Resuscitation from experimental heatstroke by brain cooling therapy

We have used hypothermic retrograde jugular venous flush to cool the brain previously and to provide better resuscitation than peripheral cold saline infusion during heatstroke in the rat. The current study was performed to assess the effects of brain cooling further on production of reactive nitrogen species, reactive oxygen species, tumor necrosis factor-alpha, and interleukin-10 in both serum and brain during heatstroke. Rats, under general anaesthesia, were randomized into the following groups and given: (a) 36 degrees C or (b) 4 degrees C saline infusion in the external jugular vein immediately after onset of heatstroke. They were exposed to an ambient temperature of 43 degrees C for exactly 70 min to induce heatstroke. When the 36 degrees C saline-treated rats underwent heat stress, their survival time values were found to be 21-25 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline greatly improved survival (226-268 min). Compared with the normothermic controls, the 36 degrees C saline-treated heatstroke rats displayed higher levels of brain temperature, intracranial pressure, serum and hypothalamic nitric oxide metabolite, tumor necrosis factor-alpha and dihydroxybenzoic acid as well as hypothalamic inducible nitric oxide synthase immunoreactivity. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and hypothalamic levels of local blood flow, and partial pressure of oxygen were all significantly lower during heatstroke. The cerebrovascular dysfunction, the increased levels of nitric oxide metabolites, tumor necrosis factor-alpha, and dihydroxybenzoic acid in both the serum and the hypothalamus, and the increased levels of hypothalamic inducible nitric oxide synthase immunoreactivity occurred during heatstroke were significantly suppressed by brain cooling. Although the serum and hypothalamic interleukin-10 maintained at a negligible level before stress, they were significantly elevated by brain cooling during heatstroke. These findings suggest that brain cooling may resuscitate persons who had heatstroke by decreasing overproduction of reactive nitrogen species, tumor necrosis factor-alpha, reactive oxygen species and cerebrovascular dysfunction, but increasing production of interleukin-10.     

Human umbilical cord blood-derived CD34+ cells cause attenuation of multiorgan dysfunction during experimental heatstroke

Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.     

Predictors of multi-organ dysfunction in heatstroke

Background: Heatstroke is a medical emergency that results from failure of thermoregulatory mechanism coupled with an exaggerated acute phase response, causing an elevation in core body temperature that rises above 40°C, producing multi-organ dysfunction. It carries a high mortality rate, and in survivors, a risk of permanent neurological damage.

Objective: To investigate predictors of multiple organ dysfunction syndrome in patients presenting with heatstroke.

Methods: We investigated 28 patients admitted to a hospital in southern India during the period January 1998 to December 2001. Using a standard form, we collected data on the patients' characteristics, laboratory data, and outcome, and compared those with multiple organ dysfunction with those without such dysfunction.

Results: We found that more than three quarters of the studied patients developed multiple organ dysfunction, with the most common dysfunction being respiratory failure. Among the selected predictors, metabolic acidosis 14 of 16 patients, 87.5%; p = 0.011, elevated CPK 17 of 19 patients, 89.5%; p = 0.005, and liver enzymes elevated more than twice the normal (11 of 18 patients, 61%; p = 0.02) had the highest correlation with dysfunction of two or more organs.

Conclusions: The high mortality observed in heatstroke is secondary to multi-organ dysfunction, and among the various parameters assessed, high levels of CPK (>1000 IU/l), metabolic acidosis, and elevated liver enzymes are predictive. Aggressive measures to lower the body temperature with other supportive therapy could substantially reduce the mortality.

