CB2受体激动剂JWH133对百草枯中毒致急性肺损伤大鼠的保护作用

 目的:研究大麻素CB2受体激动剂JWH133对百草枯中毒致急性肺损伤大鼠的保护作用。方法: 72只SD雄性大鼠随机平均分成4组。百草枯中毒组：按照20 mg/kg剂量腹腔注射;低剂量JWH133预处理组：在给予百草枯腹腔注射前1 h腹腔注射5 mg/kg JWH133;高剂量JWH133预处理组：在给予百草枯腹腔注射前1 h腹腔注射20 mg/kg JWH133;正常对照组：1 mL生理盐水腹腔注射。在注射百草枯后8 h、1 d和3 d时,收集动脉血、肺泡灌洗液和肺组织标本。采用血气分析仪测定动脉血氧分压（PaO2）,采用ELISA方法检测支气管肺泡灌洗液中IL-1β和TNF-α含量,行组织切片HE染色进行肺损伤评分,利用Western blotting方法检测肺组织中NF-κB和AP-1 蛋白表达水平。结果: 与正常对照组相比,百草枯中毒组大鼠的动脉血PaO2明显下降,肺组织结构破坏,肺泡间质水肿,肺损伤指数增加,支气管肺泡灌洗液中炎性细胞因子IL-1β和TNF-α含量明显增加。JWH133预处理,尤其是高剂量JWH133可以减轻肺组织损伤程度,降低支气管肺泡灌洗液中IL-1β和TNF-α含量,减少肺组织中NF-κB和AP-1 蛋白的表达。结论: 应用CB2受体激动剂JWH133可以抑制百草枯中毒大鼠肺组织中NF-κB和AP-1 蛋白的表达,减少炎性细胞因子IL-1β和TNF-α的分泌,减轻百草枯中毒导致的急性肺损伤。     

油酸-脂多糖介导大鼠急性肺损伤及肺组织AP-1活性的变化

本文探讨了在油酸－内毒素（OA＋LPS）介导的大鼠急性肺损伤（ALI）模型肺组织中，转录因子AP－1活性变化的意义。有用OA＋LPS序贯性两次致伤，复制ALI大鼠模型；采用凝胶迁移率分析法（EMSA）检测肺组织AP－1活性。结果显示：OA＋LPS模型组大鼠呼吸窘迫，PaO2早期低于8kPa，死亡率升高，肺含水量显著增加，肺水肿、浸润等病变严重，伴透明膜形成，肺组织AP－1活性显著升高；并且，间隔4h两次致伤后，P aO2降低幅度最大，死亡率高达78.57%，肺含水量最大，肺病理改变最重，肺组织AP－1活性最高。结果表明：OA＋LPS序贯性两次致伤，可以介导大鼠发生严重的ALI；ALI的发生、发展与AP－1活性异常升高有关。     

褪黑素预处理对抗油酸引起的大鼠急性肺损伤

目的：评估褪黑素预处理对油酸引起的大鼠急性肺损伤的拮抗作用。方法：24只大鼠随机分为生理盐水组、油酸组和褪黑素预处理组3组，检测大鼠肺泡灌洗蛋白、肺的湿干比重、丙二醛、超氧化物岐化酶水平，并进行肺的病理组织学检查。结果：（1）静脉注射0.15 mL/kg油酸引起肺泡灌洗蛋白、肺的湿干比重显著增高（P<0.01），病理组织学检查发现有肺出血、肺水肿、肺泡间隔增厚以及肺泡腔出现炎性细胞，导致严重的急性肺损伤；（2）提前60 min腹腔注射20 mg/kg褪黑素明显减轻上述的症状，与丙二醛的降低（P<0.01）和超氧化物岐化酶的升高（P<0.01）相一致。结论：褪黑素预处理可通过清除和防止自由基的形成，进一步降低肺泡毛细血管膜通透性的增加，从而减轻油酸引起的大鼠急性肺损伤。提示褪黑素可能在急性肺损伤的防治中是有效的。     

Suppression of MAPK and NF-κB Pathways by Limonene Contributes to Attenuation of Lipopolysaccharide-Induced Inflammatory Responses in Acute Lung Injury

The present study aimed to investigate the protective role of limonene in lipopolysaccharide (LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS (0.5 mg/kg), and limonene (25, 50, and 75 mg/kg) was injected intraperitoneally 1 h prior to LPS administration. After 12 h, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Limonene pretreatment at doses of 25, 50, and 75 mg/kg decreased LPS-induced evident lung histopathological changes, lung wet-to-dry weight ratio, and lung myeloperoxidase activity. In addition, pretreatment with limonene inhibited inflammatory cells and proinflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. Furthermore, we demonstrated that limonene blocked the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase in LPS-induced ALI. The results presented here suggest that the protective mechanism of limonene may be attributed partly to decreased production of proinflammatory cytokines through the inhibition of NF-κB and MAPK activation.     

