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Therapeutic effects of Caspase-1 inhibitors on acute lung injury in experimental severe acute pancreatitis

World Journal of Gastroenterology 2007年第4期13卷 623-627页

作者： Xiao-Hua Zhang Ren-Min Zhu Wen-An Xu Hai-Jun Wan Heng Lu Department of Gastroenterology Jinling Hospital Nanjing 210002 Jiangsu Province China

AIM： To assess the therapeutic effect of Caspase-1 inhibitors （ICE-I） on acute lung injury （ALI） in experimental severe acute pancreatitis （SAP）. METHODS： Forty-two SD rats were randomly divided into 3 groups： healthy controls （HC, n = 6）; SAP-S group （n = 18）; SAP-ICE-i group （n = 18）. SAP was induced by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct. HC rats underwent the same surgical procedures and duct cannulation without sodium taurocholate infusion, in SAP-S group, rats received the first intraperitoneal injection of isotonic saline 2 h after induction of acute pancreatitis and a repeated injection after 12 h. In SAP-ICE-I group, the rats were firstly given ICE inhibitors intraperitoneally 2 h after induction of pancreatitis. As in SAP-S group, the injection was repeated at 12 h. Serum 1L-1β was measured by EUSA. Intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were detected by semi-quantitative RT-PCR. The wet/dry weight ratios and histopathological changes of the lungs were also evaluated. RESULTS： Serum IL-1β levels in SAP-S group were 276.77 ± 44.92 pg/mL at 6 h, 308.99 ± 34.95 pg/mL at 12 h, and 311.60 ± 46.51 pg/mL at 18 h, which were increased significantly （P 〈 0.01, vs HC）. in SAP- ICE-I group, those values were decreased significantly （P 〈 0.01, vs SAP-S）. intrapulmonary expression of Caspase-1, IL-1β and IL-18 mRNA were observed in the HC group, while they were increased significantly in the SAP-S group （P 〈 0.01, vs HC）. The expression of IL-lβ and IL-18 mRNA were decreased significantly in the SAP- ICE-I group （P 〈 0.01, vs SAP-S）, whereas Caspase-1 mRNA expression had no significant difference （P 〉 0.05）. The wet/dry weight ratios of the lungs in the SAP-S group were increased significantly （P 〈 0.05 at 6 h, P 〈 0.01 at 12 h and 18 h, vs HC） and they were decreased significantly in the SAP-ICE-I group （P 〈 0.05, vs SAP-S）.Caspase-1 inhibitors ameliorated the severity of ALl in SAP.CONCLUSION： Caspas

关键词： severe acute pancreatitis Caspase-1 Interleukin-lβ Interleukin-18 acute lung injury

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Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis

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World Journal of Gastroenterology 2005年第43期11卷 6770-6774页

作者： Cheng Zhang Chun-Lin Ge Ren-Xuan Guo San-Guang He Department of General Surgery No. 1 Hospital of China Medical University Shenyang 110001 Liaoning Province China

AIM： To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis （SAP）. METHODS： SAP model of rats was established by retrograde injection of 5% sodium taurocholate （1 mL/kg） into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators： decay accelerating factor （DAF; CD55）, 20 ku homologous restriction factor （HRF20; CD59） and membrane cofactor protein （MCP; CEH6）, in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A （n = 21） received no treatment after the SAP model was established; group B （n = 20） was given IL-4 （8 IJg/animal） intraperitoneally 0.5 h before the SAP model was established; group C （n = 20） was given IL-4 （8 μg/animal） intraperitoneaUy 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model. RESULTS： Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced. A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis （r = -0.748, -0.827, -0.723; P〈0.01）. In the second series of experiments, no matter when the treatment of IL-4 was given （before or after the induction of SAP model）, the serum level of amylase or lipase was decreased

关键词： severe acute pancreatitis Complement activation regulators Interleukin-4

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Intra-abdominal pressure monitoring in predicting outcome of patients with severe acute pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2007年第4期6卷 420-423页