     

Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke

The purpose of the present study was to assess the therapeutic effect of hypothermic retrograde jugular vein flush (HRJVF) on heatstroke. HRJVF was accomplished by infusion of 4 degrees C isotonic sodium chloride solution via the external jugular vein (1.7 mL/100 g of body weight over 5 min). Immediately after the onset of heatstroke, anesthetized rats were divided into 2 major groups and given the following: 36 degrees C or 4 degrees C isotonic sodium chloride solution, i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats was exposed to room temperature (24 degrees C) and used as normothermic controls. When the 36 degrees C saline-treated rats underwent heat exposure, their survival time values were found to be 23 to 28 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 degrees C saline significantly improved survival during heatstroke (208-252 min). All heat-stressed animals displayed systemic inflammation and activated coagulation, evidenced by increased tumor necrosis factor alpha, prothrombin time, activated partial thromboplastin time, and d-dimer, and decreased platelet count and protein C. Biochemical markers evidenced cellular ischemia and injury/dysfunction: plasma levels of blood urea nitrogen, creatinine, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and alkaline phosphatase; and striatal levels of glycerol, glutamate, and lactate/pyruvate; dihydroxy benzoic acid, lipid peroxidation, oxidized-form glutathione reduced-form glutathione, dopamine, and serotonin were all elevated during heatstroke. Core and brain temperatures and intracranial pressure were also increased during heatstroke. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and striatal levels of local blood flow, partial pressure of oxygen, superoxide dismutase, catalase, glutathione peroxidase, and glutathions reductase activities were all significantly lower during heatstroke. The circulatory dysfunction, systemic inflammation, hypercoagulable state, and cerebral oxidative stress, ischemia, and damage during heatstroke were all significantly suppressed by HRJVF. These findings demonstrate that brain cooling caused by HRJVF therapy may resuscitate persons who had a stroke by attenuating cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia/injury during heatstroke.     

Progressive exercise preconditioning protects against circulatory shock during experimental heatstroke

Heat shock protein (HSP) 72 expression protects against arterial hypotension in rat heatstroke. HSP72 can also be induced in multiple organs, including hearts from rats with endurance exercise. We validated the hypothesis that progressive exercise preconditioning may confer cardiovascular protection during heatstroke by inducing the overexpression of HSP72 in multiple organs. To deal with the matter, we assessed the effects of heatstroke on mean arterial pressure, heart rate, cardiac output, stroke volume, total peripheral vascular resistance, colonic temperature, blood gases, and serum or tissue levels of tumor necrosis factor-alpha (TNF-alpha) in urethane-anesthetized rats pretreated without or with progressive exercise training for 1, 2, or 3 weeks. In addition, HSP72 expression in multiple organs was determined in different groups of animals. Heatstroke was induced by exposing the rats to a high blanket temperature (43 degrees C); the moment at which mean arterial pressure decreased from the peak value was taken as the time of heatstroke onset. Previous exercise training for 3 weeks, but not 1 or 2 weeks, conferred significant protection against hyperthermia, arterial hypotension, decreased cardiac output, decreased stroke volume, decreased peripheral vascular resistance, and increased levels of serum or tissue TNF-alpha during heatstroke and correlated with overexpression of HSP72 in multiple organs, including heart, liver, and adrenal gland. However, 10 days after 3 weeks of progressive exercise training, when HSP72 expression in multiple organs returned to basal values, the beneficial effects exerted by 3 weeks of exercise training were no longer observed. These results strongly suggest that HSP72 preconditioning with progressive exercise training protects against hyperthermia, circulatory shock, and TNF-alpha overproduction during heatstroke.     

影响重症中暑患者预后因素及其死亡原因分析

目的：探讨影响重症中暑预后的因素及死亡原因,以指导治疗。方法：收集重症中暑患者４４例,将死亡病例与治疗好转病例的临床资料进行比较,并分析死亡原因。结果：死亡组与好转组比较,体温＞４０．５℃者,昏迷程度深者,合并基础疾病、休克、心律失常者,血Ｎａ＋、血细胞比容（Ｈｃｔ）几项指标均有显著性差异（Ｐ均＜０．０１）,血Ｋ＋也有差异（Ｐ＜０．０５）。死亡原因：２４小时内主要为心、脑、循环衰竭与猝死;２４小时后主要为呼吸衰竭。结论：影响重症中暑患者预后的因素主要有体温、昏迷程度、基础疾病、心律失常、休克、低血Ｎａ＋、低血Ｋ＋、血液浓缩。治疗应针对各危险因素,应早期阻断高热引起的恶性循环,及时纠正水、电解质紊乱;防止各主要脏器的衰竭;晚期则主要预防肺部感染等并发症     

