PCSK9对急性胰腺炎局部并发症及不良预后事件的预测价值
|
摘要
目的:评估前蛋白转化酶枯草杆菌蛋白酶Kexin 9型(PCSK9)在急性胰腺炎(AP)早期诊断及其局部并发症中的预测价值,并分析PCSK9作为AP预后评价指标的可行性。方法:按照新亚特兰大诊断标准收集经临床及影像学诊断为AP的患者46例,分组分层为轻度胰腺炎(MAP)、中度胰腺炎(MSAP)及重度胰腺炎(SAP)。在患者入院当日(d0)、第3天(d3)和第10天(d10)采用酶联免疫吸附法(ELISA)检测血清PCSK9的浓度,同时收集血生化指标(炎症因子、肝功能、淀粉酶、脂肪酶、血脂代谢等);并随访患者入院时及治疗后的影像学资料,按照CT严重程度评分(the Balthazar score)区分局部并发症;以40例年龄相近的胃部ESD术前患者血清作为正常对照。采用IBM SPSS Statistics 20.0软件进行统计学分析。结果:与对照组相比,在d0,PCSK9在AP中升高;且进一步分层分析显示PCSK9升高在MAP、MSAP及SAP组差异均有统计学意义(P<0.05);PCSK9是AP局部并发症发生的独立危险因素。Logistic回归分析显示,PCSK9是AP局部并发症发生的独立危险因素;PCSK9水平在d3～d10下降不明显是不良预后事件发生的独立危险因素;疾病发展过程中PCSK9水平升高与血脂代谢各项指标无明显关联性。结论:PCSK9可作为AP早期诊断的新指标;PCSK9高水平可能是AP局部并发症的促进因素,具有预测意义;PCSK9亦可作为AP的预后评价指标。
Objective: To investigate role of serum proprotein convertase subtilisin/kexin type 9(PCSK9) level in predicting local complications and clinical prognosis in acute pancreatitis(AP). Methods: A total of 46 AP patients were enrolled, and stratified as mild(MAP), moderately severe(MSAP), and severe(SAP) groups following 2012 revised Atlanta classification system. Serum samples were collected on d0, d3, and d10, and PCSK9 level was evaluated using the ELISA method. Other biochemistry profile and imaging data were collected at the same time. Local complications were determined following CT severity score(the Balthazar score). Serum samples of 40 age-matched patients prior to ESD procedures with proven negative results were collected as the controls. Results: On d0, the PCSK9 serum level was significantly elevated in AP patient as compared with the control group. Following stratified analysis revealed that the PCSK9 levels were different among the MAP, MSAP, and SAP groups(P<0.05). Logistic regression revealed that PCSK9 serum level on d0 was independent risk factor for local complication in acute pancreatitis, and non-obvious decrease of serum PCSK9 level on d3 to d10 was independent risk factor for adverse clinical outcome. Spearman's correlation revealed that elevation of PCSK9 level was dispensable to lipid elevation in AP. Conclusions: PCSK9 can be used as a novel predictive parameter for local complications and prognosis in AP.
Objective: To investigate role of serum proprotein convertase subtilisin/kexin type 9(PCSK9) level in predicting local complications and clinical prognosis in acute pancreatitis(AP). Methods: A total of 46 AP patients were enrolled, and stratified as mild(MAP), moderately severe(MSAP), and severe(SAP) groups following 2012 revised Atlanta classification system. Serum samples were collected on d0, d3, and d10, and PCSK9 level was evaluated using the ELISA method. Other biochemistry profile and imaging data were collected at the same time. Local complications were determined following CT severity score(the Balthazar score). Serum samples of 40 age-matched patients prior to ESD procedures with proven negative results were collected as the controls. Results: On d0, the PCSK9 serum level was significantly elevated in AP patient as compared with the control group. Following stratified analysis revealed that the PCSK9 levels were different among the MAP, MSAP, and SAP groups(P<0.05). Logistic regression revealed that PCSK9 serum level on d0 was independent risk factor for local complication in acute pancreatitis, and non-obvious decrease of serum PCSK9 level on d3 to d10 was independent risk factor for adverse clinical outcome. Spearman's correlation revealed that elevation of PCSK9 level was dispensable to lipid elevation in AP. Conclusions: PCSK9 can be used as a novel predictive parameter for local complications and prognosis in AP.
