帕瑞昔布钠对脓毒症大鼠肠黏膜屏障功能的影响

目的 探讨帕瑞昔布钠对脓毒症大鼠肠屏障功能的影响。 方法 采用盲肠结扎穿孔法（cecal ligation and puncture, CLP）诱导脓毒症大鼠肠损伤模型。72只Wistar大鼠按随机数字表法分为4组（每组18只）：假手术组（Sham组）、假手术＋10 mg/kg帕瑞昔布钠组（SP组）、脓毒症组（CLP组）、脓毒症＋10 mg/kg帕瑞昔布钠组（CP组）。SP组和CP组大鼠于假手术或CLP后20 min腹腔注射帕瑞昔布钠10 mg/kg,12 h后再重复注射1次。CLP组和Sham组大鼠仅经腹腔注射等量生理盐水。于假手术或CLP后24 h,检测血浆二胺氧化酶（diamine oxidase, DAO）和D-乳酸的浓度,检测各组大鼠肠组织紧密连接蛋白（zonula occludens-1, ZO-1）和Claudin-1的蛋白表达,检测肠组织髓过氧化物酶（myeloperoxidase, MPO）的活性水平。光镜检测肠组织的病理学变化。 结果 与CLP组比较,CP组脓毒症大鼠血浆中DAO和D-乳酸水平降低（P〈0.05）,MPO活性下降（P〈0.05）,CP组肠组织ZO？蛳1和Claudin-1表达上调（P〈0.05）,CP组Chiu＇s评分降低（P〈0.05）。 结论 10 mg/kg帕瑞昔布钠治疗脓毒症大鼠能够减轻肠组织损伤和炎症反应,有效降低肠黏膜的通透性,改善肠屏障功能。     

类高血糖素多肽-2对大鼠梗阻性黄疸小肠上皮细胞紧密连接的调控

目的:探讨类高血糖素多肽-2(glucagon-like peptide-2,GLP-2)对梗阻性黄疸小肠上皮细胞紧密连接的调控机制.方法:建立梗阻性黄疸大鼠模型,于造模后10 d,将大鼠随机分为对照组和实验A、B组,另设正常进食大鼠作为正常组,每组10只.对照组给予0.01 mmol/L的PBS 0.5 mL,A组给予250g/(kg·d)、实验B组给予125 g/(kg·d)的GLP-2溶液0.5 mL皮下注射,2次/d,连续7 d后处死.取末端回肠黏膜组织,采用免疫组织化学及Western blots检测紧密连接蛋白ZO-1、Occludin、Claudin-1和Claudin-4的分布和表达,并利用图像分析系统对Western blots图像进行定量分析.结果:梗阻性黄疸时ZO-1和Occludin分布不均,染色变淡,线条模糊,边缘粗糙有毛刺状突起.补充外源性GLP-2后,A组的ZO-1、Occludin和Claudin-1染色有所恢复,且强阳性表达例数分别由对照组的2、3、2例升至A组的8、9、8例,差异有统计学意义(P均<0.05);Claudin-4表达和分布变化不明显.而B组对紧密连接蛋白没有影响.Western blot图像定量分析得到相同的结果.结论:梗阻性黄疸时补充外源性GLP-2,能够影响小肠黏膜上皮紧密连接蛋白的分布和表达,可以恢复肠黏膜上皮屏障的完整性.     

