The effects of the combination of sodium ferulate and oxymatrine on lipopolysaccharide-induced acute lung injury in mice

In our previous study, the remarkable analgesic and anti-inflammatory effects of the combination of sodium ferulate (SF) and oxymatrine (OMT) had been found. In this study, we investigated the effect of the combination of SF and OMT on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting and the protein concentration in the bronchoalveolar lavage fluid (BALF) were measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators including C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were assayed by enzyme-linked immunosorbent assay method. The data showed that treatment with the combination of SF and OMT markedly attenuated inflammatory cell numbers and protein concentration in the BALF and improved SOD activity and inhibited MPO activity compared to LPS group. Moreover, the combination significantly inhibited the production of CRP and TNF-α in lung homogenate. The histological changes of the lungs were also more significantly improved by the combination. At the same dose, the obvious protective effect was not found in SF or OMT-treated alone group except that the protein concentration slightly decreased in SF group. The results indicated that the combination SF and OMT had a protective effect on LPS-induced ALI in mice, and the effect was much better than that of SF or OMT used alone.     

Azilsartan attenuates lipopolysaccharide-induced acute lung injury via the Nrf2/HO-1 signaling pathway

Acute lung injury (ALI) is a severe complication of sepsis and hemorrhagic shock with high morbidity. In the present study, the protective effect of Azilsartan on lipopolysaccharide (LPS)-induced ALI in mice was investigated to explore the potential therapeutic property of Azilsartan for the treatment of ALI. LPS was used to induce an ALI model in mice. Hematoxylin–eosin (HE) staining sections were then evaluated for the pathological state of lung tissues. Bronchoalveolar lavage fluid (BALF) protein concentration, wet/dry weight ratios of lung tissues, and pulmonary myeloperoxidase (MPO) activity were detected to determine the degree of pulmonary injury. The number of total cells, macrophages, and neutrophils in BALF were counted using a hemocytometer to illustrate the inflammatory cell infiltration. The lung function was monitored using a spirometer. The concentrations of interleukin-1β (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) were determined using enzyme-linked immunosorbent assay (ELISA). Oxidative stress was evaluated by the superoxide dismutase (SOD) activity, glutathione (GSH), and malondialdehyde (MDA) concentrations in the lung tissue. The expressions of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were determined using Western blot analysis. Azilsartan therapy alleviated LPS-induced lung tissue damage, increased BALF protein concentration, lung wet to dry weight ratio, MPO activity, and macrophage and neutrophils infiltration. Also, Azilsartan ameliorated the production of inflammatory factors (IL-1β, MCP-1, and IL-8). Azilsartan ameliorated LPS-impaired lung SOD activity, the GSH concentration, and the MDA concentration. Mechanistically, Azilsartan activated the LPS-impaired Nrf2/HO-1 signaling pathway. Azilsartan therapy attenuates LPS-induced ALI via the Nrf2/HO-1 signaling pathway.

     

Protective Effect of p-Cymene on Lipopolysaccharide-Induced Acute Lung Injury in Mice

In the previous study, the anti-inflammatory effect of p-cymene had been found. In this study, we investigated anti-inflammatory effects of p-cymene on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators including tumor necrosis factor alpha (TNF-α), IL-1β, and IL-6 were assayed by enzyme-linked immunosorbent assay method. The pathological changes of the lung tissues were observed by hematoxylin and eosin staining. The inflammatory signal pathway-related protein levels of NF-κB were measured using Western blotting. The data showed that treatment with the p-cymene markedly attenuated inflammatory cell numbers in the BALF, decreased NF-κB protein level in the lungs, improved SOD activity, and inhibited MPO activity. Histological studies demonstrated that p-cymene substantially inhibited LPS-induced neutrophils in the lung tissue compared with the model group. The results indicated that p-cymene had a protective effect on LPS-induced ALI in mice.     

