血管活性肠肽对急性坏死性胰腺炎大鼠肠黏膜屏障功能的影响

目的 探讨血管活性肠肽(VIP)对ANP大鼠肠黏膜损伤的影响.方法 54只SD大鼠随机分成假手术组(SO)、ANP组和VIP组,每组分制模后1 h、6 h、12 h 3个时间点,各6只.采用4%牛磺胆酸钠胰胆管逆行注射制备ANP模型,VIP组在制模后5 min腹腔内注射VIP 5 nmol.ELISA法检测血浆及肠组织匀浆VIP水平;MB-80微生物快速动态检测系统检测血浆内毒素水平;RT-PCR法检测肠黏膜组织TNF-α、IL-6、IL-10 mRNA表达;肠黏膜行病理学检查.结果 ANP组肠黏膜结构损害明显,VIP组病变减轻.ANP组血浆及肠黏膜VIP水平在制模后6 h分别为(49.582 ±3.735)pg/ml和(87.731 ±4.601)pg/g pro,均显著低于SO组(P＜0.05),制模后12 h分别为(65.192±5.785)pg/ml和(110.978 ±6.420)pg/g pro,高于SO组;ANP组制模后6 h血浆内毒素水平、肠黏膜TNF-α、IL-6、IL-10mRNA表达量分别为(29.570±5.127)pg/ml、0.861±0.081、1.150±0.187和0.786±0.102,均显著高于SO组(P＜0.05).VIP组制模后6 h血浆内毒素水平、肠黏膜TNF-α、IL-6 mRNA表达分别为(20.486 ±2.811)pg/ml、0.707 ±0.095和0.889 ±0.136,均较ANP组下降(P＜0.05);IL-10 mRNA表达为0.992 ±0.126,较ANP组增高(P＜0.05).结论 VIP对ANP大鼠肠黏膜损伤具有明显的保护作用.     

重组肠三叶因子对急性坏死性胰腺炎大鼠肠黏膜保护作用的研究

目的 探讨重组肠三叶因子(rITF)对急性坏死性胰腺炎(ANP)大鼠肠黏膜的保护作用及其机制.方法 SD雄性大鼠60只,按随机数字表法分为对照组、ANP组、rITF组,每组20只.逆行胰胆管注射5%牛黄胆酸钠100μl/100 g体重制备ANP模型.rITF组制模前后尾静脉注射rITF 0.5mg/100 g体重,对照组及ANP组注射等量生理盐水,术后12、24 h分批处死大鼠.取血检测淀粉酶含量,取末端回肠组织观察病理学改变并予评分、免疫组化法检测肠黏膜NF-κB活性,RT-PCR法检测肠黏膜TNF-α mRNA、ICAM-1 mRNA的表达.结果 ANP组和rITF组血淀粉酶水平较同时点对照组均显著升高.ANP组肠黏膜损伤评分较同时点对照组高(P＜0.05);ANP 12 h组较rITF 12 h组高(P＜0.05),但24 h组间评分无明显差异.对照组、ANP组与rITF组12 h肠黏膜NF-κB阳性细胞数分别为(26±4)个、(55±8)个、(49±4)个;回肠组织TNF-α mRNA相对表达量分别为0.050±0.005、1.040±0.031和0.792±0.0256;回肠组织ICAM-1 mRNA相对表达量分别为0.045±0.010、0.795±0.037和0.400±0.031.ANP组上述各项指标值均较对照组显著增加(P＜0.05或P＜0.01),而rITF下组又较ANP组均显著减少(P＜0.05).结论 重组肠三叶因子对ANP大鼠肠黏膜具有保护作用,其机制可能通过抑制肠黏膜NF-κB活化,下调TNF-αmRNA、ICAM-1 mRNA表达.     