中性粒细胞胞外诱捕网在新生大鼠急性肺损伤中的作用

目的:探讨中性粒细胞胞外诱捕网(NETs)在新生大鼠急性肺损伤(ALI)中的作用。方法:取出生7 d的SD大鼠30只,按照随机数字表法分成生理盐水对照组、ALI组及ALI+脱氧核糖核酸酶(Dnase)组,每组10只。ALI组用脂多糖(LPS)以20 mg/kg的剂量腹腔注射,ALI+Dnase组则在注射LPS后即腹腔注射Dnase(5 mg/kg)。给药6 h后,水合氯醛麻醉大鼠,收集支气管肺泡灌洗液(BALF),荧光酶标仪检测BALF中游离DNA(cf-DNA)的含量;右肺组织固定于4%多聚甲醛中,HE染色观察各组大鼠肺组织形态结构;左肺组织制备肺组织匀浆,酶联免疫吸附测定(ELISA)法检测肺组织匀浆中白细胞介素6(IL-6)及肿瘤坏死因子α(TNF-α)的含量;使用免疫荧光法与Western blot检测各组大鼠肺组织中瓜氨酸化组蛋白H3(CitH3)及髓过氧化物酶(MPO)的生成情况。结果:与对照组相比,ALI组与ALI+Dnase组中cf-DNA、CitH3、MPO、IL-6及TNF-α水平均升高(P<0.05),肺组织中炎性细胞浸润严重;与ALI组相比,ALI+Dnase组新生大鼠肺组织中cf-DNA、Cith3、MPO、IL-6及TNF-α水平降低(P<0.05),ALI+Dnase组炎症浸润程度降低。结论:新生大鼠ALI中,NETs水平为反映肺组织损伤的重要指标,NETs可能为治疗新生儿ALI的新靶点。     

Galantamine protects against lipopolysaccharide-induced acute lung injury in rats

Lipopolysaccharide (LPS)-induced endotoxemia triggers the secretion of proinflammatory cytokines and can cause acute lung injury (ALI). The high mobility group box 1 (HMGB1) protein plays an important role as a late mediator of sepsis and ALI. Galantamine (GAL) is a central acetylcholinesterase inhibitor that inhibits the expression of HMGB1. This study evaluated the effects of GAL by measuring levels of inflammatory mediators and observing histopathological features associated with LPS-induced ALI. Sixty 8-10 week old male Sprague-Dawley rats (200-240 g) were randomized into three groups as follows: control group, LPS group (7.5 mg/kg LPS), and LPS+GAL group (5 mg/kg GAL before LPS administration). Histopathological examination of lung specimens obtained 12 h after LPS administration was performed to analyze changes in wet-to-dry (W/D) weight ratio, myeloperoxidase (MPO) activity, and HMGB1 expression level. Additionally, plasma concentrations of tumor necrosis factor-α, interleukin-6, and HMGB1 were measured using an enzyme-linked immunosorbent assay at 0 (baseline), 3, 6, 9, and 12 h after LPS administration. Mortality in the three groups was recorded at 72 h. LPS-induced ALI was characterized by distortion of pulmonary architecture and elevation of MPO activity, W/D weight ratio, and levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-6, and HMGB1. Pretreatment with GAL significantly reduced the LPS-induced lung pathological changes, W/D weight ratio, levels of pro-inflammatory cytokines and MPO activity (ANOVA). Moreover, GAL treatment significantly decreased the mortality rate (ANOVA). In conclusion, we demonstrated that GAL exerted a protective effect on LPS-induced ALI in rats.     

