Anti-inflammatory effects of anethole in lipopolysaccharide-induced acute lung injury in mice

Aims

Anethole, the major component of the essential oil of star anise, has been reported to have antioxidant, antibacterial, antifungal, anti-inflammatory, and anesthetic properties. In this study, we investigated the anti-inflammatory effects of anethole in a mouse model of acute lung injury induced by lipopolysaccharide (LPS).

Main methods

BALB/C mice were intraperitoneally administered anethole (62.5, 125, 250, or 500 mg/kg) 1 h before intratracheal treatment with LPS (1.5 mg/kg) and sacrificed after 4 h. The anti-inflammatory effects of anethole were assessed by measuring total protein and cell levels and inflammatory mediator production and by histological evaluation and Western blot analysis.

Key findings

LPS significantly increased total protein levels; numbers of total cells, including macrophages and neutrophils; and the production of inflammatory mediators such as matrix metalloproteinase 9 (MMP-9), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) in bronchoalveolar lavage fluid. Anethole (250 mg/kg) decreased total protein concentrations; numbers of inflammatory cells, including neutrophils and macrophages; and the inflammatory mediators MMP-9, TNF-α and NO. In addition, pretreatment with anethole decreased LPS-induced histopathological changes. The anti-inflammatory mechanism of anethole in LPS-induced acute lung injury was assessed by investigating the effects of anethole on NF-κB activation. Anethole suppressed the activation of NF-κB by blocking IκB-α degradation.

Significance

These results, showing that anethole prevents LPS-induced acute lung inflammation in mice, suggest that anethole may be therapeutically effective in inflammatory conditions in humans.     

Beneficial effects of ApoA-I on LPS-induced acute lung injury and endotoxemia in mice

High density lipoprotein (HDL) binds lipopolysaccharide (LPS) and neutralizes its toxicity. The aim of our study was to investigate the effects of Apolipoprotein (ApoA-I), the major apolipoprotein of HDL, on LPS-induced acute lung injury (ALI) and endotoxemia. BALB/c mice were challenged with LPS, followed by ApoA-I or saline administration for 24h. The mice were then sacrificed and histopathological analysis of the lung was performed. We found that ApoA-I could attenuate LPS-induced acute lung injury and inflammation. To investigate the mechanisms, we measured tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) levels in the serum and bronchoalveolar lavage (BAL) fluid and found that ApoA-I could significantly inhibit LPS-induced increases in the IL-1beta and TNF-alpha levels in serum (P<0.05, respectively), as well as in the IL-1beta, TNF-alpha, and IL-6 levels in BAL fluid (P<0.01 and P<0.05, P<0.05, respectively). Moreover, we evaluated the effect of ApoA-I on the mortality of L-929 cells which were attacked by LPS-activated peritoneal macrophages. We found that ApoA-I could significantly inhibit the LPS-induced cell death in a dose-dependent fashion. Furthermore, we investigated in vivo the effects of ApoA-I on the mortality rate and survival time after LPS administration and found that ApoA-I significantly decreased the mortality (P<0.05) and increased the survival time (P<0.05). In summary, the results suggest that ApoA-I could effectively protect against LPS-induced endotoxemia and acute lung damage. The mechanism might be related to inhibition of inflammatory cytokine release from macrophages.     

脂多糖和石墨粉诱导小鼠急性肺损伤病理形态学比较

目的通过比较脂多糖（LPS）和石墨粉颗粒分别诱导小鼠急性肺损伤的病理形态学差异,探讨不同来源细颗粒物成分导致急性肺损伤的可能机制。方法将140只SPF级18~20 g雄性KM小鼠随机分为7组,除正常对照组外其他组经气管内分别滴注LPS溶液及石墨粉混悬液制备急性肺损伤小鼠。记录各组动物死亡率,光镜和透射电镜下观察各组小鼠不同时间点肺组织病理变化。Western Blot检测肺组织中NE的蛋白表达,实时定量PCR法检测肺组织中MCP-1的mRNA表达。结果与正常对照组相比,G（石墨粉）组和L（LPS）组均有不同程度病理学改变,G组小鼠肺部有大量巨噬细胞渗出,L组小鼠肺部渗出物以中性粒细胞为主;肺组织中NE蛋白表达均高于正常对照组（P〈0.05）,且L组与G组之间差异有显著性（P〈0.05）;肺组织中MCP-1mRNA表达均高于正常对照组（P〈0.01）,且L组与G组之间也有显著差异（P〈0.01）。结论不同来源颗粒物引起肺部的病理损伤不同,可能引起炎症反应的机制也存在差异,即成分复杂的细颗粒物导致急性肺损伤的机制可能存在混合性。     