乌司他丁对急性坏死性胰腺炎大鼠肠黏膜屏障的保护作用

目的 观察乌司他丁干预急性坏死性胰腺炎(ANP)大鼠后血TNF-α、二胺氧化酶(DAO)及肠黏膜组织紧密连接蛋白-1( zonula occludens-1,ZO-1)表达水平的变化,探讨其可能机制.方法 按完全随机法将SD雄性大鼠随机分为假手术组、ANP组及乌司他丁组.采用5％牛磺胆酸钠逆行注入胆胰管的方法制模.制模后6、24h取血检测TNF-α、DAO活性,胰腺及回肠组织常规病理检查,RT-PCR及免疫组化法检测回肠组织ZO-1 mRNA及蛋白的表达.结果 术后6h,ANP组胰腺大片坏死,大量炎细胞浸润;回肠黏膜绒毛上皮坏死、血管出血、炎细胞浸润.乌司他丁组的胰腺及回肠组织损伤较ANP组减轻.假手术组、ANP组、乌司他丁组术后6h的血TNF-α水平分别为(10.83±0.96)、( 181.89±4.93)、(128.23±2.40) ng/L;DAO活性分别为(354.79±3.67)、(117.21±5.58)、(282.98±9.12) U/L;回肠组织ZO-1蛋白表达量分别为(10.00±1.87)、(1.20±0.84)、(5.80±2.86)分;Z(O)-1 mRNA表达量为0.878±0.015、0.466±0.023、0.778±0.033.ANP组血TNF-α水平较假手术组明显升高,DAO活性、回肠组织ZO-1 mRNA及蛋白表达较对照组明显降低(P值均＜0.05);乌司他丁组的血TNF-α水平较ANP组降低,DAO活性、回肠组织ZO-1 mRNA及蛋白表达较ANP组明显升高(P值均＜0.05).结论 乌司他丁可能通过抑制TNF-α的过度释放、提高血浆中DAO活性,从而上调回肠组织中ZO-1 mRNA和蛋白表达,进而保护肠黏膜屏障.     

参附注射液对急性坏死性胰腺炎大鼠肠黏膜屏障保护作用的研究

目的 探讨参附注射液对ANP大鼠肠黏膜屏障的保护作用及机制.方法 雄性Wister大鼠21只,按随机分组法分为对照组、ANP组及参附治疗组(SF组),检测各组血浆MDA、MPO、SOD、TNF-α及小肠组织MDA、NO、MPO含量;免疫组化方法检测小肠组织NF-кB、ICAM-1及iNOS的蛋白表达.结果 ANP组血浆MPO、MDA、SOD、TNF-α量分别为(390.22±24.58)U/L、(41.79±5.68)nmol/L、(108.74±12.98)U/ml和(5.54±0.31)fmol/ml;肠组织MPO、MDA、NO含量分别为(270.96±31.86)U/g湿片、(7.61±2.02)nmol/g port和(51.21±46.98)μmoL/g prot;NF-кB、ICAM-1及iNOS蛋白阳性表达细胞数分别为85.68±7.79、0.218±0.035和0.098±0.016.SF组相对应值分别为(279.68±50.19)U/L、(31.07±3.92)nmoL/L、(123.45±7.94)U/L和(4.82±0.24)fmol/L:(214.46±19.64)U/g湿片、(2.88±1.48)nmol/g port和(20.27±7.92)μmol/g port;19.87±7.88、0.124±0.018和0.069±0.024.各项指标两组间差异均非常显著(P＜0.01).结论 参附注射液对ANP大鼠肠黏膜屏障有保护作用,其机制可能通过抑制NF-кB的表达,减少TNF-α、ICAM-1及iNOS的生成,从而改善肠道微循环,减轻肠组织炎症反应和减少氧自由基所致.     

