALT, AST] and histology), an additional series of experiments with six animals per group was performed. At the end of each experiment, animals were killed and blood and liver tissue was obtained for subsequent analyses. MEASUREMENTS AND MAIN RESULTS: Dihydralazine increased cardiac output and portal and hepatic microvascular flow (p<.05) and reduced liver injury after shock (lower ALT and AST levels [p<.05]; improvement of histopathological changes). In contrast, urapidil had no effect on portal flow or liver injury. Hepatic heme oxygenase-1 mRNA expression was upregulated in animals subjected to hemorrhagic shock but did not differ among experimental groups. CONCLUSIONS: Dihydralazine increases nutritive portal and hepatic microvascular flow and limits liver injury after hemorrhagic shock. This protective effect appears to be the result of increased cardiac output and increased portal flow. These findings may offer a new strategy for hepatic protection after hemorrhagic shock.     

Esophageal capnometry during hemorrhagic shock and after resuscitation in rats

Background  

Splanchnic perfusion following hypovolemic shock is an important marker of adequate resuscitation. We tested whether the gap between esophageal partial carbon dioxide tension (PeCO ₂) and arterial partial carbon dioxide tension (PaCO ₂) is increased during graded hemorrhagic hypotension and reversed after blood reinfusion, using a fiberoptic carbon dioxide sensor.     

Mannitol in cardioplegia as an oxygen free radical scavenger measured by malondialdehyde

Oxygen free radicals (OFRs) are associated with ischaemia-reperfusion injury involving many organs, including the heart, which can lead to depressed cardiac function and abnormalities in the cardiac ultrastructure. This is seen upon the release of the aortic crossclamp when the ischaemic myocardium is reperfused in patients undergoing cardiopulmonary bypass (CPB). Various studies have shown that by adding OFR scavenging agents or antioxidants to the CPB prime or cardioplegia, cardiac performance improves. Mannitol is an osmotic diuretic with free radical scavenging properties, which has been shown to reduce the extent of ischaemic injury and improve the function of the myocardium. This study evaluated how effective mannitol is as an OFR scavenger by administering different concentrations of cardioplegia antegrade into the aortic root, thus maximising its effects directly upon the myocardium rather than being diluted in the CPB prime. Thirty-three patients undergoing primary coronary artery bypass grafting (CABG) were, by double blind random selection, allocated into one of three groups: group 1, a control group (consisting of 11 patients) receiving no mannitol; group 2 (11 patients), receiving a concentration of 4 g/l; and group 3 (11 patients), receiving 8 g/l. Three blood samples were taken directly from the coronary sinus during bypass: the first sample at the start of bypass, just prior to the crossclamp being applied; the second sample just after removal of the crossclamp; and the third sample just prior to termination of bypass. All samples were then centrifuged and the plasma analysed for malondialdehyde (MDA) using high-performance liquid chromatography (HPLC). MDA, an endproduct of lipid peroxidation, causes cellular damage and disruption of cell membranes when tissue antioxidants are exhausted. The more MDA produced, the greater the depletion of tissue antioxidants secondary to OR formation during reperfusion when the aortic crossclamp is removed. HPLC is a useful biochemical study; however, it is not a direct indicator of depressed myocardial function, such as an invasive test would be, and this should be borne in mind. Statistically, the results do not show a significant difference among the three groups or among the three samples. However, a trend can be seen, which shows lower levels of MDA in the two groups receiving mannitol and there is an indication of a rise in MDA levels upon the start of reperfusion in the two groups receiving mannitol, but not the control group. It is concluded that further samples would be needed to find a significant difference in MDA concentrations.     