Acute inflammation causes epithelial invasion and mucosal destruction in experimental shigellosis

The gram-negative pathogen Shigella flexneri causes bacillary dysentery, an invasive disease of the human colonic mucosa. A major characteristic of the infectious process is the occurrence of an acute inflammatory reaction of mucosal tissues which is generally consequence of primary invasion and destruction of colonic epithelial cells by the pathogen. Confirming in vitro demonstration that S. flexneri is unable to invade the apical pole of colonic cells and that polymorphonuclear (PMN) cells may assist them in reaching the basal side of epithelial cells where they can invade, we have provided here in vivo evidence that S. flexneri enters the epithelial barrier essentially through the dome of lymphoid follicles at the early stage of infection and that subsequent invasion and destruction of the epithelium is primarily due to immigration of leukocytes, particularly PMN that destroy cohesion of the epithelial barrier. These conclusions are based on experiments carried out in infected rabbit ligated intestinal loops, with some animals treated by an anti-CD18 monoclonal antibody that blocked immigration of leukocytes into infected tissues.     

The protective effect of hypervolemic hemodilution in experimental heatstroke

The authors tested the hypothesis in a rat model that hypervolemic hemodilution during heatstroke affected the mean arterial pressure (MAP), striatal dopamine (DA) release, and local cerebral blood flow and neuronal damage score in different brain structures. The heatstroke was induced by exposing the urethane-anesthetized rats to an ambient temperature of 42 degrees C. Hypervolemic hemodilution was produced by intravenous administration of 10% human albumin. Relative and absolute blood flow in the corpus striatum were determined using the laser Doppler flowmetry and the autoradiography diffusible tracer technique, respectively. The DA release in the striatum was estimated using the in vivo microdialysis technique. After onset of heatstroke, animals with hypervolemic state alone, produced by saline or heparinized blood injection, displayed higher values of DA release, as well as neuronal damage score in the striatum, hypothalamus, or cortex, but lower values of MAP and blood flow in the striatum, hypothalamus, or cortex compared to normothermic controls. However, the heatstroke-induced arterial hypotension, cerebral ischemia, increased striatal DA overload, and increased neuronal damage score were attenuated by induction of both hypervolemic and hemodilution state with 10% albumin either before or after the onset of heatstroke. In addition, constant infusions of a vasopressor agent phenylephrine (2 microg kg(-1) min(-1)) after the onset of heatstroke failed to maintain appropriate levels of MAP and resulted in no protection against heatstroke. Thus, it appears that the observed benefit of the 10% albumin is secondary to hemodilution and/or maintenance of MAP.     

Hypothermia attenuates circulatory shock and cerebral ischemia in experimental heatstroke

We tested the hypothesis in a rat model that body cooling suppresses circulatory shock and cerebral ischemia in heatstroke. Animals under urethane anesthesia were exposed to water blanket temperature (Tblanket) of 42 degrees C until mean arterial pressure (MAP) and local cerebral blood flow (CBF) in the hippocampus began to decrease from their peak levels, which was arbitrarily defined as the onset of heatstroke. Control rats were exposed to 26 degrees C. Extracellular concentrations of glutamate, glycerol, lactate, and lactate/pyruvate in the hippocampus were assessed by microdialysis methods. Cooling was accomplished by decreasing Tblanket from 42 degrees C to 16 degrees C. The values of MAP and CBF after the onset of heat stroke in heatstroke rats received no cooling were all significantly lower than those in control rats. However, the neuronal damage score and extracellular levels of ischemia and damage markers in the hippocampus were greater. Cooling immediately after the onset of heatstroke reduced the heatstroke-induced circulatory shock, cerebral ischemia, neuronal damage, and surge of tissue ischemia and damage markers in the hippocampus, and resulted in prolongation of survival time. Delaying the onset of cooling reduced the therapeutic efficiency. The results suggest that body cooling attenuates circulatory shock and cerebral ischemia insults in heatstroke.     