谷氨酰胺对急性胰腺炎大鼠肠黏膜胰岛素样生长因子表达及肠黏膜屏障的影响

目的 观察急性坏死性胰腺炎（ANP）时肠黏膜屏障的损伤情况,以及谷氨酰胺（Gln）和胰岛素样生长因子（IGF）对肠黏膜屏障的保护作用.方法 成功诱导ANP模型雄性Wistar大鼠48只,随机分为ANP组和Gln组各24只,另取假手术组24只作为对照.Gln组每日以Gln灌胃2次,剂量为1.5g/（kg·d）;ANP组和假手术组以同等量的生理盐水灌胃.分别在模型制作术后3、6、24、48 h时间点杀死大鼠,取胰头和末端回肠3～5 cm放入液氮中保存.观察胰腺和肠黏膜组织形态学改变,测定肠黏膜中IGF-1的表达、血清中二氨氧化酶（DAO）活性和内毒素浓度.结果 ANP组大鼠肠黏膜屏障功能严重破坏,肠道通透性明显增加,肠黏膜损伤评分明显增加;血清内毒素浓度、DAO活性明显升高（P均＜0.01）.与ANP组比较,Gln组动物肠黏膜损伤减轻,损伤评分有所下降,血清内毒素水平、DAO活性下降（P均＜0.05）.ANP组IGF-1表达水平明显下降（P ＜0.05）;Gln组明显升高（P＜0.05）,同时肠黏膜屏障功能得到一定的改善.结论 ANP时肠黏膜屏障结构和功能存在严重破坏;Gln能一定程度上减轻肠黏膜屏障损伤并能维护其功能;IGF-1参与Gln对ANP肠黏膜屏障损伤的修复和维持.     

肠道菌群失衡在急性胰腺炎肠黏膜屏障损伤中的作用

急性胰腺炎(acute pancreatitis,AP)是临床常见的急腹症,其发病率呈逐年增高趋势.AP病情进展迅速,15％～20％的患者发展为重症急性胰腺炎(severe acute pancreatitis,SAP),病死率高达20％～30％.SAP常可导致肠道功能障碍,包括肠黏膜屏障损伤和肠道动力障碍,引起肠道细...     

重症急性胰腺炎对肠黏膜屏障损伤影响的研究进展

肠黏膜屏障功能是肠道的重要特征之一,大量研究表明重症急性胰腺炎(SAP)患者易发生肠屏障功能障碍,而肠屏障功能障碍又可进一步继发感染,甚至诱发和加重全身炎症反应综合征(SIRS)、多器官功能障碍综合征(MODS)。本文就SAP对肠黏膜屏障损伤影响的研究进展作一简要综述。     

微生态肠内营养治疗重症急性胰腺炎肠黏膜损伤的临床研究

目的观察微生态肠内营养对SAP肠黏膜损伤治疗和菌群紊乱的调节作用。方法40例SAP患者随机分为对照组和治疗组。对照组给予常规肠内营养,治疗组加用微生态制剂,治疗7d,检测患者血浆二胺氧化酶(DAO)、D-乳酸水平以及肠道菌群变化。结果治疗7d后,治疗组血浆DAO水平为(4.35±0.91)U/ml,较对照组的(5.45±2.19)U/ml明显下降(P<0.05);D-乳酸为(10.41±5.36)mg/L,与治疗前无显著性差异,但明显高于对照组的(5.53±2.05)mg/L(P<0.05);治疗组患者肠道双歧杆菌、乳杆菌的总数达(5.98±1.63)In/g和(7.23±1.94)In/g,较治疗前的(3.76±1.67)In/g和(3.91±1.82)In/g明显增加(P<0.05),肠道菌群比例接近正常,而对照组仍存在一定程度的菌群紊乱。结论微生态肠内营养具有减轻SAP肠黏膜损伤、调节肠道菌群微生态平衡、保护肠屏障功能的辅助治疗作用。     

微生态肠内营养治疗重症急性胰腺炎肠黏膜损伤的临床研究

目的 观察微生态肠内营养对SAP肠黏膜损伤治疗和菌群紊乱的调节作用.方法 40例SAP患者随机分为对照组和治疗组.对照组给予常规肠内营养,治疗组加用微生态制剂,治疗7 d,检测患者血浆二胺氧化酶(DAO)、D-乳酸水平以及肠道菌群变化.结果 治疗7 d后,治疗组血浆DAO水平为(4.35±0.91)U/ml,较对照组的(5.45±2.19)U/ml明显下降(P＜0.05);D-乳酸为(10.41±5.36)mg/L,与治疗前无显著性差异,但明显高于对照组的(5.53±2.05)mg/L(P＜0.05);治疗组患者肠道双歧杆菌、乳杆菌的总数达(5.98±1.63)In/g和(7.23±1.94)In/g,较治疗前的(3.76±1.67)In/g和(3.91±1.82)In/g明显增加(P＜0.05),肠道菌群比例接近正常,而对照组仍存在一定程度的菌群紊乱.结论 微生态肠内营养具有减轻SAP肠黏膜损伤、调节肠道菌群微生态平衡、保护肠屏障功能的辅助治疗作用.     

