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acute lung injury and ARDS in acute pancreatitis: Mechanisms and potential intervention

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World Journal of Gastroenterology 2010年第17期16卷 2094-2099页

作者： Roland Andersson Department of Surgery Clinical Sciences LundLund University Lund University Hospital SE-221 85 LundSweden

acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in acute pancreatitis still represents a substantial problem,with a mortality rate in the range of 30%-40%.The present review evaluates underlying pathophysiological mechanisms in both ALI and ARDS and potential clinical *** mediators and pathophysiological pathways are involved during the different phases of ALI and *** initial exudative phase is characterized by diffuse alveolar damage,microvascular injury and influx of inflammatory *** phase is followed by a fibro-proliferative phase with lung repair,type Ⅱ pneumocyte hypoplasia and proliferation of *** derived from polymorphonuclear neutrophils,various pro-inflammatory mediators,and phospholipases are all involved,among *** factors that promote pancreatitis-associated ALI may be found in the gut and mesenteric *** is a lack of complete understanding of the underlying mechanisms,and by improving our knowledge,novel tools for prevention and intervention may be developed,thus contributing to improved outcome.

关键词： acute lung injury acute respiratory distress syndrome acute pancreatitis Etiology Pathophysiology

Review:acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism,present strategies and future perspectives of therapies

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2007年第1期8卷 60-69页

作者： LUH Shi-ping CHIANG Chi-huei Department of Surgery Chung-Shan Medical University Hospital 402 Taichung Taiwan China Division of Pulmonary Immunology and Infectious Diseases Taipei Veterans General Hospital 112 Taipei Taiwan China

acute lung injury/acute respiratory distress syndrome （ALI/ARDS）, which manifests as non-cardiogcnic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.

关键词： acute lung injury acute respiratory distress syndrome Ventilator Cell therapy

Piezo1-targeted aerosol inhalation nanoparticles for acute lung injury

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Journal of Materials Science & Technology 2023年第10期141卷 21-31页

作者： Xinxin Liu Xuwei Ling Jiachen He Xingzhi Liu Lin Wang Huiling Liu Chang Liu Yi Wang Xiao Lin Chunhua Ling Qin Shi Department of Respiratory Medicine the First Affiliated Hospital of Soochow UniversitySuzhou 215031China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Gannan Medical University/Gannan Branch of National Clinical Research Center for GeriatricsGanzhou 341000China Department of Orthopedics the First Affiliated Hospital of Soochow UniversityOrthopedic Institute of Soochow UniversitySuzhou 215031China School of Nano-Tech and Nano-Bionics University of Science and Technology of ChinaSuzhou 215123China University of Science and Technology of China Hefei 230026China National Clinical Research Center for Hematologic Diseases the First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215031China

Inhaled drug-containing nanocarriers have been well applied as an important strategy in pulmonary *** lung injury(ALI)is characterized by abnormal lung tension and complex pathogenesis,with high mortality because of the limitations of targeted ***,in the present study,we first identified that the mechanosensitive ion channel Piezo1 participated in the ALI-associated processes induced by lipopolysaccharide(LPS)in vitro and in ***,chitosan-stabilized bovine serum albu-min nanoparticles(NCs)emulsified with the Piezo1 inhibitor GsMTx4(NC-GsMTx4)were generated and exhibited excellent biocompatibility and biological *** aerosol inhalation,NC-GsMTx4 im-proved lung injury and inhibited cell apoptosis in LPS-stressed ALI mice and alleviated pulmonary fibrosis during the later stage of ***,GsMTx4 could regulate inflammation and apoptosis in lung epithelial cells via NF-κB and ERK1/2 *** summary,our findings provide new insights into the pathological mechanisms of Piezo1 in ALI progression,and nebulized inhalation of NC-GsMTx4 offers a prospective platform for targeting Piezo1 to treat ALI efficiently and conveniently.

关键词： acute lung injury Piezo1 Nanoparticle carrier NF-κB ERK1/2 GsMTx4

Emodin attenuates severe acute pancreatitis-associated acute lung injury by suppressing pancreatic exosome-mediated alveolar macrophage activation

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Acta Pharmaceutica Sinica B 2022年第10期12卷 3986-4003页

作者： Qian Hu Jiaqi Yao Xiajia Wu Juan Li Guixiang Li Wenfu Tang Jingping Liu Meihua Wan Department of Integrated Traditional Chinese and Western Medicine National Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengdu 610041China NHC Key Laboratory of Transplant Engineering and Immunology Frontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041China