作者： Zhang, Wei-Fang Ni, Yun-Lan Cai, Ling Li, Tong Fang, Xue-Ling Zhang, Yun-Tao Zhejiang Univ Sch Med Affiliated Hosp 1 Intens Care Unit Hangzhou 310003 Peoples R China Hangzhou Hosp Tradit Chinese Med Dept Resp Syst Hangzhou 310003 Peoples R China

BACKGROUND: severe acute pancreatitis (SAP) is a serious disease with many complications, high mortality and poor prognosis. It is characterized by rapid deterioration and poses one of the most difficult challenges in clinical practice. Previous investigations suggest that SAP is one of the main causes of intra-abdominal pressure (IAP) increase. The aim of this study was to evaluate the utility of IAP-monitoring in predicting the severity and prognosis of SAP. METHODS: Eighty-nine patients with SAP who had been treated from February 2001 to December 2005 were studied. Since bladder pressure accurately reflects IAP, we measured it instead of IAP. Bladder pressure was measured at the time of admission and every 12 hours in the course of the disease, 9 consecutive times in all. The APACHE II scores of all patients were obtained within 24 hours after admission. According to a maximum bladder pressure severely-elevated. Mortality and mean APACHE II scores in the two groups were calculated. In addition, the mean bladder pressure and APACHE II scores in survivors were compared with those in deaths. RESULTS: Sixty-eight of the 89 patients were in the severely-elevated group. Mortality and mean APACHE II scores in this group were much higher than those in the mildly-elevated group (mortality, 39.71% vs. 9.52%; mean APACHE II score, 23.15 +/- 7.42 vs. 15.95 +/- 5.35, P<0.01). The mean bladder pressures and APACHE II scores in deaths were significantly greater than those in survivors (mean bladder pressure, 14.1 +/- 3.8 vs. 9.2 +/- 2.3 cmH(2)O, P<0.01; mean APACHE II score, 27.83 +/- 4.87 vs. 18.37 +/- 6.74, P<0.01). CONCLUSION: It is suggested that IAP may be used as a marker of the severity and prognosis of SAP.

关键词： severe acute pancreatitis intra-abdominal pressure APACHE II score mortality

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Protective effects of Ligustrazine,Kakonein and Panax Notoginsenoside on the small intestine and immune organs of rats with severe acute pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2011年第6期10卷 632-637页

作者： Xi-Ping Zhang,Jun Jiang,Qi-Hui Cheng,Qian Ye,Wei-Juan Li,Hua Zhu and Jun-Ya Shen Department of General Surgery,Department of Gynecology and Obstetrics and Central Laboratory Department,Hangzhou First People’s Hospital,Hangzhou 310006,China Zhejiang Chinese Medical University,Hangzhou 310053,China Department of General Surgery Hangzhou First People's Hospital Hangzhou 310006 China Zhejiang Chinese Medical University Hangzhou 310053 China Department of Gynecology and Obstetrics Hangzhou First People's Hospital Hangzhou 310006 China Central Laboratory Department Hangzhou First People's Hospital Hangzhou 310006 China

BACKGROUND:severe acute pancreatitis (SAP) is characterized by fatal pathogenic conditions and a high *** is important to study SAP complicated with multiple organ *** this study we compared the protective effects of three traditional Chinese medicines (Ligustrazine,Kakonein and Panax Notoginsenoside) on the small intestine and immune organs (thymus,spleen and lymph nodes) of rats with SAP and explored their mechanism of ***:One hundred forty-four rats with SAP were randomly divided into model control,Ligustrazine-treated,Kakonein-treated,and Panax Notoginsenoside-treated groups (n=36 per group).Another 36 normal rats comprised the sham-operated *** to the different time points after operation,the experimental rats in each group were subdivided into 3-,6-and 12-hour subgroups (n=12).At various time points after operation,the mortality rate of rats and pathological changes in the small intestine and immune organs were recorded and the serum amylase levels were ***:Compared to the model control groups,the mortality rates in all treated groups declined and the pathological changes in the small intestine and immune tissues were relieved to different *** serum amylase levels in the three treated groups were significantly lower than those in the model control group at 12 *** pathological severity scores for the small intestinal mucosa,thymus and spleen (at 3 and 12 hours) in the Ligustrazine-treated group,for the thymus (at 3 and 12 hours) and spleen (at 3 and 6 hours) in the Kakonein-treated group,and for the thymus (at 3 hours)and spleen (at 3 hours) in the Panax Notoginsenoside-treated group were significantly lower than those in the model control *** pathological severity scores of the small intestinal mucosa (at 6 and 12 hours) and thymus (at 6 hours) in the Ligustrazine-treated group were significantly lower than those in the Kakonein-and Panax Notoginsenoside-treated ***:All the t