GLP-2对实验性梗阻性黄疸小肠上皮细胞紧密连接的调控

目的:探讨类高血糖素多肽-2（GLP-2）对实验性梗阻性黄疸小肠上皮细胞紧密连接的调控。方法:建立梗阻性黄疸大鼠模型，造模后10d随机分组，每组10只。黄疸组皮下注射0.01 mmol/LPBS 0.5 mL，实验甲组腹腔注射250 g/（kg·d），实验乙组腹腔注射125g/（kg·d）的GLP-2溶液0.5 mL，每天2次，连续7 d后处死。另设正常对照组，用免疫组化及Western blots检测末端回肠黏膜紧密连接蛋白ZO-1,Occludin及Claudin-1, Claudin-4的分布和表达，并用图像分析系统对Western blots图像进行定量分析。结果:正常情况下ZO-1,Occludin和Claudin-1染色强阳性率分别为70.0%,80.0%和70.0%。梗阻性黄疸时ZO-1和Occludin分布不均，染色变淡，线条模糊。补充外源性GLP-2后，实验甲组的ZO-1,Occludin和Claudin-1染色有所恢复，且强阳性表达率分别从黄疸组的20.0%，30.0%和20.0%升至实验甲组的80.0%,90.0%和80.0% (均P<0.05)；Claudin-4表达和分布变化不明显。实验乙组对紧密连接蛋白无影响。Western blots图像定量分析得到相同的结果。 结论:梗阻性黄疸时，补充GLP-2可影响小肠黏膜上皮紧密连接蛋白的分布和表达；提示GLP-2能恢复和维持小肠黏膜上皮屏障的完整性。     

不同营养方式对梗阻性黄疸大鼠肠紧密连接蛋白的影响

目的 观察肠内营养(EN)及肠外营养(PN)对阻塞性黄疸(OJ)大鼠小肠紧密连接蛋白的影响.方法 将50只Wistar大鼠随机分5组,EN组和PN组给予等热量等氮量营养.7 d后采用免疫组织化学和Western blot法检测各组末端回肠黏膜的闭锁小带-1(ZO-1)、闭锁蛋白(Occludin)与肌球蛋白轻链激酶(MLCK)的表达,并对Western blot图像进行定量分析.结果 正常回肠黏膜ZO-1和Occludin沿绒毛下方均匀连续分布,MLCK主要分布在细胞质内.阻黄时ZO-1、Occludin和MLCK分布散乱,染色稀疏.PN组的ZO-1、Occludin和MLCK的强阳性染色数由阻黄组的2、2、1例升至4、5、3例(P均>0.05),而EN组的强阳性染色数分别上升为7、6、5例(P均<0.05).通过对Western blot显影图像进行定量分析,EN组和PN组的ZO-1的灰度值较阻塞性黄疸组明显上升(均P<0.05);Occludin和MLCK的灰度值在EN组上升(P<0.05),PN组没有变化.结论 梗阻性黄疸时大鼠小肠黏膜上皮ZO-1、Occludin和MLCK分布紊乱,表达下降.肠内、外营养均能够恢复受损的紧密连接蛋白,肠内营养的作用更强.     

清胰颗粒对重症急性胰腺炎大鼠肠黏膜上皮紧密连接的保护作用

目的：探讨清胰颗粒对重症急性胰腺炎（SAP）大鼠肠黏膜上皮紧密连接的保护作用。方法：24只健康雄性Wistar大鼠随机分为假手术组、SAP组和清胰颗粒组。采用3.5%牛磺胆酸钠胆胰管逆行注射制备SAP大鼠模型,清胰颗粒组于造模前2 h、造模后6 h和18 h分别给予清胰颗粒灌胃,SAP组以同样的方法给予安慰剂。各组分别于造模后24 h取末端回肠,HE染色,光镜下观察病理组织学改变,采用Chiu’小肠组织损伤评价标准对肠黏膜损伤进行评价,应用Western blot和实时荧光定量PCR法检测回肠黏膜上皮紧密连接蛋白（Occludin）表达。结果：与假手术组相比,SAP组大鼠Chiu’小肠组织损伤评分（4.6±0.6） vs （0.0±0.0）明显升高,与SAP组相比,清胰颗粒组Chiu’小肠组织损伤评分（2.0±0.4）vs（4.6±0.6）明显降低;Western blot和实时荧光定量PCR结果显示,与假手术组相比SAP组大鼠Occludin蛋白表达（1.2±0.4）vs（3.2±0.4）和mRNA表达（1.3±0.3）vs（2.9±0.5）明显降低（P＜0.05）;与SAP组相比,清胰颗粒组 Occludin蛋白表达（4.1±0.4）vs（1.2±0.4）和mRNA表达（4.2±0.3）vs（1.3±0.3）明显升高（P＜0.05）。结论：清胰颗粒能减轻SAP大鼠肠黏膜损伤程度,这一作用可能与增强肠黏膜紧密连接蛋白Occludin表达有关。     