口服精氨酸对糖尿病大鼠皮肤组织糖利用的影响

目的:探讨精氨酸对糖尿病大鼠皮肤组织糖利用的影响及其可能的机制。方法:SD大鼠随机分为正常对照组、糖尿病对照组、糖尿病精氨酸治疗组和糖尿病甘氨酸对照组。糖尿病模型通过腹腔注射链脲佐菌素建立。模型成功后糖尿病精氨酸治疗组和糖尿病甘氨酸对照组分别予精氨酸和甘氨酸200mg/(kg·d)喂养,测其不同时期的血糖和体质量。8周后取胰腺组织观察组织形态学改变,并对血浆胰岛素含量、皮肤组织糖含量进行检测。结果:与甘氨酸对照组相比,精氨酸治疗后血糖恢复正常者显著增加;与糖尿病组相比,胰腺组织修复不明显的情况下,应用精氨酸后,血浆胰岛素增加,皮肤组织糖含量降低,体质量增加。结论:口服精氨酸可通过改善胰腺功能,促进胰岛素分泌,增加糖尿病皮肤组织等糖利用,降低血糖。     

Early organ dysfunction course,cooling time and outcome in classic heatstroke

Purpose  To describe the course of early organ dysfunction in a cohort of patients admitted in ICU suffering classic heatstroke. Methods  Prospective observational single-centre cohort study with a 1-year follow-up. Interventions  None. Measurements and main results  Clinical and biological data of 22 patients were analysed. Median body temperature on admission was 41.1°C. Respiratory, circulatory, haematological, hepatic and renal function all deteriorated within the first 24 h of admission. ICU-mortality was 63.6%. Cooling time, serum lactate, serum cardiac troponin I and creatinine were significantly higher in non-survivors. Early ICU-mortality (within 7 days of ICU stay) was due to multiple organ failure. Late ICU-mortality was due to neurological disability. Conclusions  Classic heat stroke may demonstrate a rapidly worsening organ dysfunction course leading to death even though cooling procedures and intensive care management are promptly started. Presented in part at the 17th Annual Congress of the European Society of Intensive Care Medicine, Berlin, 2004 (Intensive Care Med 30: S776).     

糖尿病血管病变的预防性干预策略:对内皮细胞功能不全的认识与改善

糖尿病血管病变的发生与多种因素有关,其中重要的病理变化之一就是内皮细胞功能不全,而后者又与胰岛素抵抗、血管收缩与舒张平衡失调、高脂血症、肝细胞生长因子的缺乏等相关联,故而在这些方面给予相应的治疗相信可以延缓或改善糖尿病血管病变的发生。现将该问题作一综述。     

阿尔兹海默病小鼠不同时期脑血管的功能改变及机制

目的:研究散发性阿尔兹海默病(sAD)小鼠模型早期、中期脑血管功能改变及机制。方法:通过脑室内注射链脲霉素建立sAD模型,造模2周后采用Morris水迷宫评估小鼠认知功能,验证模型成立;利用活体成像技术检测假手术组、早期组(造模1周)、中期组(造模3个月)小鼠脑皮层动脉、穿支动脉、静脉及毛细血管对短暂高碳酸血症的血管反应性,并分别使用一氧化氮合酶抑制剂L-NAME及前列腺素合成抑制剂吲哚美辛阻断其相关通路,观察各组同种血管反应性变化。结果:与假手术组相比,造模2周后sAD小鼠学习、空间记忆能力显著下降。与假手术组相比,造模1周小鼠的脑皮层动脉、毛细血管的反应性均显著下降,皮层动脉反应性于造模3个月时恢复,而毛细血管反应性无明显恢复。LNAME可显著增加sAD小鼠脑动脉、毛细血管反应性。吲哚美辛可明显减弱sAD小鼠脑动脉反应性,但对毛细血管无影响。结论:sAD小鼠早期存在的脑血管功能损伤,可能参与认知障碍的发生和发展,其机制与一氧化氮通路改变有关。     

