创伤后血二胺氧化酶的变化与肠粘膜损伤

探讨创伤感染对肠道屏障功能的影响。以山羊、大鼠手术+失血再灌注+内毒素(LPS),大鼠肠缺血再灌注和犬低温枪伤多种创伤动物为模型,测定血浆二胺氧化酶(DAO)活性,并测定血乳酶、TNF和LPS含量。观察小肠病理形态改变。结果:失血再灌注后血浆DAO水平显著升高,给予内毒素后山羊血DAO水平再度升高。血浆DAO的变化与血乳酸,TNF和LPS变化呈高度相关(r=0.872,0.842和0.817,p<0.01)。光、电镜检查表明肠粘膜损伤,失血再灌注损伤可致肠粘膜屏障功能损伤,测定血浆DAO活性变化对判断小肠粘膜损伤有帮助     

大黄酸调节AMPK/mTOR信号通路对急性胰腺炎大鼠肠道菌群失调和肠屏障损伤的影响

目的 探讨大黄酸调节腺苷酸激活蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路对急性胰腺炎（AP）大鼠肠道菌群失调和肠屏障损伤的影响。方法 SPF级雄性7周龄SD大鼠50只,随机取10只作为假手术组,其余大鼠注射牛磺胆酸钠构建AP大鼠模型,将AP大鼠随机分为模型组、大黄酸组（100 mg/kg）、二甲双胍组（200 mg/kg）、大黄酸+二甲双胍组（100 mg/kg大黄酸+200 mg/kg二甲双胍）,每组10只,每天1次,连续注射2周。模型组和假手术组大鼠给予等量生理盐水。ELISA法检测血清DAO活性、TNF-α和IL-6水平;H&E染色检测胰腺和结肠组织病理学变化;进行粪便16S rRNA基因测序;Western Blot检测结肠屏障相关蛋白及AMPK-mTOR通路相关蛋白表达。结果 与假手术组相比,模型组大鼠血清DAO活性、IL-6、TNF-α水平以及胰腺和结肠组织病理损伤评分、AMPK水平、mTOR蛋白水平、埃希菌属相对丰度均显著升高（均P<0.05）,Shannon指数、Simpson指数、Chao1指数以及乳杆菌、双歧杆菌相对丰度和ZO-1...     

右美托咪啶对肺缺血/再灌注诱发小鼠肾脏超微结构改变的影响

目的：评价右美托咪啶对小鼠肺缺血/再灌注诱发肾脏损伤的影响。方法：雄性健康SPF级C57BL/6J小鼠50只,体重20 g~24 g,8~10周龄,采用随机数字表法,将其分为5组（n=10）：假手术组（sham组）、肺缺血/再灌注损伤组（I/R组）、肺缺血/再灌注+生理盐水组（NS组）、右美托咪啶组（Dex组）、右美托咪啶+阿替美唑（Atip）（DA组）。采用小鼠在体左侧肺门夹闭30 min再灌注180 min方法制备肺缺血/再灌注损伤（I/R）模型。Dex组在肺门阻断前30 min腹腔注射右美托咪啶20 μg/kg,NS组为用同Dex组等体积的生理盐水替代Dex,DA组腹腔注射右美托咪啶（20 μg/kg）+阿替美唑（250 μg/kg）,其余处理同I/R组。再灌注结束后静脉取血ELISA法检测血浆中IL-1β和TNF-α浓度;取双肾组织,透射电镜下观察肾组织病理学结果。结果：与对照组相比,其余组血浆IL-1β和TNF-α浓度明显升高,肾组织病理学损伤明显加重;与I/R、NS、DA组相比,Dex组IL-1β和TNF-α浓度明显下降,差异有统计学意义（P<0.05）,且肾组织超微结构损伤有所减轻。结论：右美托咪啶预先给药可减轻小鼠肺缺血/再灌注诱发肾脏损伤,其机制可能与抑制炎性反应有关。     

