AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to ...AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.展开更多
目的研究腹内压与重症急性胰腺炎伴肠屏障功能障碍相关性,探讨腹内压变化对重症急性胰腺炎伴肠屏障功能障碍患者病情与预后的评价价值。方法选择重症急性胰腺炎伴肠屏障功能障碍患者60例,其中将腹内压≤12 mm H2O的13例患者设为无腹内...目的研究腹内压与重症急性胰腺炎伴肠屏障功能障碍相关性,探讨腹内压变化对重症急性胰腺炎伴肠屏障功能障碍患者病情与预后的评价价值。方法选择重症急性胰腺炎伴肠屏障功能障碍患者60例,其中将腹内压≤12 mm H2O的13例患者设为无腹内高压组,将腹内压>12 mm H2O的32例患者设为腹内高压组,将腹内压≥20 mm H2O并且伴发新的器官功能衰竭患者15例设为腹腔间隔室综合征组;运用膀胱测压法对其腹内压进行监测,探讨腹内压与肠屏障功能障碍的相关性,观察接受手术治疗的患者在术前及术后腹内压与肠屏障功能障碍标志物血清内毒素与尿L/M比值之间的变化,计算腹内压变异率、急性生理与慢性健康评分Ⅱ(APACHEⅡ)与Ranson评分相关性及其对病死率的预测价值。结果无腹内高压组、腹内高压组与腹腔间隔室综合征组的肠屏障功能障碍标志物内毒素与尿L/M比较差异有统计学意义(P<0.05),其中以腹腔间隔室综合征组最高,无腹内高压组最低。经相关性比较,腹内压和内毒素(r=0.225,P=0.032)和尿L/M比较,差异有统计学意义(r=0.187,P=0.046)。与术前比较,本组36例行手术治疗的患者中存活的33例患者术后的第3天患者的腹内压、内毒素与尿L/M均明显减少(P<0.05)。采用Pearson相关性分析,腹内压变异率和APACHEⅡ、Ranson评分呈显著正相关(P<0.05),APACHEⅡ、Ranson评分呈显著正相关(P<0.05)。腹内压变异率对患者病死率预测值,即ROC曲线下面积达93.58%,略高于APACHEⅡ评分ROC曲线下面积89.58%,两者比较差异无统计学意义(P>0.05),但与Ranson评分ROC曲线下面积82.32%比较差异有统计学意义(P<0.05)。结论重症急性胰腺炎伴肠屏障功能障碍能够引发腹内高压与腹腔间隔室综合征,而腹内高压与腹腔间隔室综合征也会促进肠屏障功能发生损伤。腹内压变化能够反映出重症急性胰腺炎伴肠屏障功能障碍患者病情展开更多
基金Supported by The research grants from Shanghai Municipal Science and Technology CommissionNo.114119b2900+1 种基金Shanghai Municipal Key Laboratory of Pancreatic DiseaseNo.P2012006
文摘AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.
文摘目的研究腹内压与重症急性胰腺炎伴肠屏障功能障碍相关性,探讨腹内压变化对重症急性胰腺炎伴肠屏障功能障碍患者病情与预后的评价价值。方法选择重症急性胰腺炎伴肠屏障功能障碍患者60例,其中将腹内压≤12 mm H2O的13例患者设为无腹内高压组,将腹内压>12 mm H2O的32例患者设为腹内高压组,将腹内压≥20 mm H2O并且伴发新的器官功能衰竭患者15例设为腹腔间隔室综合征组;运用膀胱测压法对其腹内压进行监测,探讨腹内压与肠屏障功能障碍的相关性,观察接受手术治疗的患者在术前及术后腹内压与肠屏障功能障碍标志物血清内毒素与尿L/M比值之间的变化,计算腹内压变异率、急性生理与慢性健康评分Ⅱ(APACHEⅡ)与Ranson评分相关性及其对病死率的预测价值。结果无腹内高压组、腹内高压组与腹腔间隔室综合征组的肠屏障功能障碍标志物内毒素与尿L/M比较差异有统计学意义(P<0.05),其中以腹腔间隔室综合征组最高,无腹内高压组最低。经相关性比较,腹内压和内毒素(r=0.225,P=0.032)和尿L/M比较,差异有统计学意义(r=0.187,P=0.046)。与术前比较,本组36例行手术治疗的患者中存活的33例患者术后的第3天患者的腹内压、内毒素与尿L/M均明显减少(P<0.05)。采用Pearson相关性分析,腹内压变异率和APACHEⅡ、Ranson评分呈显著正相关(P<0.05),APACHEⅡ、Ranson评分呈显著正相关(P<0.05)。腹内压变异率对患者病死率预测值,即ROC曲线下面积达93.58%,略高于APACHEⅡ评分ROC曲线下面积89.58%,两者比较差异无统计学意义(P>0.05),但与Ranson评分ROC曲线下面积82.32%比较差异有统计学意义(P<0.05)。结论重症急性胰腺炎伴肠屏障功能障碍能够引发腹内高压与腹腔间隔室综合征,而腹内高压与腹腔间隔室综合征也会促进肠屏障功能发生损伤。腹内压变化能够反映出重症急性胰腺炎伴肠屏障功能障碍患者病情
