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1.
Mol Genet Genomic Med ; : e1048, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31962008

RESUMO

BACKGROUND: Acute pancreatitis in pregnancy (APIP) is a life-threatening disease for both mother and fetus. To date, only three patients with recurrent hypertriglyceridemia-induced APIP (HTG-APIP) have been reported to carry rare variants in the lipoprotein lipase (LPL) gene, which encodes the key enzyme responsible for triglyceride (TG) metabolism. Coincidently, all three patients harbored LPL variants on both alleles and presented with complete or severe LPL deficiency. METHODS: The entire coding regions and splice junctions of LPL and four other TG metabolism genes (APOC2, APOA5, GPIHBP1, and LMF1) were analyzed by Sanger sequencing in a Han Chinese patient who had experienced two episodes of HTG-APIP. The impact of a novel LPL missense variant on LPL protein expression and activity was analyzed by transient expression in HEK293T cells. RESULTS: A novel heterozygous LPL missense variant, p.His210Leu (c.629A > T), was identified in our patient. This variant did not affect protein synthesis but significantly impaired LPL secretion and completely abolished the enzymatic activity of the mutant protein. CONCLUSION: This report describes the first identification and functional characterization of a heterozygous variant in the LPL that predisposed to recurrent HTG-APIP. Our findings confirm a major genetic contribution to the etiology of individual predisposition to HTG-APIP.

2.
Mol Med Rep ; 21(3): 981-988, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31922216

RESUMO

Chemerin is a novel adipokine that regulates immune responses, adipocyte differentiation, and glucose metabolism. However, the role of chemerin in pancreatogenic diabetes mellitus (PDM) remains unknown. PDM is recognized as DM occurring secondary to chronic pancreatitis or pancreatic resection due to the loss of the loss of islet cell mass. The aim of the present study was to investigate the role of chemerin in PDM by collecting blooding samples from DM patients and establishing in vivo PDM model. The present study demonstrated that chemerin levels are decreased in the serum of patients with PDM and are negatively associated with the insulin resistance (IR) status. Chemerin levels also decreased during the development of PDM in C57BL/6 mice, together with increasing serum levels of interleukin­1 and tumor necrosis factor­α and decreasing mRNA expression levels of glucose transporter 2 (GLUT2) and pancreatic and duodenal homeobox 1 (PDX1). Treatment of PDM model mice with chemerin chemokine­like receptor 1 (CMKLR1) agonist, chemerin­9, elevated the serum levels of chemerin and mRNA expression levels of GLUT2 and PDX1, leading to the alleviation of glucose intolerance and IR in these animals. Together, the accumulated data indicated that chemerin may exert a protective function in PDM, perhaps by regulating perhaps by regulating GLUT2 and PDX1 expression, and that the restoration of the chemerin/CMKLR1 pathway may represent a novel therapeutic strategy for PDM.

3.
Gastroenterol Res Pract ; 2019: 6069179, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354807

RESUMO

Objective: To describe the management and prognosis of splenic abscess after splenic arterial embolization in severe acute pancreatitis (SAP) patients. Methods: This is a retrospective observational study. From August 2012 to August 2017, SAP patients with infected pancreatic necrosis (IPN) who underwent splenic arterial embolization after massive hemorrhage of the splenic artery were screened and those who developed splenic abscess were included for analysis. The demographic characteristics, etiology, treatment of splenic abscess, and clinical outcomes of these cases were collected and analyzed. Results: A total of 18 patients with splenic abscess formed after splenic arterial embolization were included for data analysis. The median age of the 18 patients was 46 years. The etiologies included biliary AP, hypertriglyceridemic AP (HTG-AP), and other causes. Ten patients underwent minimally invasive percutaneous drainage only for splenic abscess while the other eight patients received splenectomy. One patient died due to uncontrolled infection and another patient died due to massive bleeding, and the remaining sixteen patients survived. Conclusion: The incidence of splenic abscess was high in patients requiring splenic arterial embolization due to massive bleeding. Our data showed that most splenic abscess could be successfully managed with minimally invasive interventions, and traditional splenectomy should serve as a backup treatment.