大黄对急性坏死性胰腺炎大鼠肠黏膜屏障及肠道菌群的作用研究

研究发现,重症急性胰腺炎（SAP）常并发肠黏膜屏障功能障碍（IBD）,出现肠道细菌易位,继发肠源性感染。感染相关并发症导致的病死人数占SAP患者病死总人数的80％。中药大黄作为一种溢清泻下的药物已应用于临床,但其详细机制不清。本研究旨在观察大黄对急性坏死性胰腺炎（ANP）大鼠肠黏膜屏障及肠道菌群的保护作用。     

急性冠脉综合征患者外周血HIF-1α水平及其临床价值

目的 观察急性冠脉综合征患者外周血低氧诱导因子-1α（HIF-1α）蛋白的表达水平,探讨其临床应用价值.方法 选取我院心内科住院患者作为研究对象,其中急性冠脉综合征（ACS）60例、稳定型心绞痛（UAP）30例,另选健康人（NC）30名为正常对照组.从静脉采取外周血,酶联免疫吸附法检测外周血中HIF-1α的浓度.结果 急性冠脉综合征组HIF-1α表达明显高于不稳定型心绞痛组、稳定型心绞痛组和正常对照组（25.46±10.39比20.89±12.9、12.38±6.9、10.96±7.29,P＜0.05）,稳定型心绞痛组与对照组比较差异无统计学意义.血清HIF-1α浓度与cTnI、CK、CK-MB均呈正相关.结论 急性冠脉综合征患者急性期外周血HIF-1α的表达明显增加,可能提示急性冠脉综合征患者硬化斑块不稳定,疾病进展.     

炎症性肠病中低氧诱导因子-1α表达的研究

目的 观察低氧诱导因子-1α(HIF-1α)在炎症性肠病的炎症组织中的表达,探讨HIF-1α在炎症性肠病发病机制中的调控作用。方法 取经过临床表现、内镜、病理、影像学等方法共同确诊的炎症性肠病活检的石蜡标本和肠癌手术切除标本残端的正常组织的石蜡标本,用枸橼酸-微波-SP-免疫组织化学方法检测HIF—1的表达情况,并分析HIF-1α表达状况与患者年龄、性别的关系。结果 溃疡性结肠炎中HIF-1α表达阳性率(73.39％±1.32)显著高于正常肠组织(2.44％±1.69％)(P<0.01),克隆氏病中HIF-1α表达阳性率(68.54％±1.39％)也显著高于正常肠组织(2.44％±1.69％)(P<0.01),溃疡性结肠炎和克隆氏病中HIF-1α的表达与患者的年龄、性别无显著的相关性(P>0.05)。结论 HIF-1α作为一种转录因子可能在炎症性肠病发病机制中充当重要角色。     

NF-κB、HMGB1在重症急性胰腺炎肠黏膜损伤中的时点表达及其意义

目的:探讨NF-κB、HMGB1在SAP大鼠肠黏膜损伤发生发展过程中的时点表达规律及其意义.方法:将70只SD大鼠随机分为A组(n=40)和S组(n=30),再分别按3、6、12、24、36h时点随机均等分成5个亚组.A组大鼠行逆行胰胆管匀速泵入5%牛磺胆酸钠建立SAP模型,S组大鼠开腹仅翻动十二指肠.两组大鼠均在建模后按时点开腹,门静脉取血检测AMY、DAO浓度,ELISA法和免疫组化法检测小肠黏膜NF-κB和HMGB1的表达.结果:(1)A组大鼠血DAO浓度随时点延迟逐渐增加;(2)肠黏膜NF-κB表达在3h最高,随时点延迟逐渐下降,24h、36h降至正常水平;(3)肠黏膜HMGB1表达6h开始明显升高,且随时点延迟逐渐增高,在24h最高,一直持续到36h仍然保持在较高水平.结论:(1)SAP大鼠早期即出现肠黏膜损伤;(2)SAP肠黏膜早期的损伤可能与小肠组织NF-κB的表达增加有关;(3)HMGB1作为晚期炎症介质可能介导了SAP肠黏膜损伤的发生发展;(4)HMGB1的调控可能受到了NF-κB的调节.     