关键词： severe acute pancreatitis traditional Chinese medicine small intestine multiple organs apoptosis

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Genome-wide map of N6-methyladenosine circular RNAs identified in mice model of severe acute pancreatitis

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World Journal of Gastroenterology 2021年第43期27卷 7530-7545页

作者： Jun Wu Xiao-Hui Yuan Wen Jiang Yi-Chen Lu Qi-Lin Huang Yi Yang Hua-Ji Qie Jiang-Tao Liu Hong-Yu Sun Li-Jun Tang Department of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province The General Hospital of Western Theater CommandChengdu 610036Sichuan ProvinceChina College of Medicine Southwest Jiaotong UniversityChengdu 610036Sichuan ProvinceChina Laboratory of Basic Medicine The General Hospital of Western Theater CommandChengdu 610036Sichuan ProvinceChina

BACKGROUND severe acute pancreatitis(SAP)is a deadly inflammatory disease with complex pathogenesis and lack of effective therapeutic options.N6-methyladenosine(m6A)modification of circRNAs plays important roles in physiological and pathological ***,the roles of m6A circRNA in the pathological process of SAP remains *** To identify transcriptome-wide map of m6A circRNAs and to determine their biological significance and potential mechanisms in *** The SAP in C57BL/6 mice was induced using 4%sodium taurocholate *** transcriptome-wide map of m6A circRNAs was identified by m6A-modified RNA immunoprecipitation *** biological significance of circRNAs with differentially expressed m6A peaks was evaluated through gene ontology and Kyoto Encyclopedia of Genes and Genomes *** underlying mechanism of m6A circRNAs in SAP was analyzed by constructing of m6A circRNAmicroRNA *** expression of demethylases was determined by quantitative polymerase chain reaction and western blot to deduce the possible mechanism of reversible m6A process in *** Fifty-seven circRNAs with differentially expressed m6A peaks were identified by m6A-modified RNA immunoprecipitation sequencing,of which 32 were upregulated and 25 *** analysis of these m6A circRNAs in SAP found some important pathways involved in the pathogenesis of SAP,such as regulation of autophagy and protein *** m6A circRNA–miRNA networks,several important miRNAs participated in the occurrence and progression of SAP were found to bind to these m6A circRNAs,such as miR-24-3p,miR-26a,miR-92b,miR-216b,miR-324-5p and ***,the total m6A level of circRNAs was reduced,while the demethylase alkylation repair homolog 5 was upregulated in *** m6A modification of circRNAs may be involved in the pathogenesis of *** findings may provide novel insights to explore the possible pathogenetic mechanism of SAP and seek new poten

关键词： severe acute pancreatitis Circular RNAs N6-methyladenosine MeRIP-seq Epigenetic analysis

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Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reduced serum high mobility group box 1 levels in rats

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World Journal of Gastroenterology 2008年第28期14卷 4546-4550页

作者： Zhi-Yong Yang Yan Ling Tao Yin Jing Tao Jiong-Xin Xiong He-Shui Wu Chun-You Wang Department of Pancreatic Surgery Xiehe Hospital Tongji Medical College Huazhong University of Sciecne and Technology Wuhan 430022 Hubei Province China

AIM： To investigate the effect of delayed ethyl pyruvate （EP） delivery on distant organ injury, survival time and serum high mobility group box 1 （HMGB1） levels in rats with experimental severe acute pancreatitis （SAP）. METHODS： A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups （n = 32 in each group）： sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP （30 mg/kg） at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate arninotransferase （AST）, alanine arninotransferase （ALT）, blood urea nitrogen （BUN）, and creatinine （Cr） levels were measured. Lung wet-to-dry-weight （W/D） ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. RESULTS： Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios （8.22 ±0.42 vs 9.76 ± 0.45, P 〈 0.01）, pulmonary histological scores （7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01）, serum AST （667 ± 103 vs 1 368 ± 271, P 〈 0.01）, ALT （446 ± 91 vs 653 ± 98, P 〈 0.01） and Cr （1.2 ± 0.3 vs 1.8 ± 0.3, P 〈 0.01） levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h （P 〈 0.01）. CONCLUSION： Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome （MODS） in SAP patients.