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。     

亚精胺减轻脂多糖诱导的小鼠急性肺损伤

目的　观察亚精胺（spermidine）对脂多糖（LPS）诱导的急性肺损伤（ALI）的影响。 方法　采用5 mg/kg的LPS经气管滴注,建立ALI小鼠模型。用小动物呼吸机检测亚精胺对ALI小鼠呼吸功能的影响;观察亚精胺对ALI小鼠肺组织形态变化的影响;检测ALI小鼠支气管肺泡灌洗液（BALF）中总蛋白、总细胞数及中性粒细胞数目,并检测髓过氧化物酶（MPO）的水平;qPCR检测ALI小鼠肺组织中TREM-1 mRNA的表达;ELISA检测ALI小鼠BALF中sTREM-1的蛋白水平。 结果　亚精胺可改善ALI小鼠的呼吸功能;减轻LPS诱导的肺部病理损伤;减少蛋白渗出和中性粒细胞浸润;降低ALI小鼠肺内炎症放大受体TREM-1的表达。 结论　亚精胺能减少炎症细胞浸润,抑制炎症因子表达,从而减轻LPS诱导的ALI,其机制可能与亚精胺可抑制ALI小鼠肺组织TREM-1表达有关。     

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.     

亚精胺减轻脂多糖诱导的小鼠急性肺损伤

目的　观察亚精胺（spermidine）对脂多糖（LPS）诱导的急性肺损伤（ALI）的影响。 方法　采用5 mg/kg的LPS经气管滴注,建立ALI小鼠模型。用小动物呼吸机检测亚精胺对ALI小鼠呼吸功能的影响;观察亚精胺对ALI小鼠肺组织形态变化的影响;检测ALI小鼠支气管肺泡灌洗液（BALF）中总蛋白、总细胞数及中性粒细胞数目,并检测髓过氧化物酶（MPO）的水平;qPCR检测ALI小鼠肺组织中TREM-1 mRNA的表达;ELISA检测ALI小鼠BALF中sTREM-1的蛋白水平。 结果　亚精胺可改善ALI小鼠的呼吸功能;减轻LPS诱导的肺部病理损伤;减少蛋白渗出和中性粒细胞浸润;降低ALI小鼠肺内炎症放大受体TREM-1的表达。 结论　亚精胺能减少炎症细胞浸润,抑制炎症因子表达,从而减轻LPS诱导的ALI,其机制可能与亚精胺可抑制ALI小鼠肺组织TREM-1表达有关。     

Fisetin Alleviates Lipopolysaccharide-Induced Acute Lung Injury via TLR4-Mediated NF-κB Signaling Pathway in Rats

Acute lung injury (ALI), a common component of systemic inflammatory disease, is a life-threatening condition without many effective treatments. Fisetin, a natural flavonoid from fruits and vegetables, was reported to have wide pharmacological properties such as anti-inflammatory, antioxidant, and anticancer activities. The aim of this study was to detect the effects of fisetin on lipopolysaccharide (LPS)-induced acute lung injury and investigate the potential mechanism. Fisetin was injected (1, 2, and 4 mg/kg, i.v.) 30 min before LPS administration (5 mg/kg, i.v.). Our results showed that fisetin effectively reduced the inflammatory cytokine release and total protein in bronchoalveolar lavage fluids (BALF), decreased the lung wet/dry ratios, and obviously improved the pulmonary histology in LPS-induced ALI. Furthermore, fisetin inhibited LPS-induced increases of neutrophils and macrophage infiltration and attenuated MPO activity in lung tissues. Additionally, fisetin could significantly inhibit the Toll-like receptor 4 (TLR4) expression and the activation of NF-κB in lung tissues. Our data indicates that fisetin has a protective effect against LPS-induced ALI via suppression of TLR4-mediated NF-κB signaling pathways, and fisetin may be a promising candidate for LPS-induced ALI treatment.     