褪黑素对内毒素致大鼠急性肺损伤的保护作用

目的:研究内毒素(LPS)致大鼠急性肺损伤(ALI)时,p-p38蛋白激酶(p-p38MAPK)在肺组织的表达及褪黑素(MT)对肺组织的保护作用及其机制。方法:将72只健康雄性SD大鼠随机分为3组,每组24只,对照组(Control)、模型组(LPS)和褪黑素干预组(LPS+MT),采用气管内滴注LPS的方法建立大鼠ALI的模型,通过免疫组织化学染色和Western blot技术检测大鼠肺组织中p-p38蛋白激酶的表达变化,并在光镜下观察大鼠肺组织形态学变化。结果:Control组气道和肺组织可见反应极弱的p-p38蛋白激酶阳性细胞,散在分布于气道上皮细胞和肺泡上皮细胞;LPS组p-p38蛋白激酶阳性细胞较对照组明显增多(P0.05或P0.01),主要分布于浸润的炎症细胞、气道上皮细胞、肺泡上皮细胞和血管内皮细胞;LPS+MT组气道和肺组织中阳性细胞数较LPS组明显减少(P0.05或P0.01),Western blot结果与免疫组织化学一致。结论:LPS致大鼠急性肺损伤模型中,肺内炎性、非炎性细胞均有p38MAPK信号通路的激活;MT对急性肺损伤的保护机制可能与其抑制p38 MAPK信号通路的过度激活有关。     

Protective effects of intratracheally administered quercetin on lipopolysaccharide-induced acute lung injury

Background

Acute respiratory distress syndrome (ARDS) can result in a life-threatening form of respiratory failure, and established, effective pharmacotherapies are therefore urgently required. Quercetin is one of the most common flavonoids found in fruits and vegetables, and has potent anti-inflammatory and anti-oxidant activities. Quercetin has been demonstrated to exhibit cytoprotective effects through the induction of heme oxygenase (HO)-1. Here, we investigated whether the intratracheal administration of quercetin could suppress lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice as well as the involvement of HO-1 in quercetin’s suppressive effects.

Methods

Mouse model of ALI were established by challenging intratracheally LPS. The wet lung-to-body weight ratio, matrix metalloproteinase (MMP)-9 activities, and pro-inflammatory cytokine productions, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in bronchoalveolar lavage fluid (BALF) were examined in ALI mice with or without quercetin pretreatment. We also examined the effects of quercetin on LPS stimulation in the mouse alveolar macrophage cell line, AMJ2-C11 cells.

Results

Intratracheal administration of quercetin decreased the wet lung-to-body weight ratio. Moreover, quercetin decreased MMP-9 activity and the production of pro-inflammatory cytokines in BALF cells activated by LPS in advance. We determined the expression of quercetin-induced HO-1 in mouse lung, e.g., alveolar macrophages (AMs), alveolar and bronchial epithelial cells. When AMJ2-C11 cells were cultured with quercetin, a marked suppression of LPS-induced pro-inflammatory cytokine production was observed. The cytoprotective effects were attenuated by the addition of the HO-1 inhibitor SnPP. These results indicated that quercetin suppressed LPS-induced lung inflammation, and that an HO-1-dependent pathway mediated these cytoprotective effects.

Conclusions

Our findings indicated that quercetin suppressed LPS-induced lung inflammation, and that an HO-1-dependent pathway mediated these cytoprotective effects. Intratracheal administration of quercetin will lead to new supportive strategies for cytoprotection in these serious lung conditions.     