5.
Biochem Biophys Res Commun ; 512(4): 670-677, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-30922566

RESUMO

Acute pancreatitis (AP) is one of the most common digestive tract diseases, but effective drug therapy is still lack. Regenerating gene protein 3α (Reg3α) administration significantly reduced the severity of AP in mice. HTD4010 is a new 15 amino acid long synthetic peptide and its biological activities are similar to Reg3α. This study aimed to explore whether HTD4010 could protect pancreatic acinar cells against necrosis and decrease the inflammatory response in AP, and thus to explore underlying mechanisms. It was shown that administration of HTD4010 alleviated significantly the severity of biliary AP (BAP), characterized as less degree of pancreatic histological damage and acinar cell injury (both apoptosis and necroptosis), lower levels of serum amylase and pro-inflammatory cytokines. Moreover, HTD4010 down-regulated the expression of toll-like receptor 4 (TLR4) protein, and TLR4 deficiency eliminated the protective effect of HTD4010 on BAP in mice. In conclusion, these results showed that HTD4010 could alleviate the severity of pancreatitis, reduce the acinar cells necrosis and inflammatory response possibly by TLR4 signaling pathway in AP.

6.
Lipids Health Dis ; 18(1): 68, 2019 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-30885219

RESUMO

BACKGROUND: Hypertriglyceridemia (HTG) is one of the most common etiologies of acute pancreatitis (AP). Variants in five genes involved in the regulation of plasma lipid metabolism, namely LPL, APOA5, APOC2, GPIHBP1 and LMF1, have been frequently reported to cause or predispose to HTG. METHODS: A Han Chinese patient with HTG-induced AP was assessed for genetic variants by Sanger sequencing of the entire coding and flanking sequences of the above five genes. RESULTS: The patient was a 32-year-old man with severe obesity (Body Mass Index = 35) and heavy smoking (ten cigarettes per day for more than ten years). At the onset of AP, his serum triglyceride concentration was elevated to 1450.52 mg/dL. We sequenced the entire coding and flanking sequences of the LPL, APOC2, APOA5, GBIHBP1 and LMF1 genes in the patient. We found no putative deleterious variants, with the exception of a novel and heterozygous nonsense variant, c.1024C > T (p.Arg342*; rs776584760), in exon 7 of the LMF1 gene. CONCLUSIONS: This is the first time that a heterozygous LMF1 nonsense variant was found in a HTG-AP patient with severe obesity and heavy smoking, highlighting an important interplay between genetic and lifestyle factors in the etiology of HTG.


Assuntos
Códon sem Sentido , Hipertrigliceridemia/complicações , Proteínas de Membrana/genética , Obesidade Mórbida/genética , Pancreatite/genética , Fumar/genética , Adulto , Predisposição Genética para Doença , Heterozigoto , Humanos , Hipertrigliceridemia/genética , Estilo de Vida , Masculino , Pancreatite/etiologia
8.
World J Surg ; 43(4): 1121-1128, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30569220

RESUMO

BACKGROUND AND AIMS: A variety of minimally invasive techniques have been proposed to replace open surgery for the treatment of infected pancreatic necrosis (IPN). In this study, we evaluate the feasibility and safety of the stent-assisted percutaneous endoscopic necrosectomy (SAPEN) procedure. METHODS: Data were collected on all patients who underwent the SAPEN procedure between October 2017 and March 2018. The demographic and clinical characteristics of the study patients were analyzed. A composite primary endpoint of major complications and/or death was used. Three different cases were selected to illustrate different technical aspects of the SAPEN procedure. RESULTS: The placement of a percutaneous stent was successful in all of the 23 patients (17 males, six females). IPN was successfully managed in 16/23 (70%) patients, with the need for open surgery in seven patients (30%), with a median of two (range 1-5) SAPEN procedures. No significant procedure-related complications occurred. Overall 11/23 (48%) patients had a major complication and/or death. CONCLUSIONS: In conclusion, the SAPEN procedure was effective in treating IPN without adding extra procedural risk. The role and benefits of the SAPEN procedure now need to be demonstrated in larger controlled study.