Bark extract of Bathysa cuspidata attenuates extra-pulmonary acute lung injury induced by paraquat and reduces mortality in rats

This study investigated the effect of the bark extract of Bathysa cuspidata on paraquat (PQ)-induced extra-pulmonary acute lung injury (ALI) and mortality in rats. ALI was induced with a single dose of PQ (30 mg/kg, i.p.), and animals were treated with B. cuspidata extract (200 and 400 mg/kg). Analyses were conducted of survival, cell migration, lung oedema, malondialdehyde, proteins carbonyls, catalase, superoxide dismutase, histopathology and the stereology of lung tissue. Rats exposed to PQ and treated with 200 and 400 mg of the extract presented lower mortality (20% and 30%), compared with PQ alone group (50%). Furthermore, lung oedema, septal thickening, alveolar collapse, haemorrhage, cell migration, malondialdehyde and proteins carbonyl levels decreased, and catalase and superoxide dismutase activity were maintained. These results show that the bark extract of B. cuspidata reduced PQ-induced extra-pulmonary ALI and mortality in rats and suggest that these effects may be associated with the inhibition of oxidative damage.     

阿托伐他汀对百草枯中毒大鼠肺纤维化的影响及机制研究

目的观察阿托伐他汀对急性百草枯(PQ)中毒大鼠肺间质成纤维细胞中基质金属蛋白酶及Smad3的表达影响,探讨其在PQ中毒致肺纤维化中的意义。方法 SD大鼠105只,随机分为对照组15只、百草枯组45只、阿托伐他汀组45只,后2组按时间点又随机分为3组。百草枯组、阿托伐他汀腹腔内注射百草枯35 mg/kg,对照组注射等体积无菌生理盐水,阿托伐他汀组给与阿托伐他汀1.5 mg/(kg.d)灌胃治疗。7、14、21 d后分离和提取肺间质成纤维细胞。采用RT-PCR检测肺组织MMP-2 mRNA、MMP-9 mRNA及Smad3 mRNA的表达。应用免疫细胞化学观察MMP-2、MMP-9、TGF-β1及用碱水解法检测HYP的表达量,观察肺病理学变化。结果与百草枯中毒比较,阿托伐他汀组MMP-2 mRNA、MMP-9 mRNA、Smad3 mRNA表达减少,MMP-2、MMP-9表达也减少,TGF-β1、HYP显著降低,具有统计学意义(P<0.05);病检发现:阿托伐他汀组炎细胞减少,可见成纤维细胞,周围较多正常肺组织,肺纤维化较白草枯中毒组明显减轻。结论阿托伐他汀具有抑制MMP-2 mRNA及MMP-9 mRNA的表达,进而减少MMP-2及MMP-9的表达,抑制Smad3 mRNA的表达,使TGF-β1及HYP生成减少,使肺间质纤维化明显减轻。     

Effect of Methylsulfonylmethane on Paraquat-Induced Acute Lung and Liver Injury in Mice

Methylsulfonylmethane (MSM) is a natural organosulfur compound that exhibits antioxidative and anti-inflammatory effects. This study was carried out to investigate the effect of MSM on paraquat (PQ)-induced acute lung and liver injury in mice. A single dose of PQ (50 mg/kg, i.p.) induced acute lung and liver toxicity. Mice were treated with MSM (500 mg/kg/day, i.p.) for 5 days. At the end of the experiment, animals were euthanized, and lung and liver tissues were collected for histological and biochemical analysis. Tissue samples were used to determine malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and tumor necrosis factor-α (TNF-α) levels. Blood samples were used to measure plasma alanine transaminase (ALT), γ-glutamyl transferase (GGT), and alkaline phosphatase (ALP). Histological examination indicated that MSM decreased lung and liver damage caused by PQ. Biochemical results showed that MSM treatment significantly reduced tissue levels of MDA, MPO, and TNF-α, while increased the levels of SOD, CAT, and GSH compared with PQ group. MSM treatment also significantly reduced plasma levels of ALT, GGT, and ALP. These findings suggest that MSM as a natural product attenuates PQ-induced pulmonary and hepatic oxidative injury.     