帕瑞昔布钠联合镇痛对乳腺癌患者术后炎症及应激反应的影响

目的探讨帕瑞昔布钠联合镇痛对乳腺癌患者术后炎症和应激反应的影响。方法择期在全麻下行乳腺癌根治术患者60例,随机分为帕瑞昔布钠联合镇痛组(P组)和对照组(C组),每组30例。两组术后均采用布托啡诺行自控静脉镇痛。分别于术毕即刻、术后12、24、36h静注帕瑞昔布钠40mg(P组)和生理盐水5ml(C组)。用放免法测定血浆前列腺素E2(PGE2)、肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6及肾素、血管紧张素-Ⅱ(ANG-Ⅱ)、醛固酮(ALD)、皮质醇(Cor)浓度。结果术后12～48h,P组血浆PGE2、TNF-α、IL-6及肾素、ANG-Ⅱ、ALD、Cor浓度无明显变化,但在术后12、24h明显低于C组(P<0.05)。结论帕瑞昔布钠联合布托啡诺镇痛可减轻乳腺癌根治术患者术后的炎症反应和应激反应,有一定的免疫保护作用。     

小肠缺血再灌注损伤恢复期骨形成蛋白-4促进肠黏膜屏障恢复的实验研究

目的探讨在小肠缺血再灌注(I/R)损伤恢复期时小肠上皮细胞中骨形成蛋白-4(BMP4)促进肠黏膜屏障功能恢复的机制。方法 28只6~8周龄C57BL/6J雄性小鼠,采取随机数字表法随机抽取24只小鼠用于I/R操作,余下4只小鼠进行假手术(SO)操作。I/R后分别于6、12、24、48 h时随机抽取4只小鼠处死用于观察小鼠小肠黏膜的形态学变化并检测其空肠上皮细胞中BMP4 mRNA表达的变化,另外8只小鼠分配用于肠黏膜损伤恢复期(根据预实验结果,选择I/R后24 h时作为观察时间点)的实验观察。对I/R后恢复期即I/R后24 h时的小鼠腹腔内分别注射浓度为30 ng/(m L·kg)的重组人BMP4蛋白(I/R-24 h-BMP4组)和生理盐水(I/R-24 h-NS组),对不注射任何液体的小鼠作为对照组(I/R-24 h-空白组),采用随机数字表法每组随机分配4只小鼠,然后检测各组小鼠空肠黏膜组织跨膜电阻抗(TER)的变化,同时采用Western blot法检测各组小鼠小肠上皮细胞中BMP4蛋白、紧密连接蛋白(occludin、ZO-1)、Notch信号通路蛋白(Notch1、Jagged1)及磷酸化Smad6蛋白(p-Smad6)的蛋白表达变化。结果在小鼠小肠I/R后24 h时,小肠黏膜绒毛上皮层损伤明显减轻、水肿减轻、肠绒毛少部分断裂、脱落。与SO小鼠比较,I/R后6、12、24、48 h时空肠上皮细胞中BMP4 mRNA表达呈逐渐增高趋势。小鼠I/R损伤后恢复期即I/R后24 h时发现,给予外源性BMP4蛋白刺激后,I/R-24 h-BMP4组空肠黏膜组织中TER值、BMP4、occludin、ZO-1、Notch1、Jagged1、p-Smad6蛋白表达均较I/R-24 h-NS组和I/R-24 h-空白组升高。结论从本研究初步研究结果看,在小肠I/R损伤后恢复期,空肠黏膜屏障通透性增大、BMP4表达增加,其可能是通过激活Notch信号通路(Notch1、Jagged1)和Smad经典信号通路(p-Smad6)与促进紧密连接蛋白(occludin和ZO-1)表达增加来促进肠黏膜屏障功能的恢复,从而减轻肠黏膜屏障功能损伤。     