Assuntos
Drenagem/métodos , Endoscopia do Sistema Digestório/métodos , Infecções Intra-Abdominais/cirurgia , Pancreatite Necrosante Aguda/cirurgia , Stents , Adulto , Humanos , Masculino , Projetos Piloto , Estudos Retrospectivos
9.
Dig Dis Sci ; 64(2): 544-552, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30327961

RESUMO

INTRODUCTION: The association between early resuscitation volume and clinical outcomes remains controversial in acute pancreatitis. In the present study, we aimed to identify the association between resuscitation volume and the development of acute kidney injury (AKI) and other clinical outcome metrics. METHODS: Patients admitted to our center with moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) from January 2009 to December 2013 were reviewed retrospectively. Patients were stratified into two groups on the basis of the volume of fluid infused during the first 24 h. The primary clinical endpoint was incidence of AKI. Moreover, AKI lasting time, utilization of continuous renal replacement therapy and lasting time, creatinine increase, and other clinical metrics were also compared. The potential risk factors of new-onset AKI were also analyzed. RESULTS: A total of 179 patients were included, and aggressive fluid resuscitation (≥ 4 l) was associated with increased incidence of AKI compared with nonaggressive group (53.12% vs. 25.64%, p = 0.008), longer AKI lasting time (p = 0.038), and increased creatinine increase (p < 0.001) during hospitalization. Moreover, utilization of continuous renal replacement therapy was more frequent in aggressive group (40.63% vs. 24.36%, p = 0.108), and the lasting time of continuous renal replacement therapy was also longer (p = 0.181), though both not statistically different. Moreover, in multivariate analysis, aggressive resuscitation [OR 4.36 (1.52-13.62); p = 0.001] and chloride exposure [OR 2.53 (1.26-5.21); p = 0.012] in the first 24 h were risk factors of new-onset AKI. CONCLUSION: In patients with MSAP and SAP, aggressive fluid resuscitation was associated with increased incidence and longer duration of AKI. Moreover, aggressive resuscitation and chloride exposure in the first 24 h were risk factors of new-onset AKI.


Assuntos
Lesão Renal Aguda/epidemiologia , Hidratação/métodos , Pancreatite/terapia , Terapia de Substituição Renal/estatística & dados numéricos , Ressuscitação/métodos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/terapia , Adulto , Creatinina/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença
10.
Pancreatology ; 19(1): 136-142, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30473463

RESUMO

OBJECTIVE: We aimed to evaluate whether early (first 48 h) hyperchloremia and/or the change of serum chloride concentration are associated with acute kidney injury (AKI) in patients with moderately severe and severe acute pancreatitis (MSAP and SAP). METHODS: We retrospectively collected the data of patients with a primary diagnosis of MSAP or SAP from a tertiary center between January 2014 and June 2017. Consecutive chloride levels within the first 48 h after admission were retrieved for further calculation. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to assess the relationship between hyperchloremia and AKI. RESULTS: 145 patients were enrolled for analysis, of whom 33.5% (47/145) developed hyperchloremia during the observation period. The incidence of AKI was significantly higher in the hyperchloremia group (40.4% vs 7.1%; p < 0.001). On multivariate analysis, the increase in serum chloride (Δ[Cl-]) was independently associated with AKI [OR = 1.32 (1.00-1.74)], as was chloride exposure [OR = 1.01 (1.00-1.02)], and these associations were found to be stronger in patients identified as predicted SAP (PSAP). Moreover, even in patients without hyperchloremia, increase in serum chloride (Δ[Cl-]) was still associated with AKI [OR = 1.65 (1.18-2.32)]. Area under the curve of the ROC curve (AUCROC) analysis found that Δ[Cl-] is a good predictor of AKI with an optimal cutoff point at 3.5 mmol/L, showing an AUCROC of 0.81. CONCLUSION: Hyperchloremia is common in patients with AP and Δ[Cl-] and chloride exposure during the first 48 h were independent risk factors for AKI in MSAP and SAP patients.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Cloretos/sangue , Cloretos/toxicidade , Pancreatite/complicações , Lesão Renal Aguda/sangue , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pancreatite/sangue , Estudos Retrospectivos
12.
Expert Opin Biol Ther ; 18(sup1): 53-60, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30063854