Picrotoxin enhances latent extinction of conditioned fear

Male CD1 mice received 20 pairings of tone and footshock (FS) or tone alone in an arm of a Y-maze on Day 1. On Day 2 either extinction (tone alone) or no extinction was followed immediately by saline or picrotoxin (0.5 or 1.0 mg/kg ip). Nonextinguished groups received only saline or picrotoxin (1.0 mg/kg ip) on Day 2. Other groups received saline or picrotoxin (1.0 mg/kg) 2 hr after extinction. On Day 3 all mice were placed in the Y-maze (with doors to all 3 alleys open), and total alley entries during a 2-min test session were recorded. Day 1 FS training resulted in reduced alley entries during the test session. Day 2 extinction session significantly attenuated the effects of the FS training. Day 3 performance of mice given picrotoxin (1.0 but not 0.5 mg/kg) immediately postextinction was comparable to that of mice not given FS on Day 1. The findings suggest that picrotoxin enhanced extinction of conditioned fear.     

基于Nrf2通路探讨阿里红三萜酸减轻脂多糖诱导的小鼠急性肺损伤的作用

目的:探讨阿里红总三萜酸(Fomes officinalis Ames triterpenic acid,FOTa)对脂多糖(lipopolysac?charide,LPS)诱导的小鼠急性肺损伤(acute lung injury,ALI)的预防作用及核因子E2相关因子2(nuclear factor E2-relat...     

The role of aquaporin-1 (AQP1) expression in a murine model of lipopolysaccharide-induced acute lung injury

A murine model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) was used to evaluate whether aquaporin-1 (AQP1) is involved in lung inflammation and lung edema formation. Swiss strain mice (n = 122) had LPS (5 mg/kg) instilled intratracheally (IT), and were then treated with either 0.9 % saline or dexamethasone (5 mg/kg/day). Mice were euthanized at 2 days and 7 days after treatment. Inflammatory cytokines (TNF-alpha, IL-6), protein concentration in bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, histology, immunohistochemistry, and AQP1 Western blot were performed. Lung wet-to-dry weight ratio and lung vascular permeability were also measured in the AQP1 knockout mice (n = 9) that received IT LPS (5 mg/kg) at 2 days. Intratracheal instillation of LPS produced a severe lung injury at 2 days, characterized by elevation of TNF-alpha, IL-6 in the BAL fluid, and by histological changes consistent with increased lung vascular permeability and neutrophil infiltration. AQP1-immunoreactivity in the pulmonary capillary endothelium was reduced at 2 days and 7 days. Administration of dexamethasone improved LPS-induced ALI and retained expression of AQP1. However, depletion of AQP1 did not affect lung edema formation, lung vascular permeability, or lung histology. The results suggest that although AQP1 expression is decreased after lung injury, depletion of AQP1 does not alter lung inflammation and lung edema induced by LPS.     

气道给rhSOD对胎粪诱导肺损伤中NF-κB及MIP-1α表达的影响

目的：观察早期经气道给予重组人超氧化物歧化酶（rhSOD）对胎粪诱导大鼠肺NF-κB和炎症因子MIP-1α表达的影响，以探讨其在胎粪诱导肺损伤中的作用及其机制。 方法： 24只雄性SD大鼠，随机分为：（1）对照组（control）,经气管插管注入生理盐水1 mL/kg；（2）胎粪+生理盐水处理组（Mec/saline）；（3）胎粪+ rhSOD治疗组(Mec/rhSOD)。后两者先由气管插管注入20%新生儿胎粪生理盐水混悬液1 mL/kg建立急性肺损伤模型，再分别经气管插管注入生理盐水1 mL/kg或rhSOD 20 g·L-1·kg-1。24 h后取材， RT-PCR法测定肺组织MIP-1α mRNA、Western blotting法测定NF-κB蛋白表达改变，同时行支气管肺泡灌洗液（BAL）细胞计数。 结果： Mec/saline组大鼠BAL细胞计数、肺组织MIP-1α mRNA和NF-κB蛋白表达均明显高于control组［(4.68±1.40)×109 cells/L vs (0.53±0.19)×109 cells/L, 3.60±0.75 vs 1.56±0.33， 0.72±0.31 vs 0.23±0.21］，（均P<0.01）； Mec/rhSOD组大鼠BAL细胞计数、肺组织MIP-1α mRNA和NF-κB蛋白表达分别为(3.13±0.77)×109cells/L、2.20±0.39和0.44±0.21，均显著低于Mec/saline组（均P<0.01），但仍显著高于control组（均P<0.01）。 结论： 早期经气道给rhSOD可能通过抑制肺MIP-1α和NF-κB表达而减轻胎粪诱导的肺炎症反应。     

Protective effect of Xuebijing injection on paraquat-induced pulmonary injury via down-regulating the expression of p38 MAPK in rats

Background

Exposure to paraquat results in acute lung injury. A systemic inflammatory response has been widely established as a contributor to paraquat-induced acute lung injury. Recent studies have reported that consumption of Xuebijing prevents inflammatory response-induced diseases. This study investigated whether consumption of Xuebijing protected rats against paraquat-induced acute lung injury.