梗阻性黄疸大鼠肠黏膜上皮紧密连接蛋白和MLCK的研究

目的:探讨梗阻性黄疸肠黏膜屏障破坏的机制。方法:建立梗阻性黄疸大鼠的动物模型,分别于胆管结扎10 d和20 d后，采用免疫组化、Western blot方法检测末端回肠黏膜的紧密连接蛋白成员ZO-1和Occludin与肌球蛋白轻链激酶（MLCK）的分布和表达。结果:正常回肠黏膜层ZO-1和Occludin的分布相似，主要位于上皮细胞的边缘，细胞膜顶端，沿绒毛下方均匀连续分布；MLCK主要分布在细胞浆内。梗阻性黄疸时ZO-1和Occludin分布不均, 染色变淡，线条模糊，边缘粗糙有毛刺状突起；MLCK分布散乱，染色稀疏。与对照组相比20 d组和10 d组的ZO-1，Occludin，MLCK数量明显减少，强阳性表达率分别从70.0 %，80.0 %，70.0 %降至10 d组的28.6 %，28.6 %，28.6 % (均P＜0.05)和20 d组的ZO-1从10 d 组的28.6 %降至14.3 %, 35.7 %, 21.4 % (均P＜0.05)。20 d 组的ZO-1下降较10 d组更为明显（P<0.05）, 而Occludin和MLCK变化不明显。Western blot检测的结果与之相似。结论:梗阻性黄疸时大鼠小肠黏膜上皮ZO-1，Occludin，MLCK分布紊乱，表达下降，小肠黏膜上皮屏障的完整性破坏。     

帕瑞昔布钠术前用药对乳腺切除术患者血清IL-6及术后镇痛的影响

目的观察帕瑞昔布钠术前用药对乳腺切除术患者血清IL-6及术后镇痛的影响。方法选择乳腺癌行乳腺切除手术患者60例,随机分为帕瑞昔布钠(P组)和对照组(C组),每组30例。所有患者均行静吸复合全身麻醉。P组于麻醉诱导前10min静注帕瑞昔布钠40mg,C组静注生理盐水5ml。术后两组均行静脉自控镇痛(PCIA)。记录术后2、4、8、12、24h的疼痛VAS评分。采用ELISA法测定诱导前10min、术后4、8和24h的血清IL-6浓度。结果术后2~12hP组VAS评分均明显低于C组(P0.05)。与诱导前10min比较,术后4~24h两组血清IL-6浓度均明显升高(P0.01),但P组明显低于C组(P0.01)。结论帕瑞昔布钠术前用药可改善乳腺切除术患者术后镇痛效果,减少血清IL-6的产生。     