马齿苋多糖对溃疡性结肠炎大鼠肠组织IL-6/STAT3及NF-κB的影响

目的：采用TNBS （2,4,6-三硝基苯磺酸）复制溃疡性结肠炎大鼠模型,探索马齿苋多糖对溃疡性结肠炎大鼠肠组织IL6/STAT3及NF-κB的影响,明确IL-6/STAT3信号通路与慢性炎症性肠病发病的关系,为慢性溃疡性结肠炎的治疗寻找新靶点。方法：将40只SD大鼠随机分为对照组、模型组、美沙拉嗪组和马齿苋组（n=10）。采用TNBS诱导复制结肠炎模型,造模成功后第3天开始灌胃给药：美沙拉嗪组剂量为每次10 mg/kg,每日1次,连续3周;马齿苋组给予马齿苋多糖,每次10 ml/kg,每日1次,连续3周;模型组和对照组大鼠给予等体积生理盐水灌胃,每日1次,连续3周。收集大鼠结肠内容物称重,干燥后再次称重,取结肠组织作病理切片。采用ELISA试剂盒检测血清IL-6、IL-1β、TNF-α和核转录因子-kappa B （NF-κB）含量;免疫组化染色法测定结肠髓过氧化物酶（MPO）;RT-PCR法检测信号转导和转录激活因子（STAT3）、IL-6的mRNA。结果：与模型组、美沙拉嗪组比较,马齿苋组大鼠排便状态明显改善,肠粘膜水肿减轻;血清IL-6、sIL-6Rα、gp130,肠组织MPO、NF-κB含量均降低（P<0.01）。与模型组比较,马齿苋组STAT3、IL-6mRNA的表达水平明显降低（P<0.01）。与对照组比较,上述指标无显著性差异（P>0.05）。结论：马齿苋多糖通过降低大鼠血清IL-6、sIL-6Rα、gp130含量及肠组织MPO、NF-κB水平,减轻sIL-6Rα与IL-6形成复合物所致的炎症反应;经IL-6/STAT3信号通路下调大鼠肠组织STAT3和IL-6的mRNA水平,从而抑制炎症的发生。     

纳米四君子汤对急性肝功能衰竭小鼠肠屏障功能的影响

目的探讨四君子汤常态制剂及纳米制剂对急性肝功能衰竭小鼠肠屏障功能的影响。方法 BALB/c小鼠经腹腔一次性注射D-GaIN/LPS,制备急性肝衰竭致肠屏障损伤模型,观察四君子汤常态制剂及其纳米制剂对肠道正常菌群,肠黏膜分泌型免疫球蛋白A（sIgA）含量,肠组织二胺氧化酶（DAO）活性及肝功能的影响。结果小鼠腹腔注射D-GaIN/LPS后,血清中ALT、AST活性显著提高（P〈0.01）;肠道内肠杆菌、肠球菌数量明显上升（P〈0.01）,乳酸杆菌、双歧杆菌数量明显下降（P〈0.05）;肠黏膜sIgA及肠组织DAO含量明显降低（P〈0.01）。治疗组上述指标均得到明显改善,与自然恢复组比较差异有统计学意义（P〈0.05,P〈0.01）;治疗组间比较四君子汤纳米制剂效果要好于常态制剂。结论急性肝功能衰竭时肠屏障明显受损,四君子汤常态制剂和纳米制剂均具有一定的保护作用,但纳米制剂效果优于常态制剂,且用药量小。     

血必净对大鼠急性肺损伤的保护作用

目的：研究血必净对急性肺损伤大鼠的保护作用。方法：60只Wistar大鼠随机分为正常组、模型组、地塞米松（10 mg/kg）组与血必净低、中、高剂量（5、10、15 ml/kg）组,每组10只。通过腹腔注射5 mg/kg内毒素建立大鼠急性肺损伤模型,模型成功4 h后腹腔注射给药,每天1次,连续7 d;正常对照组和ALI模型组静脉注射等体积的生理盐水。7 d后采集动脉血,检测动脉血氧分压（PaO₂）、血清丙二醛（MDA）浓度和超氧化物歧化酶（SOD）的活性;取肺组织,检测肺系数（LI）、左肺湿/干质量比（W/D）、肺含水率[（W-D）/W],检测肿瘤坏死因子-α（TNF-α）、白细胞介素-10（IL-10）和高迁移率族蛋白-1（HMGB1）蛋白的表达。结果：与正常对照组比较,模型组大鼠LI、W/D、（W-D）/W,TNF-α和HMGB1蛋白表达以及血清MDA含量升高,PaO₂,IL-10蛋白表达和血清SOD活性减弱,差异有统计学意义（P < 0.01）;与模型组比较,血必净低、中、高剂量组大鼠LI、W/D及（W-D）/W,TNF-α和HMGB1蛋白表达以及血清MDA含量降低,PaO₂,IL-10蛋白表达和血清SOD活性增强,差异有统计学意义（P < 0.01）,其中血必净高剂量组效果较好,与中、低剂量组比较,差异有统计学意义（P < 0.05,P < 0.05）。结论：血必净能减轻对内毒素诱导的急性肺损伤,其药理机制可能与下调TNF-α和HMGB1蛋白表达和血清MDA水平和上调IL-10蛋白表达和血清SOD活性有关,且以高剂量组效果较好。     