引文
[ 1 ] LERCH M M,ADLER G.Pathophysiology of acute pancreatitsis[J].Digestive Surgery,1994,11(3-6):186-192.
[ 2 ] BROWN A,YOUNG B,MORTON J,et al.Are health related outcomes in acute pancreatitis improving?An analysis of national trends in the U.S.from 1997 to 2003[J].JOP,2008,9(4):408-414.
[ 3 ] SHAHEEN N J.The burden of gastrointestinal and liver diseases[M].GI Epidemiology,Blackwell Publishing Ltd.,2008:1-101.
[ 4 ] CHAUHAN S,FORSMARK C E.The difficulty in predicting outcome in acute pancreatitis[J].Am J Gastroenterol,2010,105(2):443-445.
[ 5 ] AMMORI B J,LEEDER P C,KING R F,et al.Early increase in intestinal permeability in patients with severe acute pancreatitis:correlation with endotoxemia,organ failure,and mortality[J].J Gastrointest Surg,1999,3(3):252-262.
[ 6 ] SCHIETROMA M,PESSIA B,CARLEI F,et al.Intestinal permeability and systemic endotoxemia in patients with acute pancreatitis[J].Ann Ital Chir,2016,87:138-144.
[ 7 ] SHARMA B,SRIVASTAVA S,SINGH N,et al.Role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis:a double-blind randomized controlled trial[J].J Clin Gastroenterol,2011,45(5):442-448.
[ 8 ] BOSE S M,VERMA G R,MAZUMDAR A,et al.Significance of serum endotoxin and antiendotoxin antibody levels in predicting the severity of acute pancreatitis[J].Surg Today,2002,32(7):602-607.
[ 9 ] LAGACE T A,CURTIS D E,GARUTI R,et al.Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice[J].J Clin Invest,2006,116(11):2995-3005.
[10] FEINGOLD K R,MOSER A H,SHIGENAGA J K,et al.Inflammation stimulates the expression of PCSK9[J].Biochem Biophys Res Commun,2008,374(2):341-344.
[11] BOYD J H,FJELL C D,RUSSELL J A,et al.Increased plasma PCSK9 levels are associated with reduced endotoxin clearance and the development of acute organ failures during sepsis[J].J Innate Immun,2016,8(2):211-220.
[12] DWIVEDI D J,GRIN P M,KHAN M,et al.Differential expression of PCSK9 modulates infection,inflammation,and coagulation in a murine model of sepsis[J].Shock,2016,46(6):672-680.
[13] CAI Y,LU D,ZOU Y,et al.Curcumin protects against intestinal origin endotoxemia in rat liver cirrhosis by targeting PCSK9[J].J Food Sci,2017,82(3):772-780.
[14] WALLEY K R.Role of lipoproteins and proprotein convertase subtilisin/kexin type 9 in endotoxin clearance in sepsis[J].Curr Opin Crit Care,2016,22(5):464-469.
[15] BERGER J M,LOZA VALDES A,GROMADA J,et al.Inhibition of PCSK9 does not improve lipopolysaccharide-induced mortality in mice[J].J Lipid Res,2017,58(8):1661-1669.
[16] SHARMA M,SACHDEV V,SINGH N,et al.Alterations in intestinal permeability and endotoxemia in severe acute pancreatitis[J].Trop Gastroenterol,2012,33(1):45-50.
[17] CHOW S C,SHAO J,WANG H.A note on sample size calculation for mean comparisons based on noncentral t-statistics[J].J Biopharm Stat,2002,12(4):441-456.
[18] NAWAZ H,KOUTROUMPAKIS E,EASLER J,et al.Elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis[J].Am J Gastroenterol,2015,110(10):1497-1503.
[19] WAN J,HE W,ZHU Y,et al.Stratified analysis and clinical significance of elevated serum triglyceride levels in early acute pancreatitis:a retrospective study[J].Lipids Health Dis,2017,16(1):124.
[20] TOPCHIY E,CIRSTEA M,KONG H J,et al.Lipopolysaccharide is cleared from the circulation by hepatocytes via the low density lipoprotein receptor[J].PLoS One,2016,11(5):e0155030.