Formononetin Inhibited the Inflammation of LPS-Induced Acute Lung Injury in Mice Associated with Induction of PPAR Gamma Expression

Formononetin has shown a variety of pharmacologic properties including anti-inflammatory effect. In the present study, we analyzed the role of formononetin in acute lung injury induced by lipopolysaccharide (LPS) in mice. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators, tumor necrosis factor-α (TNF-α) and IL-6,were assayed by enzyme-linked immunosorbent assay method. Pathological changes of hung tissues were observed by HE staining. Peroxisome proliferator-activated receptor (PPAR)-γ gene expression was measured by real-time PCR. The data showed that treatment with the formononetin group markedly attenuated inflammatory cell numbers in the BALF, increased PPAR-γ gene expression and improved SOD activity and inhibited MPO activity. The histological changes of the lungs were also significantly improved by formononetin compared to LPS group. The results indicated that formononetin has a protective effect on LPS-induced acute lung injury in mice.     

Cavidine Ameliorates Lipopolysaccharide-Induced Acute Lung Injury <Emphasis Type="Italic">via</Emphasis> NF-κB Signaling Pathway <Emphasis Type="Italic">in vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis>

Acute lung injury (ALI) is characterized by widespread inflammation in the lungs and alveolar-capillary destruction, causing high morbidity and mortality. Cavidine, isolated from Corydalis impatiens, have been exhibited to have potent anti-inflammatory effects in previous studies. The purpose of this study was to evaluate the protective effect of cavidine on lipopolysaccharide (LPS)-induced ALI and to enunciate the underlying in vivo and in vitro mechanisms. Mice were intraperitoneally administrated with cavidine (1, 3, or 10 mg/kg) at 1 and 12 h, prior to the induction of ALI by intranasal administration of LPS (30 mg/kg). Blood samples, lung tissues, and bronchoalveolar lavage fluid (BALF) were harvested after LPS challenge. Furthermore, we used LPS-induced lung epithelial cells A549 to examine the mechanism of cavidine to lung injury. The results showed that pretreatment with cavidine significantly decreased lung wet-to-dry weight (W/D) ratio, reduced pro-inflammatory cytokine levels including TNF-α and IL-6 in BALF and serum from LPS-stimulated mice, and attenuated lung histopathological changes. In addition, western blot results showed that cavidine inhibited the phosphorylation of nuclear factor-kappaB (NF-κB) p65 and IκBα induced by LPS. In conclusion, our results demonstrate that cavidine protects against LPS-induced acute lung injury in mice via inhibiting of pro-inflammatory cytokine TNF-α and IL-6 production and NF-κB signaling pathway activation. Taken together, cavidine may be useful for the prevention and treatment of pulmonary inflammatory diseases, such as ALI.     

The Effects of Morin on Lipopolysaccharide-Induced Acute Lung Injury by Suppressing the Lung NLRP3 Inflammasome

In previous study, the anti-inflammatory effect of morin had been found. In this study, we investigated anti-inflammatory effects of morin on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting in the bronchoalveolar lavage fluid (BALF) was measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity were assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-18, and IL-6 were assayed by enzyme-linked immunosorbent assay method. Pathological changes of lung tissues were observed by hematoxylin and eosin (HE) staining. The protein level of lung NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome was measured by Western blotting. The data showed that treatment with the morin markedly attenuated inflammatory cell numbers in the BALF, decreased lung NLRP3 inflammasome protein level, and improved SOD activity and inhibited MPO activity. Histological studies demonstrated that morin substantially inhibited LPS-induced neutrophils in lung tissue compared with model group. The results indicated that the morin had a protective effect on LPS-induced ALI in mice.     