延龄草对LPS诱导大鼠肝损伤的保护作用及机制

目的：研究延龄草（TTM）对脂多糖（LPS）诱导大鼠氧化应激与肝损伤的保护作用。方法：SD大鼠60只,按体重随机分成TTM高、中、低剂量组、模型组、地塞米松磷酸钠（DEX）对照组及空白对照组（n=10）。TTM高、中及低剂量组按（8、4、2） g/（kg·d） TTM灌胃,模型组、DEX对照组及空白对照组灌胃等量蒸馏水,每隔5 d,TTM高、中、低剂量组、模型组、DEX对照组按1 mg/kg腹腔注射LPS,DEX对照组同时腹腔注射DEX（5 mg/kg）,空白对照组注射等量生理盐水。30 d后,测定大鼠胸腺指数、脾脏指数,对血清一氧化氮合酶（NOS）、超氧化物歧化酶（SOD）活性与一氧化氮（NO）、谷胱甘肽（GSH）、硫代巴比妥酸反应产物（TBARS）、白细胞介素6（IL-6）、IL-10及肿瘤坏死因子α（TNF-α）含量,肝组织SOD、谷胱甘肽过氧化氢酶（GSH-Px）活性与GSH、TBARS含量进行检测。结果：与模型组相比,TTM高剂量组在（19~30） d体重显著降低（P<0.05）,TTM高、中、低剂量组胸腺指数,TTM高剂量组脾脏指数显著降低（P<0.05）,TTM高、中、低剂量组血清NOS活性与TBARS、NO含量显著降低（P<0.05）,TTM高剂量组血清SOD活性及中、高剂量组GSH含量显著上升（P<0.05）,TTM高、中剂量组血清IL-6、TNF-α含量显著降低,IL-10含量显著升高（P<0.05）,TTM中、高剂量组肝脏TBARS含量显著降低,TTM各剂量组肝脏SOD活性与中、高剂量组GSH-Px活性,高剂量组GSH含量显著升高（P<0.05）。结论：TTM对LPS所致大鼠的胸腺、脾脏萎缩有一定的延缓作用,能有效降低血清中NOS活性,减少NO生成,提升SOD、GSH-Px活性与GSH含量,减轻脂质过氧化,降低IL-6、TNF-α过量分泌、提升IL-10含量,有抗炎护肝的功能。     

布地奈德通过干预线粒体钙单转运蛋白影响哮喘大鼠气道上皮细胞自噬和屏障功能的机制

摘要 目的：探究布地奈德通过干预线粒体钙单转运蛋白影响哮喘大鼠气道上皮细胞自噬和屏障功能的机制。方法：30只雄性SD大鼠作为研究对象,并根据实验目的分为3组：对照组（正常大鼠,生理盐水干预,n=10）,哮喘组（通过OVA诱导大鼠哮喘模型,n=10）,布地奈德组（气雾剂布地奈德用于治疗过敏性哮喘的大鼠,n=10）。通过钙测定试剂盒和蛋白印迹分析大鼠气道上皮细胞中Ca²⁺的吸收和MCU蛋白表达;TEER和TRITC 荧光分析检测大鼠气道上皮中的屏障功能;免疫组化分析分气道上皮细胞屏障功能相关因子ZO-1、E-cadherin的蛋白表达;ELISAF分析BALF上清液中炎性因子IL-4、IL-5和IL-13的水平;二氢乙锭衍生物和蛋白印迹分析BALF中ROS含量和caspase-3活性。结果：哮喘组较对照组Ca²⁺浓度降低,MCU蛋白表达升高（P<0.05）,布地奈德组较哮喘组Ca²⁺浓度升高,MCU蛋白表达降低（P<0.05）。哮喘组较对照组TEER降低,TRITC升高（P<0.05）,布地奈德组较哮喘组TEER升高,TRITC降低（P<0.05）。哮喘组较对照组ZO-1、E-cadherin的蛋白表达降低（P<0.05）,布地奈德组较哮喘组ZO-1、E-cadherin的蛋白表达升高（P<0.05）。哮喘组较对照组IL-4、IL-5和IL-13的水平升高（P<0.05）,布地奈德组较哮喘组IL-4、IL-5和IL-13的水平降低（P<0.05）。对照组组支气管和肺泡结构未见异常,与对照组相比哮喘组大鼠表现出肺泡间隔增厚,可见的肺毛细血管水肿,以及肺毛细血管和肺泡间隙中的大量炎性细胞浸润（P<0.05）,与哮喘组相比,布地奈德组显著减轻肺部病变的严重程度（P<0.05）。哮喘组较对照组LC3B II/I、ATG5、Beclin-1 和LC3II 的表达升高（P<0.05）,布地奈德组较哮喘组LC3B II/I、ATG5、Beclin-1 和LC3II 的表达降低（P<0.05）。哮喘组较对照组ROS含量和caspase-3活性升高（P<0.05）,布地奈德组较哮喘组ROS含量和caspase-3活性降低（P<0.05）。结论：布地奈德通过调节MCU表达介导气道上皮细胞的屏障完整性和自噬水平,缓解哮喘气道炎症,改善哮喘症状。     