蛋白酶激活受体-2在急性坏死性胰腺炎大鼠肠黏膜组织中的表达

目的 探讨蛋白酶激活受体-2(PAR-2)的表达与急性坏死性胰腺炎(ANP)大鼠肠黏膜屏障损伤的相关性.方法 制备ANP大鼠模型,采用免疫组织化学法、Western印迹法及RT-PCR方法检测假手术对照组和造模后6、12、24 h大鼠肠黏膜组织中PAR-2的表达.组间数据比较采用单因素方差分析.结果 免疫组织化学法显示,假手术对照组大鼠小肠黏膜组织中PAR-2的表达较微弱.ANP造模后,PAR-2阳性细胞表达数量明显增加,染色强度明显增强.造模后6、12、24 h的免疫组织化学评分分别为4.88±0.33、5.87±0.32、11.17±0.27,与假手术对照组(2.86±0.31)相比,差异有统计学意义(F=747.08,P＜0.01).假手术对照组大鼠小肠黏膜中PAR-2的mRNA和蛋白表达量均较少,随着ANP造模时间的延长,两者的表达水平均逐渐升高,造模后6、12、24 h,mRNA分别为0.56±0.03、0.69±0.03、1.05±0.05,蛋白分别为0.28±0.02、0.35±0.03、0.69土0.04;各时间点与假手术对照组相比,差异均有统计学意义(F=785.69、1177.82,P值均＜0.01).结论 PAR-2在ANP炎性反应中被激活,在肠黏膜屏障损伤的发生发展过程中发挥重要作用.     

Toll样受体4在猪急性坏死性胰腺炎肠道组织中的表达及其意义

目的:探讨猪急性坏死性胰腺炎(acute necrotizing pancreatitis,ANP)回肠组织中Toll样受体4(Toll-like receptor4,TLR4)的表达及其意义.方法:选择太湖梅山猪,随机分成对照组(C,n=4)、急性坏死性胰腺炎组(ANP,n=4).诱导制备ANP模型.用分光光度法检测血清及回肠组织匀浆中二胺氧化酶(DAO)活性;动态比浊法检测血浆内毒素水平;RT-PCR检测回肠黏膜组织TLR4、TNF-α及IL-6mRNA表达.结果:ANP组回肠组织DAO水平明显低于C组,血清中DAO明显升高(P<0.05).ANP组血浆内毒素水平较C组明显升高(P<0.05);回肠黏膜组织TLR4、TNF-α、IL-6mRNA在C组表达非常低,ANP组表达明显增加;TLR4mRNA表达水平与肠黏膜DAO水平呈负相关(r=-0.762,P=0.028),与血浆内毒素呈正相关(r=0.778,P=0.023).结论:ANP时回肠组织内TLR4mRNA表达上调,可能与ANP肠黏膜屏障功能障碍有关;其可能机制与TLR4介导激活核转录因子NF-αB信号转导途径有关.     