Zymosan-induced generalized inflammation: experimental studies into mechanisms leading to multiple organ dysfunction syndrome

Patients suffering from multiple organ dysfunction syndrome (MODS) comprise a heterogeneous population, which complicates research in its pathogenesis. Elucidation of the mechanisms involved in the development of MODS will ultimately necessitate the collection of tissue samples and the performance of invasive procedures. These requirements greatly reduce the possibilities for research in human subjects. Therefore, an animal model for MODS is a necessary and valuable tool. In the mid 1980s, the zymosan-induced generalized inflammation (ZIGI) model was introduced. Intraperitoneal injection of zymosan in mice or rats leads, in the course of 1 to 2 weeks, to increasing organ damage and dysfunction. The ZIGI model has been recognized as the one that best resembles human MODS and it has been used widely to study systemic inflammation in relation to organ failure. This review describes the ZIGI model and gives an overview of the results obtained.     

不同核心温度下劳力性热射病大鼠凝血功能障碍特征研究

目的 劳力性热射病常合并严重的凝血功能障碍,本研究旨在探讨劳力性热射病大鼠处于不同核心温度时凝血功能障碍的特征。方法 选取SPF级SD大鼠25只,并完成遥测温度胶囊腹腔植入术。术后恢复1周后,将大鼠随机分为对照组(n=5)与模型组[40℃组(n=5)、41℃组(n=5)、42℃组(n=5)及43℃组(n=5)]。采用腹腔遥测温度胶囊监测大鼠核心体温,模型组大鼠均于温度40℃、相对湿度70%的环境下跑步,建立劳力性热射病模型,核心温度达到预定温度时即认为模型建立成功,记录建模成功时的跑步时间和距离。各组劳力性热射病模型大鼠在核心温度达标时,检测凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、血小板计数、纤维蛋白原、凝血酶时间(TT)、血栓调节蛋白(TM)、凝血酶敏感蛋白-1(TSP-1)、血管性血友病因子(vWF)、纤溶酶原激活物抑制物-1(PAI-1)及血乳酸水平;对照组大鼠在模型组大鼠进行实验前采血并对上述相关指标进行检测。结果 与对照组比较,核心温度40℃组大鼠的血小板计数开始明显降低,且随核心温度升高而下降,差异有统计学意义(P<0.05)。与对照组比较,核心温度4...     

Resuscitation from experimental heatstroke by transplantation of human umbilical cord blood cells