Protocatechuic acid attenuates lipolysaccharide-induced acute lung injury

Protocatechuic acid (PCA) is a major metabolite of anthocyanins. It has numerous pharmacological effects, including anti-inflammatory, antioxidant, and antitumoral activities. In the present study, we investigated the in vivo protective effect of PCA on acute lung injury (ALI) induced by lipolysaccharide (LPS) in mice. We treated mice with PCA 1 h before the intratracheal (i.n.) administration of LPS. The pulmonary injury severity was evaluated 6 h after LPS administration. We found that pretreatment with a 30 mg/kg of PCA markedly attenuated the LPS-induced histological alterations in the lung. In addition, PCA inhibited the production of several inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and IL-6, at 6 h in the bronchoalveolar lavage fluid (BALF) after LPS challenge. Furthermore, PCA significantly reduced the number of total cells, neutrophils, and macrophages in the BALF, and it significantly decreased the wet/dry weight (W/D) ratio of lungs and the protein concentration in the BALF. Additionally, Western blotting showed that PCA efficiently blunted nuclear factor-kappa B (NF-κB) activation by inhibiting the degradation and phosphorylation of IκBα, as well as the translocation of p65 from cytoplasm to the nucleus. In conclusion, these results indicate that PCA was highly effective in inhibiting acute lung injury (ALI) and may be a promising potential therapeutic reagent for ALI treatment. PCA may utilize the NF-κB pathway to attenuate the nonspecific pulmonary inflammation induced by LPS administration.     

Protective Effect of Amygdalin on LPS-Induced Acute Lung Injury by Inhibiting NF-κB and NLRP3 Signaling Pathways

The acute lung injury (ALI) is a leading cause of morbidity and mortality in critically ill patients. Amygdalin is derived from the bitter apricot kernel, an efficacious Chinese herbal medicine. Although amygdalin is used by many cancer patients as an antitumor agent, there is no report about the effect of amygdalin on acute lung injury. Here we explored the protective effect of amygdalin on ALI using lipopolysaccharide (LPS)-induced murine model by detecting the lung wet/dry ratio, the myeloperoxidase (MPO) in lung tissues, inflammatory cells in the bronchoalveolar lavage fluid (BALF), inflammatory cytokines production, as well as NLRP3 and NF-κB signaling pathways. The results showed that amygdalin significantly reduced LPS-induced infiltration of inflammatory cells and the production of TNF-α, IL-1β, and IL-6 in the BALF. The activity of MPO and lung wet/dry ratio were also attenuated by amygdalin. Furthermore, the western blotting analysis showed that amygdalin remarkably inhibited LPS-induced NF-κB and NLRP3 activation. These findings indicate that amygdalin has a protective effect on LPS-induced ALI in mice. The mechanism may be related to the inhibition of NF-κB and NLRP3 signaling pathways.     

Protective Effect of Isorhamnetin on Lipopolysaccharide-Induced Acute Lung Injury in Mice

Isorhamnetin has been reported to have anti-inflammatory, anti-oxidative, and anti-proliferative effects. The aim of this study was to investigate the protective effect of isorhamnetin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice by inhibiting the expression of cyclooxygenase-2 (COX-2). The effects of isorhamnetin on LPS-induced lung pathological damage, wet/dry ratios and the total protein level in bronchoalveolar lavage fluid (BALF), inflammatory cytokine release, myeloperoxidase (MPO) and superoxide dismutase (SOD) activities, and malondialdehyde (MDA) level were examined. In addition, the COX-2 activation in lung tissues was detected by Western blot. Isorhamnetin pretreatment improved the mice survival rates. Moreover, isorhamnetin pretreatment significantly attenuated edema and the pathological changes in the lung and inhibited protein extravasation in BALF. Isorhamnetin also significantly decreased the levels of inflammatory cytokines in BALF. In addition, isorhamnetin markedly prevented LPS-induced oxidative stress. Furthermore, isorhamnetin pretreatment significantly suppressed LPS-induced activation of COX-2. Isorhamnetin has been demonstrated to protect mice from LPS-induced ALI by inhibiting the expression of COX-2.     