生长抑素和生长激素联用对兔重症急性胰腺炎肠黏膜屏障损伤的保护作用

目的 观察生长抑素(SS)和生长激素(GH)联合应用对重症急性胰腺炎(SAP)兔肠黏膜屏障损伤的保护作用,探讨其对治疗SAP的意义.方法 72只新西兰大白兔平均分为3组,SAP模型组(SAP组)、SS治疗组(SS组)以及SS和GH联合治疗组(SS+GH组).经胰管开口逆行注入5%牛磺胆酸钠溶液诱导兔SAP模型,造模后3组均每日予5%葡萄糖氯化钠(GNS)治疗,SS组造模后按3.5μg·kg-1·h-1持续48 h泵入SS治疗,SS+GH组造模后第1、24 h在持续泵入SS的基础上,按0.15 IU/kg皮下注射GH治疗.观察各组动物造模后第6、12、24、48小时血清淀粉酶、肿瘤坏死因子(TNF)-α,血浆二胺氧化酶水平的变化,观察兔胰腺和肠黏膜的病理学变化及存活率.采用SPSS 16.0统计软件进行分析,组间比较采用单因素方差分析.结果 SS+GH组兔血清TNF-α和血浆二胺氧化酶水平较SAP组和SS组均明显降低,造模后24 h[分别为(2.43±0.14)pg/ml和(4.61±0.45)U/L]和48 h[分别为(2.08±0.23)pg/rl和(3.75±0.47)U/L]较SS组[24 h分别为(2.80±0.30)pg/ml和(8.74±1.77)U/L,48 h分别为(2.45±0.12)pg/m1和(5.02±0.95)U/L]显著降低,差异均有统计学意义(P＜0.05).SS+GH组较SAP组和SS组兔肠黏膜炎性反应减轻,肠黏膜的完整性增加,胰腺组织炎性反应减轻,存活率提高,但血清淀粉酶在各时间点与SS组相比差异均无统计学意义.结论 SS和GH联合应用可增强兔肠黏膜屏障功能,改善SAP预后.

Abstract：

Objective To investigate the protective effect of somatostatin (SS)combined with growth hormone (GH) in treatment of intestinal mucosal barrier injury in rabbits with severe acute pancreatitis (SAP), as well as its clinical significance. Methods Seventy-two rabbits were equally assigned into model group (SAP group), SS treated group (SS group) and SS combined with GH treated group (SS + GH group). SAP models were induced by retro-injection of 5% sodium taurocholate into the pancreatic duct. After modeling, all rabbits were given 5 % glucose saline daily.The rabbits in SS group and SS+GH group were continuously Given SS (3.5μg·kg-1·h-1)for 48 hours. Besides, the rabbits in SS+GH group were subcutaneously injected with 0.15 IU/kg of GH at the 1st and the 24th hours after modeling. The levels of serum amylase, serum tumor necrosis factor-α (TNF-α) and plasma diamine oxidase were measured at the 6th, 12th, 24th and 48th hours after modeling. The pathological changes of pancreatic tissue and ileal mucosa were observed. Survival rate was calculated. Data were analyzed using SPSS 16.0 software. The univariate analysis was used to compare the difference among groups. Results In SS+GH group, the levels of serum TNF-α and plasma diamine oxidase were (2. 43 ± 0. 14) pg/ml and (4. 61 ± 0. 45) U/L at the 24th hour respectively, and were (2.08±0.23) pg/ml and (3.75±0.47) U/L at the 48th hour, respectively,which were lower than those in SAP group and SS group [(2.80 0.30) pg/ml and (8.74 ± 1.77)U/L, respectively, at the 24th hour; (2. 45±0.12) pg/ml and (5. 02±0.95) U/L, respectively, at the 48th hour)]with significant difference (P＜0.05). The inflammation in pancreas and ileal mucosa was alleviated, and the integrity of bowel mucosa was improved. Survival rate of SS+GH group was significantly higher than SAP group and SS group. There was no significant difference in level of serum amylase between SS+GH group and SS group. Conclusion The combination of SS with GH may enhance the function of intestinal mucosa barrier and improve the prognosis of SAP in rabbits.     