OBJECTIVE: Human umbilical cord blood cells (HUCBCs) are effective in the treatment of conventional stroke in experimental models. In the study described herein, we administered HUCBCs into the femoral vein or directly into the cerebral ventricular system and assessed their effects on circulatory shock, cerebral ischemia, and damage during heatstroke. DESIGN: Controlled, prospective study. SETTING: Hospital medical research laboratory. SUBJECTS: Sprague-Dawley rats (287 +/- 16 g body weight, males). INTERVENTIONS: Anesthetized rats, immediately after the onset of heatstroke, were divided into four major groups and given the following: a) normal saline or AIM-V medium intravenously (0.3 mL) or intracerebroventricularly (10 microL); b) peripheral blood mononuclear cells (5 x 10 in 0.3 mL AIM-V medium, intravenously, or 5 x 10 in 10 microL AIM-V medium, intracerebroventricularly); or c) HUCBCs (5 x 10 in 0.3 mL AIM-V medium, intravenously, or 5 x 10 in 10 microL AIM-V medium, intracerebroventricularly). Another group of rats, under urethane anesthesia, were exposed to room temperature (26 degrees C) and used as normothermic controls. Urethane-anesthetized animals were exposed to an ambient temperature of 43 degrees C to induce heatstroke. Their physiologic and biochemical parameters were continuously monitored. MEASUREMENTS AND MAIN RESULTS: When the vehicle-treated rats underwent heat exposure, their survival time values were found to be 21-23 mins. Resuscitation with intravenous or intracerebroventricular doses of HUCBCs, but not peripheral blood mononuclear cells, immediately at the onset of heatstroke significantly improved survival during heatstroke (61-148 mins). As compared with values for normothermic controls, the vehicle-treated heatstroke rats had lower mean arterial pressure, cerebral blood flow, and brain PO2 values but higher intracranial pressure and cerebral ischemia values and more injury markers. The circulatory shock, intracranial hypertension, cerebral hypoperfusion and hypoxia, increment of cerebral ischemia, and damage markers during heatstroke were all significantly attenuated by intravenous or intracerebroventricular delivery of HUCBCs but not peripheral blood mononuclear cells. CONCLUSIONS: We successfully demonstrate that HUCBC therapy may resuscitate heatstroke victims by reducing circulatory shock and cerebral ischemic injury; central delivery of HUCBCs seems superior to systemic delivery of HUCBCs in resuscitating patients with heatstroke.     

乌司他丁减轻重症中暑大鼠肺的炎症和氧化损伤

目的 观察乌司他丁对重症中暑大鼠肺损伤的作用.方法 48只大鼠随机(随机数字法)分为空白组(HS)、低剂量乌司他丁组(LUTI)、高剂量乌司他丁组(HUTI)和对照组(Sham)4组,每组12只.通过人工气候舱制备重症中暑大鼠模型,监测直肠温度(Tc)、监测心率(HR)和平均动脉压(MAP),记录Tc＞42℃的时间和重症中暑发生时间,分别于热打击开始后0 min、20 min、40 min和60 min采动脉血检测血氧分压(PaO2)和二氧化碳分压(PaCO2),并于60 min留取支气管肺泡灌洗液(BALF)并用酶联免疫法检测其中的肿瘤坏死因子-α(TNF-α)、白介素-1 β(IL-1β)和白介-6(IL-6)质量浓度,收集肺组织进行病理分析和诱导性氧化亚氮(iNOS)的Western blot检测.采用PASW Statistics 17.0统计软件行方差分析,生存分析使用Kaplan-Mier曲线和Log Rank检验,以P＜0.05为差异具有统计学意义.结果 LUTI和HUTI组相比HS组在Tc＞42℃的时间(P=0.00)、重症中暑发生时间(P=0.00)和中位生存时间(P=0.00)均延长.热打击后60 min时HS组PaO2较其他三组明显降低(P=0.00),而LUTI和HUTI组之间差异无统计学意义(P=0.91).同时,HS组PaCO2较其他三组明显升高(P=0.00),LUTI和HUTI组之间差异无统计学意义(P=0.79).LUTI和HUTI组大鼠的BALF中TNF-α、IL-1β和IL-6浓度较HS组低(P=0.00,P=0.00和P=0.00),而且HUTI组的炎症介质浓度也低于LUTI组(P=0.02,P=0.04和P=0.04).病理结果显示LUTI和HUTI组大鼠肺损伤较HS组轻(p=0.00).肺组织iNOS蛋白表达比较中,HS组较LUTI和HUTI组增加(P=0.00),而LUTI组表达量也高于HUTI组(P=0.03).结论 乌司他丁具有改善重症中暑大鼠呼吸衰竭和预后的效果,这种作用可能与减轻肺组织的炎症和氧化损伤有关.