间充质干细胞移植治疗急性肺损伤的研究进展

急性肺损伤是一种临床常见的危重病症,临床上传统的治疗方法一般以尽早去除诱因、控制感染、机械通气及器官功能支持治疗为主。间充质干细胞属于成体干细胞的一种,能主动归巢至肺损伤部位,并通过向肺泡和支气管上皮细胞分化参与组织修复,同时间充质干细胞能够调节急性肺损伤时局部和全身炎症反应和免疫紊乱,从而发挥治疗作用,可能是治疗急性肺损伤的一个很有前景的方法。作者就间充质干细胞移植治疗急性肺损伤的研究进展进行综述。     

mTOR and autophagy in regulation of acute lung injury: a review and perspective

The mammalian target of rapamycin (mTOR) is a central regulator of many major cellular processes including protein and lipid synthesis and autophagy, and is also implicated in an increasing number of pathological conditions. Emerging evidence suggests that both mTOR and autophagy are critically involved in the pathogenesis of pulmonary diseases including acute lung injury (ALI). However, the detailed mechanisms of these pathways in disease pathogenesis require further investigations. In certain cases within the same disease, the functions of mTOR and autophagy may vary from different cell types and pathogens. Here we review recent advances about the basic machinery of mTOR and autophagy, and their roles in ALI. We further discuss and propose the likelihood of cell type- and pathogen-dependent functions of these pathways in ALI pathogenesis.     

Silencing of Paralemmin-3 Protects Mice from lipopolysaccharide-induced acute lung injury

Excessive inflammatory response induced by lipopolysaccharide (LPS) plays a critical role in the development of acute lung injury (ALI). Paralemmin-3 (PALM3) is a novel protein that can modulate LPS-stimulated inflammatory responses in alveolar epithelial A549 cells. However, it remains unclear whether it is involved in the progression of ALI in vivo. Therefore, we studied the role of PALM3 in the pathogenesis of ALI induced by LPS. ALI was induced by LPS peritoneal injection in C57BL/6J mice. Lentivirus-mediated small interfering RNA (siRNA) targeting the mouse PALM3 gene and a negative control siRNA were intranasally administered to the mice. We found that the expression of PALM3 was up-regulated in the lung tissues obtained from the mouse model of LPS-induced ALI. The LPS-evoked inflammatory response (neutrophils and the concentrations of proinflammatory cytokines [IL-6, IL-1β, TNF-α, MIP-2] in the bronchoalveolar lavage fluid [BALF]), histologic lung injury (lung injury score), permeability of the alveolar capillary barrier (lung wet/dry weight ratio and BALF protein concentration) and mortality rates were attenuated in the PALM3 siRNA-treated mice. These results indicate that PALM3 contributes to the development of ALI in mice challenged with LPS. Inhibiting PALM3 through the intranasal application of specific siRNA protected against LPS-induced ALI.     

Regulation of Na,K-ATPase during acute lung injury

A hallmark of acute lung injury is the accumulation of a protein rich edema which impairs gas exchange and leads to hypoxemia. The resolution of lung edema is effected by active sodium transport, mostly contributed by apical Na⁺ channels and the basolateral located Na,K-ATPase. It has been reported that the decrease of Na,K-ATPase function seen during lung injury is due to its endocytosis from the cell plasma membrane into intracellular pools. In alveolar epithelial cells exposed to severe hypoxia, we have reported that increased production of mitochondrial reactive oxygen species leads to Na,K-ATPase endocytosis and degradation. We found that this regulated process follows what is referred as the Phosphorylation–Ubiquitination–Recognition–Endocytosis–Degradation (PURED) pathway. Cells exposed to hypoxia generate reactive oxygen species which activate PKCζ which in turn phosphorylates the Na,K-ATPase at the Ser18 residue in the N-terminus of the α1-subunit leading the ubiquitination of any of the four lysines (K16, K17, K19, K20) adjacent to the Ser18 residue. This process promotes the α1-subunit recognition by the μ2 subunit of the adaptor protein-2 and its endocytosis trough a clathrin dependent mechanism. Finally, the ubiquitinated Na,K-ATPase undergoes degradation via a lysosome/proteasome dependent mechanism.     