Methods

Adult male Sprague Dawley rats were randomly divided into four groups: control group; paraquat group; paraquat?+?Xuebijing group; and paraquat?+?dexamethasone group. Rats in the paraquat, paraquat?+?Xuebijing and paraquat?+?dexamethasone groups were intraperitoneally injected with paraquat (30 mg/kg) or administered paraquat and Xuebijing at 8 mL/kg or dexamethasone at 5 mg/kg, respectively, via an injection into the tail vein. Lung p38 MAPK, NF-κB65, IkB, p-IκB-α, HIF-1α, Nrf2 and TGF-β1 expression were essayed using western blotting. IL-6, TNF-α, IL-1β, IL-10, TGF-β1 and PIIIP were measured using ELISA. ROS, oxidised glutathione and glutathione activity were measured.

Results

After inducing acute lung injury with paraquat for 24 h, Xuebijing was observed to block lung p-p38 MAPK, NF-κB65, HIF-1α, p-IκB-α and TGF-β1 expression, and increased Nrf2 and IkB expression. The numbers of neutrophils and lymphocytes and total number of cells were significantly lower in the Xuebijing group compared with the control group. IL-6, TNF-α, IL-1β, TGF-β1 and PIIIP levels were significantly decreased in the Xuebijing group. ROS and oxidised glutathione activity were markedly inhibited by Xuebijing. Histological evaluation showed attenuation of the effects of Xuebijing on paraquat-induced lung injury. Compared with the paraquat?+?dexamethasone group, the Xuebijing?+?paraquat group showed no significant differences.

Conclusions

Inhibiting the expression of p38 MAPK and NF-κB65 was crucial for the protective effects of Xuebijing on paraquat-induced acute lung injury. The findings suggest that Xuebijing could effectively ameliorate paraquat-induced acute lung injury in rats. Xuebijing was as effective as dexamethasone at improving paraquat-induced lung injury by regulating lung inflammation, lung function and oxidative stress responses.

     

过氧化物酶增殖体激活受体α在急性肺损伤大鼠肺组织的表达及其意义

目的: 观察内毒素(LPS)复制的急性肺损伤（ALI）大鼠肺组织过氧化物酶增殖体激活受体α（PPARα）表达的变化,探讨PPARα在ALI中可能的作用。方法: 将40只雄性Wistar大鼠随机分为对照组、LPS致伤1 h组、2 h组、4 h组和8 h组。用LPS(5 mg/kg) 静脉注射复制大鼠ALI模型，分别在LPS致伤后1 h、2 h、4 h、8 h时处死大鼠，测定各组肺组织湿/干重比（W/D）及肺组织病理变化；采用RT-PCR法检测肺组织中PPARα mRNA的表达；采用免疫组化法检测肺组织中PPARα的表达。结果: LPS致伤后2 h、4 h、8 h肺组织W/D均显著高于对照组（均P< 0.01）；LPS致伤后2h、4h PPARα mRNA表达分别显著低于对照组（均P < 0.01）；而LPS致伤4h和8h组PPARα表达阳性细胞数显著低于对照组（均P< 0.05）。结论: PPARα在ALI大鼠肺组织表达降低。表明PPARα在急性肺损伤的发病机制中具有重要作用。     