关键词： severe acute pancreatitis Ethyl pyruvate High mobility group box 1 multiple organ dysfunction syndrome Survival time

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Circulating miRNAs as biomarkers for severe acute pancreatitis associated with acute lung injury

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World Journal of Gastroenterology 2017年第41期23卷 7440-7449页

作者： Xiao-Guang Lu Xin Kang Li-Bin Zhan Li-Min Kang Zhi-Wei Fan Li-Zhi Bai Depart-ment of Emergency Zhongshan Hospital Dalian University College of Basic Medicine Nanjing University of Chinese Medicine Department of Hepatobiliary and Pancreatic Surgery Puer People's Hospital

AIM To identify circulating micro(mi)RNAs as biological markers for prediction of severe acute pancreatitis(SAP) with acute lung injury(ALI).METHODS Twenty-four serum samples were respectively collected and classified as SAP associated with ALI and SAP without ALI, and the mi RNA expression profiles were determined by microarray analysis. These mi RNAs were validated by quantitative reverse transcriptionpolymerase chain reaction, and their putative targets were predicted by the online software Target Scan, mi Randa and Pic Tar database. Gene ontology(GO) and Kyoto encyclopedia of genes and genomes(commonly known as KEGG) were used to predict their possible functions and pathways *** We investigated 287 mi RNAs based on microarray data analysis. Twelve mi RNAs were differentially expressed in the patients with SAP with ALI and those with SAP without ALI. Hsa-mi R-1260 b, 762, 22-3 p, 23 b and 23 a were differently up-regulated and hsa-mi R-550 a*, 324-5 p, 484, 331-3 p, 140-3 p, 342-3 p and 150 were differently down-regulated in patients with SAP with ALI compared to those with SAP without ALI. In addition, 85 putative target genes of the significantly dysregulated mi RNAs were found by Target Scan, mi Randa and Pic Tar. Finally, GO and pathway network analysis showed that they were mainly enriched in signal transduction, metabolic processes, cytoplasm and cell *** This is the first study to identify 12 circulating mi RNAs in patients with SAP with ALI, which may be biomarkers for prediction of ALI after SAP.

关键词： miRNAs severe acute pancreatitis acute lung injury Biomarker Microarray analysis

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Effects of ω-3 fatty acids on toll-like receptor 4 and nuclear factor-κB p56 in lungs of rats with severe acute pancreatitis

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World Journal of Gastroenterology 2016年第44期22卷 9784-9793页

作者： Bin Wang Xiao-Wei Wu Mei-Xia Guo Min-Li Li Xiao-Bing Xu Xin-Xin Jin Xiao-Hua Zhang Department of Gastroenterology Jinling Hospital

AIM To determine the effects of ω-3 fatty acids(ω-3FA) on the toll-like receptor 4(TLR4)/nuclear factor κB p56(NF-κBp56) signal pathway in the lungs of rats with severe acute pancreatitis(SAP).METHODS A total of 56 Sprague-Dawley rats were randomly divided into 4 groups: control group, SAP-saline group, SAP-soybean oil group and SAP-ω-3FA group. SAP was induced by the retrograde infusion of sodium taurocholate into the pancreatic duct. The expression of TLR4 and NF-κBp56 in the lungs was evaluated by immunohistochemistry and Western blot analysis. The levels of inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha in the lungs were measured by enzyme-linked immunosorbent assay. RESULTS The expression of TLR4 and NF-κBp56 in lungs and of inflammatory cytokines in serum significantly increased in the SAP group compared with the control group(P < 0.05), but was significantly decreased in the ω-3FA group compared with the soybean oil group at 12 and 24 h(P < 0.05).CONCLUSION During the initial stage of SAP, ω-3FA can efficiently lower the inflammatory response and reduce lung injury by triggering the TLR4/NF-κBp56 signal pathway.