[ 2 ] BROWN A,YOUNG B,MORTON J,et al.Are health related outcomes in acute pancreatitis improving?An analysis of national trends in the U.S.from 1997 to 2003[J].JOP,2008,9(4):408-414.
[ 3 ] SHAHEEN N J.The burden of gastrointestinal and liver diseases[M].GI Epidemiology,Blackwell Publishing Ltd.,2008:1-101.
[ 4 ] CHAUHAN S,FORSMARK C E.The difficulty in predicting outcome in acute pancreatitis[J].Am J Gastroenterol,2010,105(2):443-445.
[ 5 ] AMMORI B J,LEEDER P C,KING R F,et al.Early increase in intestinal permeability in patients with severe acute pancreatitis:correlation with endotoxemia,organ failure,and mortality[J].J Gastrointest Surg,1999,3(3):252-262.
[ 6 ] SCHIETROMA M,PESSIA B,CARLEI F,et al.Intestinal permeability and systemic endotoxemia in patients with acute pancreatitis[J].Ann Ital Chir,2016,87:138-144.
[ 7 ] SHARMA B,SRIVASTAVA S,SINGH N,et al.Role of probiotics on gut permeability and endotoxemia in patients with acute pancreatitis:a double-blind randomized controlled trial[J].J Clin Gastroenterol,2011,45(5):442-448.
[ 8 ] BOSE S M,VERMA G R,MAZUMDAR A,et al.Significance of serum endotoxin and antiendotoxin antibody levels in predicting the severity of acute pancreatitis[J].Surg Today,2002,32(7):602-607.
[ 9 ] LAGACE T A,CURTIS D E,GARUTI R,et al.Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice[J].J Clin Invest,2006,116(11):2995-3005.
[10] FEINGOLD K R,MOSER A H,SHIGENAGA J K,et al.Inflammation stimulates the expression of PCSK9[J].Biochem Biophys Res Commun,2008,374(2):341-344.
[11] BOYD J H,FJELL C D,RUSSELL J A,et al.Increased plasma PCSK9 levels are associated with reduced endotoxin clearance and the development of acute organ failures during sepsis[J].J Innate Immun,2016,8(2):211-220.
[12] DWIVEDI D J,GRIN P M,KHAN M,et al.Differential expression of PCSK9 modulates infection,inflammation,and coagulation in a murine model of sepsis[J].Shock,2016,46(6):672-680.
[13] CAI Y,LU D,ZOU Y,et al.Curcumin protects against intestinal origin endotoxemia in rat liver cirrhosis by targeting PCSK9[J].J Food Sci,2017,82(3):772-780.
[14] WALLEY K R.Role of lipoproteins and proprotein convertase subtilisin/kexin type 9 in endotoxin clearance in sepsis[J].Curr Opin Crit Care,2016,22(5):464-469.
[15] BERGER J M,LOZA VALDES A,GROMADA J,et al.Inhibition of PCSK9 does not improve lipopolysaccharide-induced mortality in mice[J].J Lipid Res,2017,58(8):1661-1669.
[16] SHARMA M,SACHDEV V,SINGH N,et al.Alterations in intestinal permeability and endotoxemia in severe acute pancreatitis[J].Trop Gastroenterol,2012,33(1):45-50.
[17] CHOW S C,SHAO J,WANG H.A note on sample size calculation for mean comparisons based on noncentral t-statistics[J].J Biopharm Stat,2002,12(4):441-456.
[18] NAWAZ H,KOUTROUMPAKIS E,EASLER J,et al.Elevated serum triglycerides are independently associated with persistent organ failure in acute pancreatitis[J].Am J Gastroenterol,2015,110(10):1497-1503.
[19] WAN J,HE W,ZHU Y,et al.Stratified analysis and clinical significance of elevated serum triglyceride levels in early acute pancreatitis:a retrospective study[J].Lipids Health Dis,2017,16(1):124.
[20] TOPCHIY E,CIRSTEA M,KONG H J,et al.Lipopolysaccharide is cleared from the circulation by hepatocytes via the low density lipoprotein receptor[J].PLoS One,2016,11(5):e0155030.