模拟100 m氦氮氧常规潜水对家兔氧化应激和炎性反应的影响

目的：探讨模拟100 m氦氮氧（Trimix）常规潜水对家兔氧化应激和炎性反应的影响。方法：空白组家兔8只,模拟100 m Trimix;常规潜水组家兔8只。模拟潜水按照Haldane理论计算所得的水下阶段减压表减压。Elisa法检测家兔模拟潜水前、后血清超氧化物歧化酶（SOD）、谷胱甘肽（GSH）、过氧化氢酶（CAT）、丙二醛（MDA）和过氧化脂质（LPO）等氧化/抗氧化指标的变化。同样采用Elisa法检测空白组和潜水组家兔肺、脑组织γ干扰素（IFN-γ）、肿瘤坏死因子-α（TNF-α）、白介素6（IL-6）、白介素8（IL-8）、髓过氧化物酶活力（MPO）和基质金属蛋白酶9（MMP-9）等炎性因子的表达,并比较组织湿干比（Wet/Dry ratio）。结果：家兔潜水后SOD和GSH活性明显降低（P<0.01）,CAT、MDA和LPO含量明显升高（P<0.01）;潜水组家兔肺、脑组织中IL-8、IL-6、IFN-γ、TNF-α、MMP-9和MPO的表达均较空白组显著升高（P<0.05,P<0.01）;潜水组家兔肺、脑组织湿干比与空白组差异不显著。结论：模拟100 m Trimix常规潜水对家兔氧化应激和炎性反应有显著影响。     

参麦注射液对严重烫伤大鼠肠道屏障功能的保护作用

目的:探索参麦注射液对30% Ⅲ°烫伤早期肠道屏障功能的保护作用,为参麦注射液防治肠源性感染提供实验依据。方法:Wistar大鼠60只,随机分为正常对照组、模型对照组,地塞米松5 mg/kg组、参麦注射液5、10、15 mg/kg组,每组10只,使用烫伤仪建立30% Ⅲ°烫伤动物模型,立即腹腔注射相应的药物,每天1次。烫伤72 h后,检测肝脏、脾脏、肠系膜淋巴结细菌移位量、血浆内毒素、二胺氧化酶(DAO)、肿瘤坏死因子-α(TNF-α)及白细胞介素-6(IL-6)水平和肠粘膜分泌型免疫球蛋白A(sIgA)的水平。结果:与正常对照组比较,模型组肝脏、脾脏、肠系膜淋巴结细菌移位量,血浆内毒素、DAO、TNF-α及 IL-6和肠黏膜sIgA水平明显升高(P＜0.01);与模型组比较,地塞米松组和参麦注射液5、10、15 mg/kg组肝脏、脾脏、肠系膜淋巴结细菌移位量,血浆内毒素、DAO、TNF-α及 IL-6和肠黏膜sIgA水平明显降低(P＜0.05或P＜0.01)。结论:参麦注射液可减轻严重烫伤引起的肠粘膜损伤,效果与地塞米松相当,高剂量组效果更好。     