PI3K/Akt信号通路上调急性肺损伤大鼠肺泡上皮钠通道表达

目的 探讨PI3K/Akt信号通路对急性肺损伤(ALI)大鼠肺泡上皮钠通道(ENaC)α、β和γ亚基表达的影响.方法 成年SD大鼠随机分为对照组、ALI组(脂多糖)、胰岛素组及渥曼青霉素组,每组5只.观察肺组织病理改变,收集支气管肺泡灌洗液(BALF),测量总肺水含量,RT-PCR和Western blot测定ENaC mRNA和蛋白、p-Akt表达.结果 胰岛素组BALF蛋白含量、髓过氧化物酶(MPO)活性、总肺水含量较ALI组显著减少(P＜0.05),渥曼青霉素组BALF蛋白含量、MPO活性及总肺水含量较胰岛素组显著增加(P＜0.05).ALI组α-、β-和γ-ENaC蛋白表达显著低于对照组(0.33 ±0.06 vs 1.27 ±0.07,0.18±0.04 vs 0.72±0.04,0.37±0.04 vs0.69±0.05)(P＜0.05).胰岛素组蛋白表达α-ENaC(2.19 ±0.04)、β-ENaC(1.18 ±0.07)和γ-ENaC(1.18 ±0.08)显著高于ALI组(P＜0.05).渥曼青霉素组蛋白表达α-ENaC(0.86 ±0.09)、β-ENaC (0.58±0.05)和γ-ENaC (0.59±0.02)显著低于胰岛素组(P＜ 0.05).胰岛素组ENaC mRNA和p-Akt较ALI组显著升高(P＜0.05).渥曼青霉素组ENaC mRNA和p-Akt较胰岛素组显著降低(P＜0.05).结论 激活H3K/Akt通路上调3种ENaC亚基表达,从而清除肺水肿液.     

Asiatic Acid Inhibits Lipopolysaccharide-Induced Acute Lung Injury in Mice

Asiatic acid (AA), a major triterpene isolated from Centella asiatica (L.) Urban, is known to exert various pharmacological activities, including anti-inflammatory and antioxidant effects. The aim of this study was to evaluate the anti-inflammatory effects of AA on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and clarify the underlying mechanisms. Lung pathological changes were assessed by H&E staining. The myeloperoxidase (MPO) activity was detected by MPO assay. The levels of inflammatory cytokines were measured by ELISA. TLR4 and NF-kB expression was detected by Western blot analysis. AA obviously inhibited LPS-induced lung histopathological changes, MPO activity, and inflammatory cell numbers in bronchoalveolar lavage fluid (BALF). Treatment of AA also inhibited LPS-induced TNF-α, IL-6, and IL-1β production. Furthermore, Western blot analysis showed that AA inhibited LPS-induced TLR4 expression and NF-kB activation. In conclusion, AA inhibited LPS-induced ALI in mice by inhibiting inflammatory cytokine production, which is mediated via blocking of the TLR4/NF-kB signaling pathway.     

内源性H2S在CCK-8减轻脂多糖所致急性肺损伤中的作用

目的：探讨内源性硫化氢(H₂S)在八肽胆囊收缩素(CCK-8)减轻脂多糖（LPS）所致急性肺损伤(ALI)中的作用。方法: 将84只SD大鼠随机分为正常对照组、LPS组（经气管内滴注LPS复制ALI）、NaHS(H₂S供体)+LPS组、炔丙基甘氨酸［胱硫醚-γ-裂解酶（CSE）抑制剂，PPG］+LPS组、CCK-8+LPS组、PPG+CCK-8+LPS组和CCK- 8组。给药后分别于4 h和8 h处死动物，测定肺湿/干比值；光镜观察肺组织形态学改变；化学法检测血浆H₂S含量，肺组织MDA含量、MPO活性和CSE活性；放免法检测肺组织P-selectin含量；RT-PCR检测肺组织CSE mRNA的表达；并行支气管肺泡灌洗，检测支气管肺泡灌洗液(BALF)中蛋白含量。结果: 气管内滴注LPS可引起肺组织明显的形态学改变；肺湿/干比值、BALF中蛋白含量及肺组织MDA、MPO活性和P-selectin水平增高；血浆H2S含量、肺组织CSE活性及CSE mRNA表达下降。预先给予NaHS或CCK-8可显著减轻LPS所致的上述改变，且血浆H₂S含量、肺组织CSE活性及CSE mRNA表达高于相应的LPS组；预先给予PPG可加重LPS所致的肺损伤，而血浆H₂S含量、肺组织CSE活性及CSE mRNA表达分别低于相应的LPS组和CCK-8+LPS组。结论: CCK-8可通过内源性H₂S介导的抗氧化、抑制PMN黏附聚集等效应发挥减轻LPS所致肺损伤的作用。     