Anti-inflammatory effect of octyl gallate in alveolar macrophages cells and mice with acute lung injury

Acute lung injury (ALI) is an inflammatory process, and has high incidence and mortality. ALI and the acute respiratory distress syndrome are two common complications worldwide that result in acute lung failure, sepsis, and death. Pro-inflammatory substances, such as cytokines and chemokines, are responsible for activating the body's defense mechanisms and usually mediate inflammatory processes. Therefore, the research of substances that decrease the uncontrolled response of organism is seen as potential for patients with ALI. Octyl gallate (OG) is a phenolic compound with therapeutic actions namely antimicrobial, antiviral, and antifungal. In this study, we evaluated its action on lipopolysaccharide (LPS)-activated alveolar macrophages RAW 264.7 cells and ALI in male mice. Our results demonstrated protective effects of OG in alveolar macrophages activated with LPS and mice with ALI. The OG treatment significantly decreased the inflammatory markers in both studies in vitro and in vivo. The data suggested that OG can act as an anti-inflammatory agent for ALI.     

Upregulation of hypoxia-induced mitogenic factor in bacterial lipopolysaccharide-induced acute lung injury

Hypoxia-induced mitogenic factor (HIMF), also known as FIZZ1 (found in inflammatory zone), plays important roles in lung inflammation. We found that intraperitoneal injection of lipopolysaccharide (LPS) induced intensive HIMF production exclusively in mouse lung, but not in the heart, liver, spleen or kidney. This HIMF production, at least partly, contributes to LPS-induced vascular cell adhesion molecule-1 (VCAM-1) upregulation and mononuclear cell sequestration to lung parenchyma, while protecting alveolar type II cells from LPS-resulted decrease in surfactant protein-C production and cell death. These data indicate that HIMF participates in LPS-induced acute lung injury and inflammation through modulating VCAM-1 and SP-C expression.     

胃饥饿素对小鼠急性肺损伤的保护作用及其机制研究

目的 探讨胃饥饿素对小鼠急性肺损伤的保护作用和机制.方法 将60只小鼠采用随机数字表法分为6组:对照组、模型组、胃饥饿素低、中、高剂量组和地塞米松组.对照组和模型组腹腔注射0.2 mL生理盐水,胃饥饿素各组分别注射400、200、100 μg/kg溶液,地塞米松组注射2 mg/kg.给药后1h,对照组滴注等体积生理盐水...     

乌司他丁对急性肺损伤/急性呼吸窘迫综合征的治疗研究

目的研究大剂量乌司他丁在急性肺损伤/急性呼吸窘迫综合征中的治疗效果。方法回顾性分析2006年1月至2010年1月广西医科大学第一附属医院ICU收治的154例ALI/ARDS患者的临床资料,根据治疗方案分为乌司他丁组(UTI组)(n=80),对照组(n=74)。记录两组患者开始治疗、治疗第3天、治疗第7天的生命体征、动脉血气分析、血生化检查结果;记录患者在ICU治疗的转归。应用SPSS 13.0软件对结果进行统计学分析。结果经治疗3天UTI组呼吸频率低于对照组;动脉血气分析提示两组患者PaO2、PaO2/Fi O2、SaO2均有上升,UTI组PaO2/Fi O2略低于对照组(P0.01),而两组患者PaO2、SaO2比较无统计学差异。UTI组与对照组的死亡率比较(UTI组52.5%,对照组52.7%,P=0.980)无统计学差异,机械通气时间UTI组低于对照组[UTI组(14.8±3.9)天,对照组(16.7±4.2)天,P=0.020]。根据ALI/ARDS发生的病因分为肺内源性及肺外源性进行亚组分析(A组:肺内源性ALI/ARDS,使用UTI治疗;B组:肺内源性ALI/ARDS,不使用UTI治疗;C组:肺外源性ALI/ARDS,使用UTI治疗;D组:肺外源性ALI/ARDS,不使用UTI治疗),发现乌司他丁对肺外源性ALI/ARDS患者(C组)的ICU时间、ICU内死亡率及机械通气时间均低于不使用UTI的患者(D组)。结论大剂量乌司他丁用于ALI/ARDS的临床治疗可有效改善患者氧合指数,减少机械通气时间,且高血糖的发生率低,尤其是乌司他丁治疗肺外源性ALI/ARDS患者的预后优于肺内源性的ALI/ARDS。     

Protective effects of recombinant 53-kDa protein of Trichinella spiralis on acute lung injury in mice via alleviating lung pyroptosis by promoting M2 macrophage polarization