Effects of mild hypothermia on survival and serum cytokines in uncontrolled hemorrhagic shock in rats

Previous studies have suggested benefit of mild hypothermia during hemorrhagic shock (HS). This finding needs additional confirmation and investigation into possible mechanisms. Proinflammatory cytokines are mediators of multiple organ failure following traumatic hemorrhagic shock and resuscitation. We hypothesized that mild hypothermia would improve survival from HS and may affect the pro- and anti-inflammatory cytokine response in a rat model of uncontrolled HS. Under light halothane anesthesia, uncontrolled HS was induced by blood withdrawal of 3 mL/100 g over 15 min followed by tail amputation. Hypotensive (limited) fluid resuscitation (to prevent mean arterial pressure [MAP] from decreasing below 40 mmHg) with blood was started at 30 min and continued to 90 min. After hemostasis and resuscitation with initially shed blood and Ringer's solution, the rats were observed for 72 h. The animals were randomized into two HS groups (n = 10 each): normothermia (38 degrees C +/- 0.5 degrees C) and mild hypothermia (34 degrees C +/- 0.5 degrees C) from HS 30 min until resuscitation time (RT) 60 min; and a sham group (n = 3). Venous blood samples were taken at baseline, RT 60 min, and days 1, 2, and 3. Serum interleukin (IL)-1beta, IL-6, IL-10, and tumor necrosis factor (TNF)-alpha concentrations were quantified by ELISA. Values are expressed as median and interquartile range. Survival time by life table analysis was greater in the hypothermia group (P = 0.04). Survival rates to 72 h were 1 of 10 vs. 6 of 10 in the normothermia vs. hypothermia groups, respectively (P = 0.057). All cytokine concentrations were significantly increased from baseline at RT 60 min in both HS groups, but not in the shams. At RT 60 min, in the normothermia vs. hypothermia groups, respectively, IL-1beta levels were 185 (119-252) vs. 96 (57-135) pg/mL (P = 0.15); IL-6 levels were 2242 (1903-3777) vs. 1746 (585-2480) pg/mL (P = 0.20); TNF-alpha levels were 97 (81-156) vs. 394 (280-406) pg/mL (P= 0.02); and IL-10 levels were 1.7 (0-13.3) vs. 15.8 (1.9-23.0) pg/mL (P = 0.09). IL-10 remained increased until day 3 in the hypothermia group. High IL-1beta levels (>100 pg/mL) at RT 60 min were associated with death before 72 h (odds ratio 66, C.I. 3.5-1255). We conclude that mild hypothermia improves survival time after uncontrolled HS. Uncontrolled HS induces a robust proinflammatory cytokine response. The unexpected increase in TNF-alpha with hypothermia deserves further investigation.     

高压氧对失血性休克复苏后炎症反应的影响

目的观察高压氧对大白鼠失血性休克复苏后炎症反应的影响并探讨其作用机制。方法Wistar大鼠随机分为三组：高压氧治疗组、休克组和对照组。建立大鼠失血性休克模型,自体血和生理盐水复苏后应用2．0绝对大气压高压氧治疗,于休克前、休克后、复苏后和复苏后24h取血检测血红细胞SOD、血浆卧限a、血浆iNOS值,并进行统计学（one-way ANOVA plus SNK）分析。观察复苏后24h大鼠肝、肠、肺组织病理改变并进行病理损伤评分。结果复苏后24h高压氧治疗组血红细胞SOD值高于休克组,高压氧治疗组血浆iNOS值和TNFoa值低于休克组,差异具有统计学意义（P〈0．05）。病理损伤评分：高压氧治疗组病理损伤与休克组相比减轻,差异具有统计学意义（P〈0．05）。结论 高压氧可能通过增强机体清除活性氧和自由基、阻止炎症介质的产生,进而减轻大鼠失血性休克复苏后的炎症反应和组织脏器的病理损伤。     

Irreversible hemorrhagic shock in germfree rats

Evidence has been provided that a state of irreversible hemorrhagic shock can be induced in a bacteria-free environment in rats reared under germfree conditions. The response to bleeding, the duration of the hypotensive episode and the pathological changes were the same in the germfree and in normal stock rats. The findings are interpreted as evidence opposed to the concept that bacteria or bacterial products are implicated, as primary factors, in the pathogenicity of shock.     