RESUMO

INTRODUCTION: Severe acute pancreatitis (SAP) is an acute inflammatory disease with prolonged clinical course, which is complicated by the presence of persistent organ failure and severe infection. Infection mainly occurs in the late phase of SAP and it is found to be the main cause of death. Therefore, developing strategies for the prevention of SAP-related infection has been a crucial approach to improve patients' outcomes. Due to remarkable immune-cells-regulating properties, thymosin α1 has been recognized as a promising immune therapy, especially in several infectious diseases. Recently, thymosin α1 has been given high expectations to exert clinical benefits in the prevention of SAP-related infection. AREAS COVERED: The review of currently available strategies for SAP-related infection prevention and the use of thymosin α1 in SAP patients. EXPERT OPINION: The current available strategies achieve limited success for preventing SAP-related infection. A possible explanation is that the trigger of infection, immunosuppression has not been concurrently resolved. The application of thymosin α1 in a clinical study showed a prophylactic effect against SAP-related infection. However, the use of thymosin α1 in SAP patients is still at an early stage of clinical investigation and requires high-quality and large sample size evidences.


Assuntos
Quimioprevenção/métodos , Pancreatite/tratamento farmacológico , Sepse/prevenção & controle , Timalfasina/uso terapêutico , Doença Aguda , Humanos , Pancreatite/patologia , Índice de Gravidade de Doença
13.
Am J Transl Res ; 10(7): 2015-2025, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30093939

RESUMO

Clinical studies have confirmed that patients with diabetes had an elevated risk of acute pancreatitis (AP) and diabetes was associated with increased severity and mortality in patients with AP. However, these studies failed to prove a cause-and-effect relationship between diabetes and AP. In the present study, we for the first time have evaluated the effects of diabetes on AP by adopting a type 2 diabetes animal model db/db mice and investigated the possible underlying mechanisms. The results showed that in comparison to wide type (WT) mice, db/db mice showed exacerbated pancreatic and pulmonary injuries, elevated serum amylase and lipase levels, increased myeloperoxidase (MPO) expressions in pancreatic and pulmonary tissues as well as increased apoptotic acinar cells after AP induction. Furthermore, we observed that NLRP3 inflammasome in pancreatic tissues was remarkably activated in db/db mice compared with WT mice. In addition, we also found that diabetes could increase the susceptibility of mice to AP. Taken together, our results indicated that diabetes could predispose and aggravate the disease severity of AP potentially via promoting the activation of NLRP3 inflammasome pathway.

14.
Gastroenterol Res Pract ; 2018: 3826084, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30057599

RESUMO

Objective: Severe acute pancreatitis (SAP) patients usually develop persistent organ dysfunction which causes the majority of deaths. It is important for SAP patients to receive centralized diagnosis and treatment in an experienced tertiary center. China, as a vast country with uneven distribution of medical resources, should take advantage of air medical transportation to meet the challenge of patient transfer among different regions. The aim of this study was to evaluate the safety and effectiveness of air transport for SAP patients via extra long distance. Methods: This was a retrospective analysis of all air medical transportations for SAP patients admitted to Jinling Hospital from January 2010 to December 2016. The general characteristics, transportation process, and clinical outcomes of these patients were recorded, and the safety and effectiveness of air transport were evaluated. Results: All the 20 SAP patients were successfully transferred by chartered aircraft without any occurrence of severe transport-associated complications. The mean transport time was 5.86 hours and the average transport distance was 1530 kilometers. The majority of SAP patients got timely intervention and the ultimate mortality rate was 15%. Conclusions: Air medical transport appears to be safe and effective for SAP patients with vital organ dysfunctions during the extra long-distance transportation.

15.
Biochem Biophys Res Commun ; 503(1): 38-44, 2018 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-29859191

RESUMO

Bile acids receptor TGR5 and its agonist INT-777, which has been found to be involved in the NLRP3 inflammasome pathway, play an important role in inflammatory diseases. However, the role of INT-777 in acute pancreatitis (AP) has not been reported. In this present study, we found that TGR5 was expressed in pancreatic tissue and increased after AP onset induced by caerulein and further evaluated the impact of INT-777 on the severity of AP. The results showed that INT-777 could reduce the severity of AP in mice, which was manifested as decreased pancreatic tissue damage as well as the decrease of serum enzymes (amylase and lipase), pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and the expression of necrosis related proteins (RIP3 and p-MLKL). Furthermore, we found that INT-777 reduced the reactive oxygen species (ROS) production in pancreatic acinar cells and inhibited the activation of NLRP3 inflammasome pathway. In conclusion, our data showed that INT-777 could protect pancreatic acinar cell against necrosis and reduce the severity of AP, which may be mediated by inhibiting ROS/NLRP3 inflammasome pathway.