Trichinella spiralis represents an effective treatment for autoimmune and inflammatory diseases. The effects of recombinant T. spiralis (TS) 53-kDa protein (rTsP53) on acute lung injury (ALI) remain unclear. Here, mice were divided randomly into a control group, LPS group, and rTsP53 + LPS group. ALI was induced in BALB/c mice by LPS (10 mg/kg) injected via the tail vein. rTsP53 (200 µl; 0.4 μg/μl) was injected subcutaneously three times at an interval of 5 d before inducing ALI in the rTsP53+LPS group. Lung pathological score, the ratio and markers of classic activated macrophages (M1) and alternatively activated macrophages (M2), cytokine profiles in alveolar lavage fluid, and pyroptosis protein expression in lung tissue were investigated. RTsP53 decreased lung pathological score. Furthermore, rTsP53 suppressed inflammation by increasing IL-4, IL-10, and IL-13. There was an increase in alveolar M2 macrophage numbers, with an increase in CD206 and arginase-1-positive cells and a decrease in alveolar M1 markers such as CD197 and iNOS. In addition, the polarization of M2 macrophages induced by rTsP53 treatment could alleviate ALI by suppressing lung pyroptosis. RTsP53 was identified as a potential agent for treating LPS-induced ALI via alleviating lung pyroptosis by promoting M2 macrophage polarization.     

C型钠尿肽及其受体在急性肺损伤大鼠肺组织的表达变化及其意义

目的了解C型钠尿肽及其受体NPRB在急性肺损伤大鼠肺组织中的表达变化规律。方法采用LPS注射建立ALI大鼠动物模型。将动物分为生理盐水组(N组),LPS干预1 h组(LPS 1 h组),LPS干预3 h组(LPS 3 h组),LPS干预6 h组(LPS 6 h组),通过RT-PCR检测各组大鼠肺组织CNP及NPRB mRNA的表达情况,以及免疫组化检测各组大鼠NPRB的表达变化,以生理盐水组作为阴性对照。结果正常大鼠肺组织可表达CNP及NPRB,LPS干预后,CNP显著升高,LPS 6 h达到高峰,与对照组比较有显著性差异(P0.05);相反,NPRB在LPS干预后出现表达降低,与对照组比较有显著性差异(P0.05)。结论CNP与NPRB的表达变化可能是导致肺损伤加重的重要原因之一。     

Lung-protective effect of Punicalagin on LPS-induced acute lung injury in mice

Background: Punicalagin (Pun) is one of the main bioactive compounds in pomegranate peel, it possesses many properties, including antioxidant, anti-inflammation and immunosuppressive activities. The study was aimed to investigate the protective effect and mechanisms of Pun on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.Methods and Results: Forty-eight BALB/c male mice were used to establish ALI by intratracheal-instilled 2.4 mg/kg LPS, the mice were randomly divided into model and Pun (10, 20, 40 mg/kg) groups. The other 12 mice were intratracheal-instilled same volume of water as control. After 2 h of receiving LPS, mice were administered drug through intraperitoneal injection. Lung index, histopathological changes, white blood cells and biomarkers in bronchoalveolar lavage fluid (BALF) were analyzed. The protein expression of total and phosphor p65, IκBα, ERK1/2, JNK and p38 in lung tissue was detected. The result showed that Pun could reduce the lung index and wet/dry weight (W/D) ratio, improve lung histopathological injury. In addition, Pun decreased the inflammation cells and regulated the biomarkers in BALF. Furthermore, Pun dose-dependently reduced the phosphor protein levels of p65, IκBα, ERK1/2, JNK and p38 in lung tissue, which exhibited that the effect of Pun related to mitogen-activated protein kinases (MAPKs) pathway. More importantly, there was no toxicity was observed in the acute toxicity study of Pun.Conclusion: Pun improves LPS-induced ALI mainly through its anti-inflammatory properties, which is associated with nuclear factor-κB (NF-κB) and MAPKs signaling pathways. The study implied that Pun maybe a potent agent against ALI in future clinic.     