联合应用氨溴索与小剂量肝素对急性肺损伤ICAM-1和EP-selectin的影响

目的: 制作急性肺损伤(ALI)模型并检测细胞间黏附分子-1(ICAM-1)、E-选择素和P-选择素在实验兔血清、肺组织及支气管肺泡灌洗液(BALF)中的变化情况以探讨三者在ALI中的作用并观察联合应用氨溴索与小剂量肝素对其的影响。方法: 24只健康兔随机分成3组:对照组(NC组),油酸损伤组(OA组),氨溴索＋小剂量肝素治疗组(AH组)。采用耳缘静脉法静注油酸复制兔ALI模型,检测各组动脉氧分压(PaO₂),ELISA法检测ICAM-1和E-选择素,TUNEL法检测凋亡指数(AI),免疫组化检测P-选择素,电镜观察肺组织超微结构变化并测定湿干重比值(W/D)。结果: 与NC组比较, OA组和AH组PaO₂显著降低(P<0.01),但AH组显著高于OA组(P<0.01); ICAM-1、E-选择素的浓度(血清、肺组织及BALF中)、肺组织AI和W/D升高(P<0.05或P<0.01),但AH组低于OA组(P<0.05或P<0.01)。与同组给予治疗药物前0 h比较,NC组无差异(P>0.05),OA组各时点PaO₂显著降低(P<0.01),ICAM-1和E-选择素浓度显著升高(P<0.01),AH组各时点PaO₂降低(P<0.05)、ICAM-1和E-选择素浓度升高(P<0.05)。肺组织中P-选择素在OA组表达较为广泛:主要为炎症细胞、毛细血管的内皮细胞和血管内的血浆等,NC组呈低水平表达,AH组的表达介于两者之间。细胞凋亡以OA组最为明显,NC组未见细胞凋亡或偶有凋亡,AH组凋亡的细胞明显比OA组减少。结论: 在OA致ALI时,ICAM-1、E-选择素和P-选择素明显增高,参与了ALI的发生、发展;联合应用氨溴索与小剂量肝素可以降低ICAM-1、E-选择素和P-选择素的水平,减轻肺脏细胞的损伤、改善肺通气和换气功能、减轻肺水肿,从而发挥对ALI的防治作用。     

Quercetin protects against lipopolysaccharide-induced acute lung injury in rats through suppression of inflammation and oxidative stress

Introduction

Acute lung injury (ALI) is an acute inflammatory disease characterized by excess production of inflammatory factors in lung tissue. Quercetin, a herbal flavonoid, exhibits anti-inflammatory and anti-oxidative properties. This study was performed to assess the effects of quercetin on lipopolysaccharide (LPS)-induced ALI.

Material and methods

Sprague-Dawley rats were randomly divided into 3 groups: the control group (saline alone), the LPS group challenged with LPS (Escherichia coli 026:B6; 100 µg/kg), and the quercetin group pretreated with quercetin (50 mg/kg, by gavage) 1 h before LPS challenge. Bronchoalveolar lavage fluid (BALF) samples and lung tissues were collected 6 h after LPS administration. Histopathological and biochemical parameters were measured.

Results

The LPS treatment led to increased alveolar wall thickening and cellular infiltration in the lung, which was markedly prevented by quercetin pretreatment. Moreover, quercetin significantly (p < 0.05) attenuated the increase in the BALF protein level and neutrophil count and lung wet/dry weight ratio and myeloperoxidase activity in LPS-challenged rats. The LPS exposure evoked a 4- to 5-fold rise in BALF levels of tumor necrosis factor-α and interleukin-6, which was significantly (p < 0.05) counteracted by quercetin pretreatment. Additionally, quercetin significantly (p < 0.05) suppressed the malondialdehyde level and increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in the lung of LPS-treated rats.

Conclusions

Quercetin pretreatment effectively ameliorates LPS-induced ALI, largely through suppression of inflammation and oxidative stress, and may thus have therapeutic potential in the prevention of this disease.     

藤黄酸减轻脂多糖诱导的小鼠急性肺损伤

目的探讨藤黄酸(GA)对脂多糖(LPS)所致小鼠急性肺损伤的保护作用及其机制。方法采用尾静脉注射LPS(4 mg/kg)建立小鼠急性肺损伤模型。实验将小鼠随机分为对照组(control组)、模型组(model组)、藤黄酸组(GA组)和藤黄酸预处理组(GA+LPS组),6 h后测定肺湿/干重比值(W/D);检测髓过氧化物酶(MPO)活性;检测肺泡灌洗液(BALF)中蛋白含量和白细胞计数;ELISA检测肺匀浆中白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量。结果模型组小鼠肺W/D、MPO活性、BALF中蛋白含量和白细胞数量均增加,肺组织IL-1β和TNF-α水平升高(均P0.01);藤黄酸预处理可减轻LPS引起的以上指标变化(均P0.05)。结论 GA可减轻LPS诱导的急性肺损伤,其机制可能与降低肺组织IL-1β和TNF-α的含量、抑制中性粒细胞在肺部的聚集和减轻肺部水肿相关。