瑞芬太尼对腹腔感染脓毒症小鼠肝肺组织诱导型一氧化氮合酶的影响

目的 观察瑞芬太尼对腹腔感染脓毒症小鼠肺组织和肝组织诱导型一氧化氮合酶(iNOS)的影响.方法 采用小鼠盲肠结扎穿孔术制备脓毒症模型,将40只雄性昆明小鼠随机分为假手术组(Sham组)、脓毒症组(CLP组)、瑞芬太尼治疗组(R1组)、瑞芬太尼对照组(R2组).Western blot方法检测肺组织和肝组织iNOS蛋白表达,双抗体夹心酶联免疫吸附法测定肝肺组织白细胞介素(IL)-10和IL-6水平,观察PaO_2、肺组织髓过氧化物酶(MPO)活性、血清ALT和AST活性及电镜下组织超微结构改变.结果 与Sham组比较,CLP组PaO_2显著降低,肺组织和肝组织中iNOS蛋白表达、肺组织MPO活性、ALT和AST活性显著增强(P<0.01),肺组织IL-6和IL-10水平显著增加为649.74±90.47和501.06±57.67(P<0.01),肝组织IL-6和IL-10水平显著增加为341.05±28.73和267.50±41.82,R2组以上指标均无明显变化;与CLP组比较,R1组PaO_2明显增加,iNOS蛋白表达,IL-6和IL-10水平、MPO活性、ALT和AST活性显著降低(P<0.01),电镜显示肺组织和肝组织损伤程度较CLP组略减轻.结论 瑞芬太尼对脓毒症感染致急性肺损伤和肝损伤有保护作用,其机制可能通过抑制iNOS蛋白的表达,降低炎性因子水平有关.     

大黄附子汤对重症急性胰腺炎早期大鼠肠黏膜机械屏障的影响及其意义

目的:观察大黄附子汤(DHFZT)对早期重症急性胰腺炎肠黏膜机械屏障的影响。方法:24只雄性SD大鼠采用随机数字表法分为4组：假手术(SH)组、假手术-DHFZT(SH-DHFZT)组、重症急性胰腺炎(SAP)组、DHFZT治疗(SAP-DHFZT)组,每组6只。SH组、SH-DHFZT组大鼠开腹后,翻动胰腺数次后关腹...     

Breakdown of intestinal mucosa via accelerated apoptosis increases intestinal permeability in experimental severe acute pancreatitis

BACKGROUND: Bacterial translocation plays an important role for infectious complications in severe acute pancreatitis (SAP). Breakdown of intestinal mucosal integrity may increase intestinal permeability and may be implicated in bacterial translocation. It is suggested that increase in intestinal permeability is correlated with the changes of tight junction and/or apoptosis in intestinal epithelial cells. The aim of this study was to investigate the changes of intestinal mucosa and its permeability in SAP. METHODS: SAP was induced by injection of 3% sodium deoxycholate into the biliopancreatic ducts in rats. Permeability of intestinal wall was assayed ex vivo by measuring the leaked amount of FITC-dextran from the ileum pouch. Alteration of tight junction proteins such as zonula occludens (ZO)-1 and Occludin was evaluated by Western blotting and immunofluorescence staining. Apoptotic change of intestinal mucosa was detected by TUNEL staining and DNA fragmentation ELISA. In vitro, apoptosis-inducing effect of pancreatitis-associated ascitic fluid (PAAF) was examined using T84 cells. Integrity of monolayer cells was assessed by transepithelial electric resistance (TEER). RESULTS: Permeability of ileum was significantly increased 6 h after induction of SAP. Blood endotoxin level was significantly elevated and bacterial translocation occurred 18 h after induction of SAP. Six hours after induction of SAP, expressions of ZO-1 and Occludin were not altered, but apoptosis of ileum mucosa was significantly accelerated. Addition of PAAF to T84 cells did not affect expressions of ZO-1 or Occludin, but significantly increased the apoptosis and significantly decreased TEER. CONCLUSIONS: These results suggest that breakdown of intestinal mucosa via accelerated apoptosis may increase in intestinal permeability in SAP and that PAAF contains factor(s) that accelerates the apoptosis of intestinal epithelial cells.     

bFGF ameliorates intestinal mucosal permeability and barrier function through tight junction proteins in burn injury rats