Severe acute pancreatitis-associated acute lung injury(SAP-ALI) is a serious disease associated with high mortality. Emodin has been applied to alleviate SAP-ALI;however, the mechanism remains unclear. We report that the therapeutic role of emodin in attenuating SAP-ALI is partly dependent on an exosomal mechanism. SAP rats had increased levels of plasma exosomes with altered protein contents compared to the sham rats. These infused plasma exosomes tended to accumulate in the lungs and promoted the hyper-activation of alveolar macrophages and inflammatory damage. Conversely,emodin treatment decreased the plasma/pancreatic exosome levels in the SAP rats. Emodin-primed exosomes showed less pro-inflammatory effects in alveolar macrophages and lung tissues than SAP exosomes. In detail, emodin-primed exosomes suppressed the NF-κB pathway to reduce the activation of alveolar macrophage and ameliorate lung inflammation by regulating PPARγ pathway, while these effects were amplified/abolished by PPARγ agonist/antagonist. Blockage of pancreatic acinar cell exosome biogenesis also exhibited suppression of alveolar macrophage activation and reduction of lung inflammation. This study suggests a vital role of exosomes in participating inflammation-associated organ-injury,and indicates emodin can attenuate SAP-ALI by reducing the pancreatic exosome-mediated alveolar macrophage activation.

关键词： Severe acute pancreatitis acute lung injury Emodin Exosome Macrophages Lisocitrate dehydrogenase 1 Peroxisome proliferatoractivated receptorγ Nuclear factor kB

Baicalin inhibits inflammation of lipopolysaccharide-induced acute lung injury via toll like receptor-4/myeloid differentiation primary response 88/nuclear factor-kappa B signaling pathway

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Journal of Traditional Chinese Medicine 2022年第2期42卷 200-212页

作者： ZHU Changle FENG Cuiling FENG Feng Yao Xiaoqin WANG Guishu SHI Liangtian ZHENG Jiakun Department of respiration Dongzhimen Hospital Affiliated to Beijing University of Chinese MedicineBeijing 100000China Department of traditional Chinese Medicine Peking University People's HospitalBeijing100000China Department of Traditional Chinese Medicine Peking University International HospitalBeijing 100000China

OBJECTIVE:To explore the effect and mechanism of baicalin in the treatment of acute lung injury(ALI)by in vivo and in vitro ***:ALI was induced by instilling 10 mg/m L lipopolysaccharide(LPS)into the airway of *** doses of baicalin(50 and 100 mg·kg^(-1)·d^(-1 ))were administered by gavage one day before ***:Baicalin significantly reduced the permeability of the alveolocapillary membrane,alleviated tissue injury and inflammatory infiltration,and inhibited the secretion of inflammatory factors and the infiltration of *** decline in these inflammations was related to the inhibition of the toll like receptor-4(TLR4)/myeloid differentiation factor 88(My D88)/nuclear factor-kappa B(NF-κB)/nod-like receptor pyrin containing 3(NLRP3)signaling pathway and the mitogen-activated protein kinase(MAPK)signaling ***:Baicalin inhibits the secretion of inflammatory factors by inhibiting the TLR4-My D88-NF-κB/NLRP3 pathway and the MAPK signaling ***,it reduces lung bronchial epithelial layer,alveolar damage,and pulmonary edema as detected in the in vivo and in vitro ***,baicalin may be a potential preventive and therapeutic drug for ALI.

关键词： baicalin acute lung injury epithelial cells lipopolysaccharides inflammation

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Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway

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Chinese Journal of Natural Medicines 2023年第6期21卷 423-435页

作者： WANG Shuhui LEI Pan FENG Ying JIANG Mingzhu LIU Zegan SHEN Ting MA Shinan WANG Libo GUO Xingrong DU Shiming 无 School of Pharmaceutical Sciences Hubei Key Laboratory of Wudang Local Chinese Medicine ResearchTaihe HospitalHubei University of MedicineShiyan 442000China Department of Neurosurgery Hubei Key Laboratory of Embryonic Stem Cell ResearchTaihe HospitalHubei University of MedicineShiyan 442000China Hubei provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem Cells Taihe HospitalHubei University of MedicineShiyan 442000HubeiChina Hubei Hongshan Laboratory College of Biomedicine and HealthHuazhong Agricultural UniversityWuhan 430070China

acute lung injury(ALI)is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers,resulting in high incidence and mortality ***,there is a lack of safe and effective drugs for the treatment of *** a previous clinical study,we observed that Jinyinqingre oral liquid(JYQR),a Traditional Chinese Medicine formulation prepared by the Taihe Hospital,Affiliated Hospital of Hubei University of Medicine,exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical ***,the potential role of JYQR in ALI/acute respiratory distress syndrome(ARDS)and its anti-inflammatory mechanism remains ***,the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide(LPS)-induced ALI and an in vitro RAW264.7 cell *** yielded substantial improvements in LPS-induced histological alterations in lung ***,JYQR administration led to a noteworthy reduction in total protein levels within the BALF,a decrease in MPAP,and attenuation of pleural *** findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced *** investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins,namely NLRP3 and GSDMD,as well as proinflammatory cytokine levels in mice and RAW2647 ***,JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD *** exerts a protective effect against LPS-induced ALI in mice,and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