胰高血糖素样肽-2对小鼠小肠缺血/再灌注损伤的保护作用

目的:观察胰高血糖素样肽-2(GLP-2)对缺血/再灌注损伤小鼠小肠的保护效应.方法:采用肠缺血/再灌注(I/R)模型,将32只小鼠随机分为4组(n=8)假手术(Sham)组、I/R组、I/R GLP-2保护组和I/R 谷氨酰胺(GLN)阳性对照组.光镜观察小肠黏膜形态学改变.检测小肠绒毛高度和隐窝深度;小肠组织二胺氧化酶(DAO)活性;肠系膜淋巴结(MLN)细菌易位率.结果:与假手术组相比,I/R组部分小肠绒毛坏死脱落,绒毛高度下降,隐窝变浅(P＜0 01);小肠组织DAO活性降低(P＜0.01);MLN细菌易位率增加(P＜0.05).与I/R组比,GLP-2组肠绒毛损害明显减轻,DAO活性回升(P＜0.01),细菌易位率回降(P＜0.05).结论:GLP-2对缺血/再灌注损伤小鼠小肠的形态结构及肠屏障功能具有保护作用.     

Abdominal paracentesis drainage attenuates intestinal mucosal barrier damage through macrophage polarization in severe acute pancreatitis

Abdominal paracentesis drainage (APD), as an effective treatment of severe acute pancreatitis (SAP) in clinical settings, can ameliorate intestinal barrier damage and the overall severity of SAP. However, the mechanism underlying therapeutic effects of APD on damaged intestinal mucosal barrier during SAP is still unclear. Here, SAP was induced by injecting 5% Na-taurocholate retrograde into the biliopancreatic duct of rats to confirm the benefits of APD on enteral injury of SAP and further explore the possible mechanism. Abdominal catheter was placed after SAP was induced in APD group. As control group, the sham group received no operation except abdominal opening and closure. By comparing changes among control group, sham group, and APD group, APD treatment obviously lowered the intestinal damage and reduced the permeation of intestinal mucosal barrier, which was evidenced by intestinal H&E staining, enteral expression of tight junction proteins, intestinal apoptosis measurement and detection of serum diamine oxidase, intestinal fatty acid binding protein and D-lactic acid. Furthermore, we found that APD polarized intestinal macrophages toward M2 phenotype by the determination of immunofluorescence and western blotting, and this accounts for the benefits of APD for intestinal injury in SAP. Importantly, the protective effect against intestinal injury by APD treatment was mediated through the inhibited ASK1/JNK pathway. In summary, APD improved the intestinal mucosal barrier damage in rats with SAP through an increasing portion of M2 phenotype macrophages in intestine via inhibiting ASK1/JNK pathway.     

烧伤后回肠组织二胺氧化酶活性变化的动态观察

采用大鼠烫伤模型对烧伤后回肠组织二胺氧化酶 (DAO)活性和肠道内容物IgA水平的变化进行动态观察。探讨烧伤后肠道机械屏障与肠道免疫屏障变化及相互间的关系。结果表明 ,烧伤后回肠DAO活性和肠道内IgA含量均明显降低 ,但二者变化趋势有所不同。提示烧伤后肠道屏障损伤与肠源性脓毒症关系密切 ,而且肠道机械屏障损伤较重 ,持续时间较长。     

Sendai virus-based liposomes enable targeted cytosolic delivery of nanoparticles in brain tumor-derived cells

Background

Nanogold has been investigated in a wide variety of biomedical applications because of the anti-inflammatory properties. The purpose of this study was to evaluate the effects of TPU (Therapeutic Pulsed Ultrasound) with gold nanoparticles (GNP) on oxidative stress parameters and the expression of pro-inflammatory molecules after traumatic muscle injury.

Materials and methods

Animals were divided in nine groups: sham (uninjured muscle); muscle injury without treatment; muscle injury + DMSO; muscle injury + GNP; muscle injury + DMSO + GNP; muscle injury + TPU; muscle injury + TPU + DMSO; muscle injury + TPU + GNP; muscle injury + TPU + DMSO + GNP. The ROS production was determined by concentration of superoxide anion, modulation of antioxidant defenses was determined by the activity of superoxide dismutase, catalase and glutathione peroxidase enzymes, oxidative damage determined by formation of thiobarbituric acid-reactive substance and protein carbonyls. The levels of interleukin-1?? (IL-1??) and tumor necrosis factor-?? (TNF-??) were measured as inflammatory parameters.