Assuntos
Ácidos Cólicos/farmacologia , Pancreatite/prevenção & controle , Receptores Acoplados a Proteínas-G/agonistas , Células Acinares/efeitos dos fármacos , Células Acinares/metabolismo , Células Acinares/patologia , Animais , Ceruletídeo/toxicidade , Modelos Animais de Doenças , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Necrose , Pâncreas Exócrino/efeitos dos fármacos , Pâncreas Exócrino/metabolismo , Pâncreas Exócrino/patologia , Pancreatite/metabolismo , Pancreatite/patologia , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/metabolismo
16.
Mediators Inflamm ; 2018: 3232491, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29849486

RESUMO

Background: Naringenin (Nar) is a type of flavonoid and has been shown to have anti-inflammatory and antioxidative properties. However, the effects of Nar on acute pancreatitis (AP) have not been well studied. In this study, we aimed to investigate the function of Nar in a mouse model of AP. Methods: Mild acute pancreatitis (MAP) was induced by caerulein (Cae), and severe acute pancreatitis (SAP) was induced by L-arginine in mice. Nar was administered intraperitoneally at doses of 25, 50, or 100 mg/kg following MAP induction and at a dose of 100 mg/kg following SAP induction. The serum levels of cytokines, lipase, and amylase were determined, and pancreatic and pulmonary tissues were harvested. Results: The serum levels of amylase, lipase, and cytokines were significantly decreased in both MAP and SAP models after Nar treatment. The malondialdehyde (MDA) levels of the pancreatic tissue was significantly reduced in both MAP and SAP after Nar treatment. In contrast, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), total sulfhydryl (T-SH), and non-proteinsulthydryl (NP-SH) were markedly increased in both MAP and SAP after Nar treatment. The injury in pancreatic and pulmonary tissues was markedly improved as evidenced by the inhibited expression of myeloperoxidase, nod-like receptor protein 3, and interleukin 1 beta as well as the enhanced expression of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 in pancreatic tissues. Conclusions: Nar exerted protective effects on Cae-induced MAP and L-arginine-induced SAP in mice, suggesting that Nar may be a potential therapeutic intervention for AP.


Assuntos
Flavanonas/uso terapêutico , Heme Oxigenase-1/metabolismo , Proteínas de Membrana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pancreatite/tratamento farmacológico , Doença Aguda , Amilases/sangue , Animais , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Ceruletídeo/toxicidade , Citocinas/sangue , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Glutationa Transferase/sangue , Lipase/sangue , Masculino , Camundongos , Pancreatite/sangue , Pancreatite/induzido quimicamente
18.
Medicine (Baltimore) ; 97(22): e10713, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29851776

RESUMO

Endocrine pancreatic insufficiency secondary to acute pancreatitis (AP) drew increasing attention in the recent years. The aim of the present study was to assess the impact of pancreatic necrosis and organ failure on the risk of developing new-onset diabetes after AP.The follow-up study was conducted for patients recovered from AP in the treatment center of Jinling Hospital. Endocrine function was evaluated by simplified oral glucose tolerance test (OGTT). Pancreatic necrosis was examined by abdominal contrast-enhanced CT (CECT) scan during hospitalization. The data including APACHE II score, Balthazar's score, organ failure (AKI and ARDS) was also collected from the medical record database. All patients were divided into group diabetes mellitus (DM) and group non-DM according to the endocrine function and group pancreatic necrosis (PN) and persistent organ failure (OF), group PN and non-OF, group non-PN and OF, and group non-PN and non-OF according to the occurrence of pancreatic necrosis and persistent organ failure.Around 256 patients were included for the final analysis. 154 patients (60.2%) were diagnosed with DM (include impaired glucose tolerance, IGT), while 102 patients (39.8%) were deemed as normal endocrine function. APACHE II score and Balthazar score of the patients in the group DM were significant higher than those in the non-DM group (F = 6.09, P = .01; F = 10.74, P = .001). The incidence of pancreatic necrosis in group DM and group non-DM was, respectively, 64.7% and 53.0% (χ = 3.506, P = .06). The patients underwent necrosis debridement by percutaneous catheter drainage (PCD) and/or the operative necrosectomy (ON) were more likely to developed new onset DM than the patients without PCD or ON (χ = 2.385, P = .02). The morbidity of new-onset DM after AP gradually increased from group non-PN and non-OF, group non-PN and OF, group PN and non-OF to group PN and OF in order (χ = 4.587, P = .03). The value of HOMA-IR of patients at follow-up time was significant higher in group DM than group non-DM (F = 13.414, P = .000).Patients with both PN and persistent OF may were at increased risk of developing new-onset diabetes after AP. Insulin resistance could be the pivotal mechanism of the development of diabetes.