关键词： Jinyinqingre oral liquid acute lung injury Lipopolysaccharide Inflammation NF-κB/NLRP3/GSDMD pathway

Protective Effects of Danmu Extract Syrup on acute lung injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair

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Chinese Journal of Integrative Medicine 2024年第3期30卷 243-250页

作者： XU Han XU Si-cong LI Li-yan WU Yu-huang TAN Yin-feng CHEN Long LIU Pei LIANG Chang-fu HE Xiao-ning LI Yong-hui Hainan Provincial Key Lab of Research&Development on Tropic Herbs Hainan Medical UniversityHaikou571199China Department of Stomatology the Second Affiliated Hospital of Hainan Medical UniversityHaikou571199China

Objective:To investigate the effects of Danmu Extract Syrup(DMS) on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice and explore the ***:Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table(n=12),including control(normal saline),LPS(5 mg/kg),LPS+DMS 2.5 mL/kg,LPS+DMS 5 mL/kg,LPS+DMS 10 mL/kg,and LPS+Dexamethasone(DXM,5 mg/kg) *** pretreatment with DMS and DXM,the ALI mice model was induced by LPS,and the bronchoalveolar lavage fluid(BALF) were collected to determine protein concentration,cell counts and inflammatory *** lung tissues of mice were stained with hematoxylin-eosin,and the wet/dry weight ratio(W/D) of lung tissue was *** levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-1βin BALF of mice were detected by enzyme linked immunosorbent *** expression levels of Claudin-5,vascular endothelial(VE)-cadherin,vascular endothelial growth factor(VEGF),phospho-protein kinase B(p-Akt) and Akt were detected by Western blot ***:DMS pre-treatment significantly ameliorated lung histopathological *** with the LPS group,the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment(Plung injury.

关键词： Danmu Extract Syrup acute lung injury inflammatory factors vascular endothelial growth factor phosphoinositide 3-kinase/protein kinase B Chinese medicine Nauclea officinalis

Beneficial effects of Houttuynia cordata polysaccharides on “two-hit” acute lung injury and endotoxic fever in rats associated with anti-complementary activities

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Acta Pharmaceutica Sinica B 2018年第2期8卷 218-227页

作者： Yan Lu Yun Jiang Lijun Ling Yunyi Zhang Hong Li Daofeng Chen Department of Pharmacognosy School of Pharmacy Fudan University Department of Pharmacology School of Pharmacy Fudan University

Houttuynia cordata Thunb. is a traditional herb used for clearing heat and eliminating toxins,and has also been used for the treatment of severe acute respiratory syndrome(SARS). In vitro, the crude H. cordata polysaccharides(CHCP) exhibited potent anti-complementary activity through both the classical and alternative pathways by acting on components C3 and C4 of the complement system without interfering with the coagulation system. This study was to investigate the preventive effects of CHCP on acute lung injury(ALI) induced by hemorrhagic shock plus lipopolysaccharide(LPS) instillation(two-hit)and LPS-induced fever in rats. CHCP significantly attenuated pulmonary injury in the "two-hit" ALI model by reducing pulmonary edema and protein exudation in bronchoalveolar lavage fluid(BALF). In addition, it reduced the deposit of complement activation products in the lung and improved oxidantantioxidant imbalance. Moreover, CHCP administration inhibited fever in rats, reduced the number of leukocytes and restored serum complement levels. The inhibition on the inappropriate activation of complement system by CHCP may play an important role in its beneficial effects on inflammatory diseases. The anti-complementary polysaccharides are likely to be among the key substances for the heatclearing function of H. cordata.

关键词： Houttuynia cordata Polysaccharides Fever acute lung injury Anti-complementary

Yemazhui(Herba Eupatorii Lindleyani)ameliorates lipopolysaccharide-induced acute lung injury via modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flor

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Journal of Traditional Chinese Medicine 2024年第2期44卷 303-314页

作者： REN Li HAI Yang YANG Xue LUO Xianqin Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases College of Traditional Chinese MedicineChongqing Medical UniversityChongqing 400016China College of Basic Medicine Chongqing Medical UniversityChongqing 400016China

OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in ***:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry ***,HEL was found to suppress LPS-induced ALI in ***-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)*** model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI *** counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and ***,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal ***:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora *** study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung *** addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturban

关键词： Yemazhui(Herba Eupatorii Lindleyani) acute lung injury anti-inflammation toll-like receptor 4 nuclear factor kappa-B nod-like receptor family pyrin domain-containing 3 protein signal transduction gastrointestinal microbiome