Results

Compared to muscle injury without treatment group, the muscle injury + TPU + DMSO + GNP gel group promoted a significant decrease in superoxide anion production and lipid peroxidation levels (p < 0.050). It also showed a significant decrease in TNF-?? and IL-1?? levels (p < 0.050) when compared to muscle injury without treatment group.

Conclusions

Our results suggest that TPU + DMSO + GNP gel presents beneficial effects on the muscular healing process, inducing a reduction in the production of ROS and also the expression of pro-inflammatory molecules.     

非酒精性脂肪性肝炎患者肠道菌群失调与肠道通透性及血清内毒素的相关性研究

目的 探讨非酒精性脂肪性肝炎患者肠道菌群失调与肠道通透性及血清内毒素的相关性.方法 选择肠道菌群中具有代表性的细菌共8种进行培养.研究对象为健康成人(A组)和非酒精性脂肪性肝炎(B组)各30例,计数两组肠道菌群中8种细菌的数量,检测所有被研究者的血清内毒素、二胺氧化酶(DAO)、D-乳酸及TNF-α的浓度,比较两组细菌数量和血清指标的变化,并进行相关分析.结果 与A组比较,B组双歧杆菌、乳杆菌和拟杆菌的菌落数显著减少(P＜0.01或P＜0.05),而肠球菌、肠杆菌的菌落数则有显著增加(P＜0.01或P＜0.05);酵母真菌、葡萄球菌、梭菌菌落数没有发生显著改变(P＞0.05);血清内毒素、DAO、D-乳酸、TNF-α水平显著增高(P＜0.01);相关分析显示肠杆菌与内毒素、DAO、D-乳酸相关(r=0.644,P＜0.001;r=0.415,P=0.023;r =0.383,P=0.037);血清内毒素和DAO、D-乳酸、TNF-α显著相关(r=0.485,P=0.007;r=0.477,P=0.008;r=0.490,P=0.006);TNF-α则与DAO、D-乳酸相关(r=0.426,P =0.019;r =0.440,P=0.015).结论 非酒精性脂肪性肝炎患者存在肠道菌群失调、肠道通透性增高及肠源性内毒素血症,肠杆菌的过度生长与肠源性内毒素血症及肠道通透性密切相关.     

Antinociceptive and anti-inflammatory effects of electroacupuncture on experimental arthritis of the rat temporomandibular joint

This study investigated the antinociceptive and anti-inflammatory effects of electroacupuncture (EA) on zymosan-induced acute arthritis of the rat temporomandibular joint (TMJ). Male Wistar rats were injected with saline or zymosan (control group; 2?mg) into the left TMJ. Low frequency EA (10?Hz, 30?min) was performed at acupoints (LI4, LI11, ST36, ST44) or sham points 2?h after or 1?h before zymosan administration. Mechanical hypernociception was accessed by the electronic Von Frey method after zymosan administration. Rats were sacrificed 6?h after zymosan administration and the joint was removed for histopathological analysis, myeloperoxidase activity assessment, vascular permeability observations, and immunohistochemical verification of inflammatory mediators. The results showed that EA inhibited zymosan-induced hypernociception, compared with the control group and with the sham group (p?< 0.05). The results showed that EA inhibited inflammatory parameters such as neutrophil migration, vascular permeability, and tumour necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression in the TMJ compared with the sham group (p < 0.05). Histopathological analysis showed that EA significantly inhibited edema and periarticular infiltration (p?< 0.05) compared with the control and sham groups. EA at acupoints produced antinociceptive and anti-inflammatory effects on zymosan-induced arthritis in the rat TMJ.     

Vasoactive intestinal peptide promotes gut barrier function against severe acute pancreatitis