Peritoneal ventilation with oxygen improves outcome after hemorrhagic shock in rats

OBJECTIVE: In experimental pulmonary consolidation with hypoxemia in rabbits, peritoneal ventilation (PV) with 100% oxygen (PV-O2) improved PaO2. We hypothesized that PV-O2 could improve outcome after hemorrhagic shock (HS) with normal lungs, by mitigating dysoxia of the abdominal viscera. DESIGN: Randomized, controlled, laboratory animal study. SETTING: University animal research facility. SUBJECTIVE: Male Sprague-Dawley rats. INTERVENTIONS: Thirty rats under light anesthesia (N2O/oxygen plus halothane) and spontaneous breathing underwent blood withdrawal of 3 mL/100 g over 15 mins. After volume-controlled HS phase 1 of 60 mins, resuscitation phase 2 of 60 mins included infusion of shed blood and, if necessary, additional lactated Ringer's solution intravenously to control normotension from 60 to 120 mins. This was followed by observation phase 3 for 7 days. We randomized three groups of ten rats each: group I received PV-O2, starting at 15 mins of HS at a rate of 40 inflations/min, and a peritoneal "tidal volume" of 6 mL, until the end of phase 2. Group II received the same PV with room air (PV-Air). Control group III was treated without PV. MEASUREMENTS AND MAIN RESULTS: During the second half of HS phase 1, mean arterial pressures were higher in the PV-O2 group I compared with the PV-Air group II and control group III (p < .05). All 30 rats survived the 120 mins of phases 1 and 2. Survival to 7 days was achieved by ten of ten rats in PV-O2 group I; by nine of ten in PV-Air group II; and by five of ten in control group III (p < .05 vs. group I; NS vs. group II). Survival times of <7 days were 5 days in the one death of group II and ranged between 6 hrs and 4 days in the five deaths of group III. In 7-day survivors, neurologic deficit scores (0% to 10% = normal, 100% = death) were normal, ranging between zero and 8%. Necropsies of rats that died during phase 3 showed multiple areas of necrosis of the gut, some with perforations. Necropsies in the five survivors to 7 days of group III showed marked macroscopic and microscopic changes (scattered areas of necrosis of stomach and intestine, adhesions, and pale areas in the liver). These changes were absent or less severe in the nine survivors of group II. Viscera appeared normal in all ten rats of PV-O2 group I. CONCLUSIONS: Peritoneal ventilation with oxygen during and after severe hemorrhagic shock in rats seems to decrease morbidity and mortality by helping preserve viability of abdominal viscera.     

Quantification of superoxide radical production in 4 vital organs of rats subjected to hemorrhagic shock

Objective

The aim of this study was to measure the production of superoxide radical (O₂⁻), a direct indicator of oxidative stress, in 4 vital organs of rats subjected to hemorrhagic shock. For this purpose, and for the first time, a new quantitative assay for the ex vivo measurement of O₂⁻ via an established 1:1 molar relationship between O₂⁻ and 2-OH-ethidium was used. The production of lipid hydroperoxides (LOOHs), a standard method of evaluation of oxidative stress, was also used for reasons of comparison.

Methods

Sixteen male Wistar rats were divided into 2 groups: sham and hemorrhagic shock, targeting to a mean arterial pressure of 30 to 40 mm Hg for 60 minutes. Three hours after resuscitation, tissues were collected for measurement of LOOHs and O₂⁻ production.

Results

Hemorrhagic shock induced increased production of LOOHs in the gut, liver, and lungs (P < .001), whereas the production of O₂⁻ was also increased in the gut (P < .001), liver (P < .001), and, to a lesser extent, in the lungs (P < .05). The oxidative load of the kidneys, as estimated by both techniques, remained unaffected.