大黄甘草汤对高原急性坏死性胰腺炎合并肠损伤大鼠的影响

目的 观察大黄甘草汤对高原急性坏死性胰腺炎（P-ANP）并发肠损伤大鼠的治疗效果.方法 54只Wistar大鼠,由兰州市运至马衔山（海拔3848米）适应性喂养1个月.按完全随机法分为假手术组、P-ANP组、大黄甘草汤组,每组18只.采用逆行胰胆管注射4％牛磺胆酸钠方法制备P-ANP模型.大黄甘草汤组于造模前2h、造模后每12 h给予大黄甘草汤0.6 ml/100 g体质量灌胃,假手术组和P-ANP组给予等容积生理盐水灌胃.术后6、12、24 h分批处死大鼠,取胰腺及小肠组织行组织病理学检查并评分,透射电镜观察肠黏膜超微结构变化.采用ELISA法检测小肠组织IL-10、TNF-α表达水平.结果 造模后12 h,假手术组、P-ANP组、大黄甘草汤组的胰腺病理评分为（0.33±0.52）、（8.33±0.52）、（6.17±2.13）分;肠组织病理评分为（0.17±0.41）、（3.83±1.17）、（2.17±1.17）分.P-ANP组和大黄甘草汤组胰腺、小肠病理评分均显著高于假手术组（P值均＜0.01）,大黄甘草汤组又均显著低于同时间点的P-ANP组（P值均＜0.05）,且大黄甘草汤组肠组织和胰腺组织病理学损伤呈正相关（r =0.796,P＜0.01）.P-ANP组大鼠肠黏膜超微结构损伤严重,而大黄甘草汤组较P-ANP组损伤明显减轻.造模后12 h,假手术组、P-ANP组、大黄甘草汤组小肠组织IL-10水平分别为（136.68±13.98）、（762.21 ±79.58）、（896.36±84.87） pg/g,TNF-α水平分别为（353.05±76.21）、（1913.87±259.33）、（1481.58±231.47）pg/g,P-ANP组和大黄甘草汤组IL-10、TNF-α水平均较假手术组显著增高,大黄甘草汤组IL-10水平又较P-ANP组显著增高（P＜0.05）,但TNF-α水平则较P-ANP组显著降低（P＜0.05）.结论 大黄甘草汤可迅速改善P-ANP大鼠并发的肠损伤.     

生长抑素和生长激素联用对兔重症急性胰腺炎肠黏膜屏障损伤的保护作用

Objective To investigate the protective effect of somatostatin (SS)combined with growth hormone (GH) in treatment of intestinal mucosal barrier injury in rabbits with severe acute pancreatitis (SAP), as well as its clinical significance. Methods Seventy-two rabbits were equally assigned into model group (SAP group), SS treated group (SS group) and SS combined with GH treated group (SS + GH group). SAP models were induced by retro-injection of 5% sodium taurocholate into the pancreatic duct. After modeling, all rabbits were given 5 % glucose saline daily.The rabbits in SS group and SS+GH group were continuously Given SS (3.5μg·kg-1·h-1)for 48 hours. Besides, the rabbits in SS+GH group were subcutaneously injected with 0.15 IU/kg of GH at the 1st and the 24th hours after modeling. The levels of serum amylase, serum tumor necrosis factor-α (TNF-α) and plasma diamine oxidase were measured at the 6th, 12th, 24th and 48th hours after modeling. The pathological changes of pancreatic tissue and ileal mucosa were observed. Survival rate was calculated. Data were analyzed using SPSS 16.0 software. The univariate analysis was used to compare the difference among groups. Results In SS+GH group, the levels of serum TNF-α and plasma diamine oxidase were (2. 43 ± 0. 14) pg/ml and (4. 61 ± 0. 45) U/L at the 24th hour respectively, and were (2.08±0.23) pg/ml and (3.75±0.47) U/L at the 48th hour, respectively,which were lower than those in SAP group and SS group [(2.80 0.30) pg/ml and (8.74 ± 1.77)U/L, respectively, at the 24th hour; (2. 45±0.12) pg/ml and (5. 02±0.95) U/L, respectively, at the 48th hour)]with significant difference (P＜0.05). The inflammation in pancreas and ileal mucosa was alleviated, and the integrity of bowel mucosa was improved. Survival rate of SS+GH group was significantly higher than SAP group and SS group. There was no significant difference in level of serum amylase between SS+GH group and SS group. Conclusion The combination of SS with GH may enhance the function of intestinal mucosa barrier and improve the prognosis of SAP in rabbits.     