Assuntos
Diabetes Mellitus/diagnóstico , Insuficiência Pancreática Exócrina/diagnóstico , Pancreatite Necrosante Aguda/complicações , Índice de Gravidade de Doença , APACHE , Doença Aguda , Adulto , China/epidemiologia , Desbridamento/métodos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/etiologia , Drenagem/métodos , Insuficiência Pancreática Exócrina/complicações , Insuficiência Pancreática Exócrina/etiologia , Feminino , Teste de Tolerância a Glucose/métodos , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Pancreatite Necrosante Aguda/diagnóstico por imagem , Pancreatite Necrosante Aguda/patologia , Pancreatite Necrosante Aguda/cirurgia , Risco , Tomógrafos Computadorizados
19.
Biochem Biophys Res Commun ; 495(4): 2439-2447, 2018 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-29269298

RESUMO

OBJECTIVE: Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms. METHODS: Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20 µg/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1ß, and interleukin (IL)-1ß in pancreatic tissue was detected by Western blot and real-time PCR. RESULTS: Dexmedetomidine at 20 µg/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1ß, IL-6, and tumor necrosis factor (TNF)-α, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20 µg/kg significantly down-regulated the expression of NLRP3, pro-IL-1ß, and IL-1ß in pancreatic tissue, but up-regulated the expression of NET in both mouse models. CONCLUSION: Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression.


Assuntos
Dexmedetomidina/administração & dosagem , Fatores Imunológicos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/imunologia , Pancreatite/tratamento farmacológico , Pancreatite/imunologia , Animais , Anti-Inflamatórios/administração & dosagem , Citocinas/imunologia , Relação Dose-Resposta a Droga , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pancreatite/diagnóstico , Resultado do Tratamento , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia
20.
Shock ; 50(3): 265-272, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29200137

RESUMO

INTRODUCTION: Increased circulating endothelial progenitor cells (cEPC) have been observed in patients with vascular injury associated with sepsis and acute lung injury. However, a role for cEPC in severe acute pancreatitis (SAP) remains unclear. We therefore conducted a prospective study to study whether the quantities of cEPC can predict persistent organ failure (POF) in patients with predicted SAP. METHODS: A total of 42 predicted SAP patients who were admitted within 24 h after symptom onset and 10 healthy control subjects were enrolled in our study. The proportions of cEPC were analyzed based on flow cytometry simultaneously. Vascular endothelial growth factor (VEGF) levels were measured by enzyme-linked immunosorbent assay. RESULTS: The percentage of cEPC was significantly higher in patients with predicted SAP compared with healthy controls. Similarly, the levels of VEGF in peripheral blood were also significantly higher in predicted SAP patients than in the controls. Notably, patients with POF had lower proportion of cEPC compared with patients with transient organ failure (TOF). In contrast, patients with POF had a significantly higher level of VEGF compared with TOF. Of note, the percentages of cEPC were significantly inversely correlated with disease severity scores. More importantly, cEPC showed an excellent discriminative power for predicting POF among predicted SAP patients, whereas plasma VEGF and disease severity scores showed moderate accuracy in predicting future POF. CONCLUSIONS: Peripheral EPC as a novel biomarker is elevated and may aid to predict the development of POF in patients with predicted SAP.


Assuntos
Células Progenitoras Endoteliais , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/etiologia , Pancreatite/sangue , Pancreatite/complicações , Doença Aguda , Adulto , Idoso , Biomarcadores/sangue , Contagem de Células Sanguíneas , Citometria de Fluxo , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
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