Conclusion

The results of this new O₂⁻ assay were comparable with the results of the established LOOHs method, and this assay proved to be accurate and sensitive in the detection and quantification of O₂⁻ production in all organs tested. Thus, the proposed direct measurement of O₂⁻ in critically ill patients often facing in extremis situations could be used as a prognostic tool and as a method to evaluate therapeutic interventions in the setting of emergency medicine.     

Prevention of granulocyte-mediated oxidant lung injury in rats by a hydroxyl radical scavenger, dimethylthiourea

Toxic, partially reduced metabolites of oxygen (toxic oxygen radicals) are increasingly implicated in acute leukocyte-mediated tissue injury. To further probe the roles of oxygen radicals in acute lung edema, I studied the effects of a recently described and very potent oxygen radical scavenger, dimethylthiourea (DMTU) (Fox, R. B., R. N. Harada, R. M. Tate, and J. E. Repine, 1983, J. Appl. Physiol., 55:1456-1459) on polymorphonuclear leukocyte (PMN) oxidant function and on two types of lung injury mediated by oxygen radicals and PMN. DMTU (10 mM) blocked 79% of hydroxyl radical (OH) production by PMN in vitro without interfering with other PMN functions, such as O-2 production, myeloperoxidase activity, chemotaxis, degranulation, or aggregation. When isolated rat lung preparations were perfused with PMN activated to produce OH, lung weights were increased from 2.3 +/- 0.2 to 11.2 +/- 0.8 g. DMTU (10 mM) prevented 70% of these increases (lung weights, 5.0 +/- 1.1 g, P less than 0.005). Finally, when intact rats were exposed to 100% O2 for 66 h, lung weight:body weight ratios were increased from 5.78 +/- 0.33 to 8.87 +/- 0.16 g. DMTU (500 mg/kg) prevented 83% of this hyperoxia-induced lung edema in vivo (lung:body weight ratios, 6.05 +/- 0.21, P less than 0.001). Pharmacokinetic studies showed that DMTU diffused effectively into lung interstitial fluids and had a relatively long half-life (25-35 h) in the circulation. Because a variety of oxygen radicals, such as superoxide (O-2), hydrogen peroxide (H2O2), or OH are produced by PMN, there is usually some uncertainty about which one is responsible for injury. However, in these studies, DMTU did not scavenge O-2 and scavenged H2O2 only very slowly while scavenging OH very effectively. Therefore, DMTU may be useful in the investigation of the roles of oxygen radicals, especially OH, in acute granulocyte-mediated tissue injury.     

大鼠休克复苏后肠黏膜屏障特点的探讨

目的 探讨失血性休克肠缺血．再灌注损伤后黏膜屏障的形态学、功能与重建的特点。方法 制作大鼠失血性休克模型，于复苏后0、1、3、6、12、24h时间段活杀并进行光镜和电镜下肠黏膜组织形态学观察、内毒素含量及尿液乳果糖，甘露醇比值的测定。结果 肠黏膜主要表现为凋亡和坏死两种损伤形式，大部分肠黏膜于6h重建，12h结构基本恢复正常，肠杯状细胞数在各组呈下降趋势；内毒素和乳果糖，甘露醇比值在6h达高峰。结论 失血性休克后肠黏膜屏障早期受累，但同时具有快速重建能力；屏障功能的恢复滞后于形态学重建。     

自由基清除剂对败血症白鼠细胞因子水平的影响

目的 研究自由基清除荆(维生素C)对败血症白鼠血清中细胞因子水平的影响，探讨败血症的早期干预治疗。方法 选取2周龄SD白鼠80只，随机分为3组，第一组为基础对照组，另两组(实验组)在采用回盲部结扎并穿刺造成败血症模型后，分别给予生理盐水及维生素C，2h后取血清测定，并观察3组间细胞因子水平的差别。结果 自由基清除剂(维生素C)组：TNF(肿瘤坏死因子)及白细胞介素-l、6、10(IL-l、IL-6、IL-10)较生理盐水组有明显下降。结论 氧自由基在败血症发生、发展过程中起重要作用，早期给予干预治疗可显著降低白鼠促炎性细胞因子水平。     