内皮祖细胞对急性肺损伤保护作用的研究进展

内皮祖细胞（EPC）是一种多潜能细胞,主要来源于骨髓。外周血EPC可以参与修复多种血管内皮细胞损伤的疾病。目前研究证实EPC通过动员、迁移、归巢和分化等步骤在受损的肺组织处参与内皮细胞修复,调节失控的炎症反应,增强抗氧化能力,对修复和维持肺泡毛细血管屏障的完整性起着重要作用。EPC在心血管疾病和组织工程领域应用研究的成功,为EPC在急性肺损伤的治疗提供了新的思路。     

复方清下汤对脓毒症大鼠细胞因子白介素-1、白介素-6调控及肺损伤的作用

目的盲肠结扎穿孔导致大肠埃希菌腹膜炎进而建立脓毒症肺损伤大鼠模型,检测炎性反应时,细胞因子的调控变化,探讨肺水肿的形成机制。经复方清下汤处理后检测上述变化。方法将健康SD大鼠随机分为4组,每组10只:假手术组(SHAM组),只翻动盲肠,不做其他处理;脓毒血症肺损伤组(模型组),盲肠结扎穿孔诱发急性肺损伤(ALI)模型;盲肠结扎穿孔+复方清下汤组(造模后立即灌胃给药,造模后8 h再次灌胃1次,剂量:10 ml/kg);盲肠结扎穿孔+头孢哌酮舒巴坦组(抗生素舒普深)(造模后立即静脉注射1次,造模后8 h再次静脉注射1次,剂量:0.2 g/kg),造模24 h后收集标本。分别观察大鼠的一般状态,留取下腔静脉血清进行白介素-1(IL-1)、白介素-6(IL-6)的测定。镜下观察肺组织病理形态学改变,测量肺湿/干比值的变化。结果与SHAM组比较,模型组IL-1、IL-6水平明显升高(P0.01),肺间质和肺泡内水肿,伴大量红细胞渗出(出血)和纤维素沉积,肺泡间隔毛细血管内皮细胞高度肿胀。肺湿/干比值明显增加(P0.01),抗生素及中药处理组与模型组比较,IL-1、IL-6水平明显降低(P0.01),肺湿/干比值明显降低(P0.01),肺组织镜下表现:中药处理组及抗生素组组较模型组肺泡间隔变窄,毛细血管内皮细胞肿胀减轻,出血减轻,纤维素渗出明显减少。结论实验应用放免检测、显微镜观察以及称量肺湿/干比值等手段,进一步证实了脓毒血症大鼠肺损伤时血清中主要的炎性细胞因子IL-1、IL-6过度表达的情况,并从病理学角度,证实炎性介质的过度表达是造成脓毒症肺损伤的重要原因。经复方清下汤处理的动物模型得到相反结论,为治疗脓毒血症大鼠肺损伤提供一个可能的新的手段。     

血必净对大鼠急性肺损伤的保护作用

目的：研究血必净对急性肺损伤大鼠的保护作用。方法：60只Wistar大鼠随机分为正常组、模型组、地塞米松（10 mg/kg）组与血必净低、中、高剂量（5、10、15 ml/kg）组,每组10只。通过腹腔注射5 mg/kg内毒素建立大鼠急性肺损伤模型,模型成功4 h后腹腔注射给药,每天1次,连续7 d;正常对照组和ALI模型组静脉注射等体积的生理盐水。7 d后采集动脉血,检测动脉血氧分压（PaO₂）、血清丙二醛（MDA）浓度和超氧化物歧化酶（SOD）的活性;取肺组织,检测肺系数（LI）、左肺湿/干质量比（W/D）、肺含水率[（W-D）/W],检测肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）和高迁移率族蛋白-1（HMGB1）蛋白的表达。结果：与正常对照组比较,模型组大鼠LI、W/D、（W-D）/W,TNF-α和HMGB1蛋白表达以及血清MDA含量升高,PaO₂,IL-10蛋白表达和血清SOD活性减弱,差异有统计学意义（P < 0.01）;与模型组比较,血必净低、中、高剂量组大鼠LI、W/D及（W-D）/W,TNF-α和HMGB1蛋白表达以及血清MDA含量降低,PaO₂,IL-10蛋白表达和血清SOD活性增强,差异有统计学意义（P < 0.01）,其中血必净高剂量组效果较好,与中、低剂量组比较,差异有统计学意义（P < 0.05,P < 0.05）。结论：血必净能减轻对内毒素诱导的急性肺损伤,其药理机制可能与下调TNF-α和HMGB1蛋白表达和血清MDA水平和上调IL-10蛋白表达和血清SOD活性有关,且以高剂量组效果较好。