Anti-inflammatory Role of Pilose Antler Peptide in LPS-Induced Lung Injury

The present study was designed to investigate the effects of pilose antler peptide (PAP) on lipopolysaccharide (LPS)-induced lung injury. BalB/c mice intraperitoneally received PAP (10 and 20 mg/kg) or dexamethasone (2 mg/kg) 1 h prior to intratracheal instillation of LPS. PAP significantly decreased lung wet-to-dry weight (W/D) ratio and lung myeloperoxidase (MPO) activity and restored LPS-induced lung histopathological changes. PAP also increased super oxide dismutase (SOD) level and inhibited malondialdehyde (MDA) content and levels of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) in LPS-stimulated mice. Furthermore, we demonstrated that PAP inhibited Rho/NF-κB pathway in LPS-induced mice. Our experimental results indicated that the protective mechanism of PAP might be attributed partly to the inhibition of Rho/NF-κB pathway.     

Artesunate Protects LPS-Induced Acute Lung Injury by Inhibiting TLR4 Expression and Inducing Nrf2 Activation

Artesunate, a derivative of artemisinin, has been reported to have anti-inflammatory property. However, few studies showed the protective effects of artesunate on lung injury. In this study, we aimed to investigate the effects of artesunate on LPS-induced lung injury in mice. The mice were treated with artesunate 1 h before or after LPS treatment. The effects of artesunate on lung MPO activity and malondialdehyde (MDA) content were detected. The lung wet/dry radio and the numbers of inflammatory cells in BALF were also measured. ELISA was used to evaluate the levels of TNF-α, IL-1β, and IL-6 in BALF. Western blot analysis was adapted to detect TLR4 and Nrf2 signaling pathways. The results showed that artesunate protected against LPS-induced ALI by decreasing the numbers of inflammatory cells, lung edema, MPO activity, and MDA content. Furthermore, artesunate significantly inhibited the levels of TNF-α, IL-1β, and IL-6. Artesunate also inhibited LPS-induced IL-6 and IL-8 production in the A549 cells. In addition, artesunate dose-dependently suppressed LPS-induced TLR4 expression and NF-κB activation. The expression of Nrf2 and HO-1 were also up-regulated by artesunate. The data suggest that artesunate possesses anti-inflammatory and anti-oxidant properties against LPS-induced ALI via inhibiting TLR4 signaling pathway and activating Nrf2 signaling pathway.     

Vagal Efferent Fiber Stimulation Ameliorates Pulmonary Microvascular Endothelial Cell Injury by Downregulating Inflammatory Responses

Electrical stimulation of the vagus nerve may have positive effects on many inflammatory diseases. This study determined the beneficial effects of vagus nerve stimulation and the mechanisms by which it attenuates lipopolysaccharide (LPS)-induced acute lung injury (ALI). Rats were intraperitoneally injected with 10 mg/kg LPS to induce ALI. The results showed that vagus nerve stimulation could improve lung injury, as evidenced by remarkable reductions in lung edema (wet-to-dry weight ratio), neutrophil infiltration (myeloperoxidase activity), and pulmonary permeability [total number of cells and protein concentrations in bronchoalveolar lavage fluid (BALF)]. In addition, vagus nerve stimulation not only decreased the expressions of Src-suppressed C kinase substrate and E-selectin proteins in lung tissue but also effectively attenuated the concentrations of the proinflammatory cytokines tumor necrosis factor-α, interleukin-1β, and interleukin-6 in BALF. These suggest that vagus nerve stimulation is a suitable treatment for LPS-induced ALI and indicate that it helps ameliorate pulmonary microvascular endothelial cell injury by downregulating inflammatory responses.