Mild hypothermia during hemorrhagic shock in rats improves survival without significant effects on inflammatory responses

OBJECTIVE: To explore the hypothesis that the survival benefit of mild, therapeutic hypothermia during hemorrhagic shock is associated with inhibition of lipid peroxidation and the acute inflammatory response. DESIGN: Prospective and randomized. SETTING: Animal research facility. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats underwent pressure-controlled (mean arterial pressure 40 mm Hg) hemorrhagic shock for 90 mins. They were randomized to normothermia (38.0 +/- 0.5 degrees C) or mild hypothermia (33-34 degrees C from hemorrhagic shock 20 mins to resuscitation time 12 hrs). Rats were killed at resuscitation time 3 or 24 hrs. MEASUREMENTS AND MAIN RESULTS: All seven rats in the hypothermia group and seven of 15 rats in the normothermia group survived to 24 hrs (p <.05). Hypothermic rats had lower serum potassium and higher blood glucose concentrations at 90 mins of hemorrhagic shock (p <.05). At resuscitation time 24 hrs, the hypothermia group had less liver injury (based on serum concentrations of ornithine carbamolytransferase and liver histology) and higher blood glucose than the normothermia group (p <.05). There were no differences in serum free 8-isoprostane (a marker of lipid peroxidation by free radicals) between the two groups at either baseline or resuscitation time 1 hr. Serum concentrations of interleukin- 1 beta, interleukin-6, and tumor necrosis factor-alpha peaked at resuscitation time 1 hr. Tumor necrosis factor-alpha concentrations were higher (p <.05) at resuscitation time 1 hr in the hypothermia group compared with the normothermic group. Serum cytokine concentrations were not different between survivors and nonsurvivors in the normothermia group. Serum cytokine concentrations returned to baseline values in both groups by 24 hrs. There were no differences in the number of neutrophils in the lungs or the small intestine between the groups. More neutrophils were found in the lungs at resuscitation time 3 hrs than at resuscitation time 24 hrs in both groups (p <.01). CONCLUSIONS: These data suggest that lipid peroxidation and systemic inflammatory responses to hemorrhagic shock are minimally influenced by mild hypothermia, although liver injury is mitigated and survival improved. Other mechanisms of benefit from mild hypothermia need to be explored.     

控制性低温对兔创伤失血性休克早期肺炎症反应的影响

目的探讨控制性低温对兔创伤失血性休克后早期肺部炎症反应和对肺组织损伤程度的影响。方法24只健康新西兰大白兔,随机分为正常对照组(C组)、常温组(N组)、浅低温组(MIH组)、中低温组(MOH组),每组6只。采用ELISA法测定肺组织匀浆上清液TNF-α、IL-6、IL-8、IL-10含量及肺水含量。结果创伤失血性休克后8h,肺组织匀浆TNF-α、IL-6、IL-8、IL-10含量均显著升高;MIH组和MOH组TNF-α含量低于N组(P<0.05),但组间差异无统计学意义;MIH组和MOH组肺组织IL-6含量显著低于N组(P<0.01);MIH组肺组织IL-8含量显著低于N组和MOH组(P<0.01),MOH组肺组织IL-8含量低于N组,但差异无统计学意义;MIH组和MOH组肺组织IL-10含量均显著低于N组。创伤失血性休克后早期总肺水含量显著升高,MIH组和MOH组总肺水含量低于N组(P<0.01)。结论不同程度的控制性低温对创伤失血性休克后早期肺促炎反应和抗炎反应均有抑制作用,对创伤失血性休克后的肺组织也有一定的保护作用。浅低温对创伤后肺组织炎症反应和抗炎反应的抑制作用强于中低温,而且其可控性强,副作用相对较少,因此,浅低温更有益于创伤失血性休克后早期肺组织的保护。