生长抑素和生长激素联用对兔重症急性胰腺炎肠黏膜屏障损伤的保护作用

Objective To investigate the protective effect of somatostatin (SS)combined with growth hormone (GH) in treatment of intestinal mucosal barrier injury in rabbits with severe acute pancreatitis (SAP), as well as its clinical significance. Methods Seventy-two rabbits were equally assigned into model group (SAP group), SS treated group (SS group) and SS combined with GH treated group (SS + GH group). SAP models were induced by retro-injection of 5% sodium taurocholate into the pancreatic duct. After modeling, all rabbits were given 5 % glucose saline daily.The rabbits in SS group and SS+GH group were continuously Given SS (3.5μg·kg-1·h-1)for 48 hours. Besides, the rabbits in SS+GH group were subcutaneously injected with 0.15 IU/kg of GH at the 1st and the 24th hours after modeling. The levels of serum amylase, serum tumor necrosis factor-α (TNF-α) and plasma diamine oxidase were measured at the 6th, 12th, 24th and 48th hours after modeling. The pathological changes of pancreatic tissue and ileal mucosa were observed. Survival rate was calculated. Data were analyzed using SPSS 16.0 software. The univariate analysis was used to compare the difference among groups. Results In SS+GH group, the levels of serum TNF-α and plasma diamine oxidase were (2. 43 ± 0. 14) pg/ml and (4. 61 ± 0. 45) U/L at the 24th hour respectively, and were (2.08±0.23) pg/ml and (3.75±0.47) U/L at the 48th hour, respectively,which were lower than those in SAP group and SS group [(2.80 0.30) pg/ml and (8.74 ± 1.77)U/L, respectively, at the 24th hour; (2. 45±0.12) pg/ml and (5. 02±0.95) U/L, respectively, at the 48th hour)]with significant difference (P＜0.05). The inflammation in pancreas and ileal mucosa was alleviated, and the integrity of bowel mucosa was improved. Survival rate of SS+GH group was significantly higher than SAP group and SS group. There was no significant difference in level of serum amylase between SS+GH group and SS group. Conclusion The combination of SS with GH may enhance the function of intestinal mucosa barrier and improve the prognosis of SAP in rabbits.     

细胞凋亡在急性坏死型胰腺炎早期肠黏膜上皮细胞死亡中的作用

目的观察急性坏死型胰腺炎(ANP)大鼠早期肠黏膜上皮细胞凋亡的发生及其演变规律,探讨其在肠黏膜屏障功能障碍中的作用.方法Spraque-Dawley大鼠48只,采用胆胰管内逆行注入5%牛磺胆酸钠溶液诱导大鼠ANP模型.假手术组(shamoperation,SO)大鼠仅作剖腹术.术后3、6、12和24h分批处死大鼠,取末端回肠组织,分别应用DNA琼脂糖凝胶电泳,异硫氰基荧光素(FITC)结合的Annexin-V和碘化丙啶(PI)标记细胞作流式细胞仪(FCM)检测和免疫组化(TUNEL法)等技术,研究ANP大鼠肠黏膜上皮细胞凋亡.结果DNA琼脂糖凝胶电泳结果显示,SO组仅于12h出现"梯形(ladder)”条带;ANP大鼠,各时点均可见"梯形”条带.FCM检测结果表明,术后3、6、12和24hSO组肠黏膜上皮脱落细胞凋亡比例分别为(53.7±3.7)%、(27.6±6.0)%、(39.0±4.8)%和(29.0±11.3)%;ANP组分别为(50.3±11.3)%、(79.7±9.2)%、(47.8±17.3)%和(49.6±9.5)%,术后6h达峰值,且较SO组明显增高(P＜0.01),凋亡与坏死细胞(A/N)比值为27.7±17.9.TUNEL法显示,凋亡细胞呈细胞核固缩、断片状,术后3、6、12和24hSO组凋亡指数为6.2±2.4、7.5±1.7、10.5±0.9和5.3±0.8;ANP组为17.5±3.5、20.4±2.9、14.8±1.7和14.2±2.1,各时点均较SO组明显增高(P＜0.01),且于术后6h达峰值.结论ANP大鼠早期肠黏膜上皮细胞凋亡为细胞死亡的主要模式;肠黏膜上皮细胞凋亡在ANP大鼠早期肠黏膜屏障功能障碍发生中可能起重要作用.