To explore the influence of vasoactive intestinal peptide (VIP) on the gut barrier function in severe acute pancreatitis (SAP). Fifty four SD rats were randomly divided into three groups: sham operated (SO) group, SAP group and VIP intervention group. Each group was further divided into three time points: 1, 6 and 12 h after operation with 6 rats for each treatment point. SAP models were induced by retrograde injection of 4% sodium taurocholate into the bili-pancreatic duct. VIP intervention group was made by 5 nmol VIP intraperitoneal injection within 5 min after SAP model successfully obtained. The VIP in plasma and intestinal homogenate were detected with ELISA. The endotoxin in plasma of all groups was also tested. The expression levels of TLR4, TNF-α, IL-6, and IL-10 in gut mucosa were measured by RT-PCR. Meanwhile intestinal samples were harvested for pathological examination. Compared to SO group, the VIP in plasma and intestinal homogenate of SAP group were significantly decreased at 1 h after induction, and then gradually increased to beyond the level of SO group at 12 h. The endotoxin of SAP group was continually increased. The mRNA levels of TLR4, TNF-α, IL-6, and IL-10 were also increased with obvious pathological injuries in the intestine. In the VIP group, endotoxin in plasma was obviously decreased compared to SAP group. The expressions of TNF-α, IL-6 mRNA were suppressed while IL-10mRNA was increased. The intestinal pathological injuries were also markedly alleviated. These results suggested that VIP had protective effects on SAP gut barrier function through inhibiting intestinal mucosal inflammatory responses.     

Orexigenic hormone ghrelin attenuates local and remote organ injury after intestinal ischemia-reperfusion

Background

Gut ischemia/reperfusion (I/R) injury is a serious condition in intensive care patients. Activation of immune cells adjacent to the huge endothelial cell surface area of the intestinal microvasculature produces initially local and then systemic inflammatory responses. Stimulation of the vagus nerve can rapidly attenuate systemic inflammatory responses through inhibiting the activation of macrophages and endothelial cells. Ghrelin, a novel orexigenic hormone, is produced predominately in the gastrointestinal system. Ghrelin receptors are expressed at a high density in the dorsal vagal complex of the brain stem. In this study, we investigated the regulation of the cholinergic anti-inflammatory pathway by the novel gastrointestinal hormone, ghrelin, after gut I/R.

Methods and Findings

Gut ischemia was induced by placing a microvascular clip across the superior mesenteric artery for 90 min in male adult rats. Our results showed that ghrelin levels were significantly reduced after gut I/R and that ghrelin administration inhibited pro-inflammatory cytokine release, reduced neutrophil infiltration, ameliorated intestinal barrier dysfunction, attenuated organ injury, and improved survival after gut I/R. Administration of a specific ghrelin receptor antagonist worsened gut I/R-induced organ injury and mortality. To determine whether ghrelin''s beneficial effects after gut I/R require the intact vagus nerve, vagotomy was performed in sham and gut I/R animals immediately prior to the induction of gut ischemia. Our result showed that vagotomy completely eliminated ghrelin''s beneficial effect after gut I/R. To further confirm that ghrelin''s beneficial effects after gut I/R are mediated through the central nervous system, intracerebroventricular administration of ghrelin was performed at the beginning of reperfusion after 90-min gut ischemia. Our result showed that intracerebroventricular injection of ghrelin also protected the rats from gut I/R injury.

Conclusions

These findings suggest that ghrelin attenuates excessive inflammation and reduces organ injury after gut I/R through activation of the cholinergic anti-inflammatory pathway.     

Inhibition of long myosin light-chain kinase activation alleviates intestinal damage after binge ethanol exposure and burn injury

Laboratory evidence suggests that intestinal permeability is elevated following either binge ethanol exposure or burn injury alone, and this barrier dysfunction is further perturbed when these insults are combined. We and others have previously reported a rise in both systemic and local proinflammatory cytokine production in mice after the combined insult. Knowing that long myosin light-chain kinase (MLCK) is important for epithelial barrier maintenance and can be activated by proinflammatory cytokines, we examined whether inhibition of MLCK alleviated detrimental intestinal responses seen after ethanol exposure and burn injury. To accomplish this, mice were given vehicle or a single binge ethanol exposure followed by a sham or dorsal scald burn injury. Following injury, one group of mice received membrane permeant inhibitor of MLCK (PIK). At 6 and 24 h postinjury, bacterial translocation and intestinal levels of proinflammatory cytokines were measured, and changes in tight junction protein localization and total intestinal morphology were analyzed. Elevated morphological damage, ileal IL-1β and IL-6 levels, and bacterial translocation were seen in mice exposed to ethanol and burn injury relative to either insult alone. This increase was not seen in mice receiving PIK after injury. Ethanol-exposed and burn-injured mice had reduced zonula occludens protein-1 and occludin localization to the tight junction relative to sham-injured mice. However, the observed changes in junctional complexes were not seen in our PIK-treated mice following the combined insult. These data suggest that MLCK activity may promote morphological and inflammatory responses in the ileum following ethanol exposure and burn injury.