BackgroudTo investigate the protective effect of exogenous basic fibroblast growth factor (bFGF) treatment on the intestinal mucosa in scalded rats.MethodsThirty-six SD rats were randomly divided into 3 groups (n = 12): sham group, scald group and bFGF group (0.5 mg/kg). Intestinal barrier dysfunction was evaluated by permeability of intestinal mucosa to fluorescein isothiocyanate (FITC)-dextran and Chiu’s grading system. H&E staining was used to detect the morphological changes of intestinal mucosa. Immunohistochemistry was used to observe zonula occludens-1 (ZO-1) and occludin. Western blot assay was used to detect the expression of ZO-1, Claudin-1, occludin and myosin light-chain kinase (MLCK).ResultsThe results demonstrated that following bFGF treatment, permeability of the intestinal epithelium barrier of was significantly decreased compared to scald group. H&E staining and Chiu’s grading were consistent with previous result. The expression of ZO-1, Claudin-1, occludin in bFGF group were significantly increased compared to scald group, while MLCK protein was decreased.ConclusionsbFGF ameliorates permeability of intestinal mucosa after burns. The possible mechanism may be relate to bFGF could increase the expression level of tight junction proteins (TJPs).     

缺氧诱导因子1α介导单羧酸转运蛋白1表达参与短链脂肪酸对肠道缺氧保护作用的研究

目的 明确缺氧条件下缺氧诱导因子1α(HIF-1α)对肠上皮细胞单羧酸转运蛋白1(MCT-1)的表达调控,并初步探究短链脂肪酸(SCFAs)在缺氧条件下对肠屏障的保护作用。方法 取健康回肠组织及肠缺血坏死患者的回肠组织,进行免疫组织化学染色,检测肠上皮MCT-1表达情况。正常C57小鼠、肠上皮特异性HIF-1α敲除鼠(HIF-1α^ΔIEC)以及对照小鼠(HIF-1α^flox/flox)构建小肠缺血再灌注(I/R)损伤模型,随机分为假手术组(Sham组)、I/R组,I/R+丁酸组,取回肠末段的组织行免疫组织化学染色及肠液行SCFAs检测,透射电镜观察小鼠回肠超微结构变化。培养肠上皮细胞系Caco-2,建立缺氧模型,用Western blotting法分别检测常氧组、缺氧组、缺氧+siHIF-1α组、丁酸+缺氧组、siMCT-1+丁酸+缺氧组MCT-1、HIF-1α和肠上皮紧密连接蛋白Claudin1、Occludin的表达情况;跨上皮电阻(TER)测定评估各组肠上皮屏障功能变化。结果 与假手术组相比,I/R组肠道内SCFAs无明显变化。缺血、缺...     

金黄色葡萄球菌和纤维连接蛋白结合蛋白A对血管内皮细胞紧密连接的破坏作用

目的观察金黄色葡萄球菌和纤维连接蛋白结合蛋白A基因（fnBA）敲除金黄色葡萄球菌菌株对人微血管内皮细胞（HMEC-1）紧密连接蛋白ZO-1、Claudin-5的影响，并探讨金黄色葡萄球菌侵袭血管内皮细胞的机制。 方法将野生金黄色葡萄球菌菌株NCTC8325与HMEC-1按100︰1比例共培养，实时定量RT-PCR检测共培养30 min、60 min和120 min时HMEC-1紧密连接成份ZO-1和Claudin-5 mRNA的表达，同时应用Western blot分析和免疫组织化学染色观察共培养不同时间紧密连接蛋白ZO-1和Claudin-5的表达。构建fnBA基因敲除突变菌株NCTC8325ΔfnbA，以野生金黄色葡萄球菌菌株NCTC8325为阳性对照，观察突变株NCTC8325ΔfnbA与HMEC-1共培养120 min后紧密连接蛋白ZO-1和Claudin-5的变化。 结果金黄色葡萄球菌NCTC8325与HMEC-1共培养30 min、60 min和120 min后紧密连接蛋白ZO-1、Claudin-5 mRNA的表达在30 min、120 min时较对照组显著下降[30 min时与对照组比较：ZO-1：t = 4.104、P = 0.015，Claudin-5 mRNA：t = 2.802、P = 0.049；120 min时与对照组比较：ZO-1：t = 3.478、P = 0.025，Claudin-5 mRNA：t = 1.802、P = 0.261]，但60 min时ZO-1、Claudin-5 mRNA的表达有一过性升高。与金黄色葡萄球菌NCTC8325共培养后，免疫组织化学结果发现在30 min时ZO-1和Claudin-5两种紧密连接蛋白较对照组表达显著下降（t = 33.6、59.03，P均< 0.001），120 min时ZO-1和Claudin-5两种紧密连接蛋白较对照组表达亦显著下降（t = 31.8、60.75，P均< 0.001）；Western blot与免疫组组织化学结果一致。与突变菌株NCTC8325ΔfnbA共培养30 min、60 min和120 min后，在30 min和60 min时ZO-1、Claudin-5蛋白的表达与NCTC8325组差异无统计学意义（P均> 0.05），在120 min时ZO-1和Claudin-5蛋白的表达较NCTC8325组显著升高，差异均有统计学意义（ZO-1：t = 14.89、P < 0.001，Claudin-5：t = 7.008、P = 0.002）。 结论金黄色葡萄球菌能通过下调紧密连接蛋白破坏HMEC-1紧密连接屏障，且其表面蛋白FnBPA发挥了重要作用。     