关键词： severe acute pancreatitis ω-3 fatty acids Lung injury Toll-like receptor 4 Nuclear factor-κB p56 Cytokine

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Clinical features and outcomes of patients with severe acute pancreatitis complicated with gangrenous cholecystitis

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Hepatobiliary & Pancreatic Diseases International 2013年第3期12卷 317-323页

作者： Er-Zhen Chen Jie Huang Zhi-Wei Xu Jian Fei En-Qiang Mao Sheng-Dao Zhang Emergency Intensive Care Unit Ruijin Hospital School of Medicine Shanghai Jiaotong University Surgical Intensive Care Unit Ruijin Hospital School of Medicine Shanghai Jiaotong University

BACKGROUND: The effects of gangrenous cholecystitis (GC) and consequent surgical interventions on the clinical outcomes and prognosis of patients with severe acute pancreatitis are not clear. The present study was to characterize the clinical outcomes of patients with severe acute pancreatitis complicated with GC. METHODS: We retrospectively analyzed 253 consecutive patients hospitalized for acute pancreatitis in intensive care unit. Among them, 68 were diagnosed as having severe acute pancreatitis; 10 out of the 68 patients had GC. We compared these 10 patients with GC and 58 patients without GC. The indices analyzed included sepsis/septic shock, pancreatic encephalopathy, acute respiratory distress syndrome, acute renal failure, multiple organ dysfunction syndrome, and death. RESULTS: Specific CT images of GC in patients with severe acute pancreatitis included enlarged and high-tensioned gallbladder, wall thickening, lumenal emphysema, discontinuous and/or irregular enhancement of mucosa, and pericholecystic effusion. The rates of severe sepsis/septic shock (70.0% vs 24.1%, Pacute respiratory distress syndrome (90.0% vs 41.4%, Pacute renal failure (40.0% vs 27.6%, Psevere acute pancreatitis; early diagnosis and intervention for patients with GC can reduce morbidity and mortality.

关键词： severe acute pancreatitis gangrenous cholecystitis surgical intervention

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Medical imaging for pancreatic diseases:Prediction of severe acute pancreatitis complicated with acute respiratory distress syndrome

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World Journal of Gastroenterology 2022年第44期28卷 6206-6212页

作者： Ling-Ji Song Bo Xiao Department of Radiology Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina

In this editorial we comment on the article published in the recent issue of the World Journal of Gastroenterology[2022;28(19):2123-2136].We pay attention to how to construct a simpler and more reliable new clinical predictive model to early identify patients at high risk of acute respiratory distress syndrome(ARDS)associated with severe acute pancreatitis(SAP),and to early predict the severity of organ failure from chest computed tomography(CT)findings in SAP *** we all know,SAP has a sudden onset,is a rapidly changing condition,and can be complicated with ARDS and even multiple organ dysfunction syndrome,and its mortality rate has remained *** present,there are many clinical scoring systems for AP,including the bedside index for severity in AP,acute physiology and chronic health evaluation II,systemic inflammatory response syndrome,Japanese severe score,quick sepsis-related organ failure assessment,***,some of these scoring systems are complex and require multiple and difficult clinical parameters for risk *** the aforementioned biomarkers are readily available,their ability to predict ARDS ***,it is extremely necessary to establish a simple and valuable novel model to predict the development of ARDS in *** addition,the extra-pancreatic manifestations of AP patients often involve the chest,among which pleural effusion and pulmonary consolidation are the more common ***,by measuring the semi-quantitative indexes of chest CT in AP patients,such as the amount of pleural effusion and the number of lobes involved as pulmonary consolidation,it has important reference value for the early diagnosis of SAP complicated with ARDS and is expected to provide a basis for the early treatment of ARDS.

关键词： severe acute pancreatitis acute respiratory distress syndrome Clinical scoring system Prediction model Semi-quantitative

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