Dexmedetomidine protects against burn-induced intestinal barrier injury via the MLCK/p-MLC signalling pathway

BackgroundEvidence suggests that sedative dexmedetomidine can prevent intestinal dysfunction. However, the specific mechanisms of its protective effects against burn-induced intestinal barrier injury remain unclear. We aimed to explore the possible positive effects of dexmedetomidine on burn-induced intestinal barrier injury and the effects the myosin light chain kinase (MLCK)/phosphorylated myosin light chain (p-MLC) signalling pathway in an experimental model of burn injury.MethodsIn this study, the plasma concentration of fluorescein isothiocyanate-labelled dextran (FITC-dextran) was measured. Histological changes were evaluated using haematoxylin and eosin (HE) staining. Tight junction proteins were evaluated by western blot and immunofluorescence analyses to assess the structural integrity of intestinal tight junctions. The level of inflammation was detected by enzyme-linked immunosorbent assay (ELISA).ResultsThe results shows that the increase in intestinal permeability caused by burn injury is accompanied by histological damage to the intestine, decreases in the expression of the tight junction proteins Zonula Occludens-1 (ZO-1) and Occludin, increases in inflammatory cytokine levels and elevation of both MLCK protein expression and MLC phosphorylation. After dexmedetomidine treatment, the burn-induced changes were ameliorated.ConclusionsIn conclusion, dexmedetomidine exerted an anti-inflammatory effect and protected tight junction complexes against burn‑induced intestinal barrier damage by inhibiting the MLCK/p-MLC signalling pathways.     

Vasoactive intestinal peptide decreases inflammation and tight junction disruption in experimental necrotizing enterocolitis

Background and PurposeExcessive inflammatory cell infiltration and accumulation in the intestinal mucosa are pathological features of necrotizing enterocolitis (NEC) leading to intestinal barrier disruption. Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent that regulates intestinal epithelial barrier homeostasis. We previously demonstrated that VIP-ergic neuron expression is decreased in experimental NEC ileum, and this may be associated with inflammation and barrier compromise. We hypothesize that exogenous VIP administration has a beneficial effect in NEC.MethodsNEC was induced in C57BL/6 mice by gavage feeding, hypoxia, and lipopolysaccharide administration between postnatal day (P) 5 and 9. There were four studied groups: Control (n = 6): Breast feeding without stress factors; Control + VIP (n = 5): Breast feeding + intraperitoneal VIP injection once a day from P5 to P9; NEC (n = 9): mice exposed to NEC induction; NEC + VIP (n = 9): NEC induction + intraperitoneal VIP injection. Terminal ileum was harvested on P9. NEC severity, intestinal inflammation, (IL-6 and TNFα), and Tight junctions (Claudin-3) were evaluated.ResultsNEC severity and intestinal inflammation were significantly decreased in NEC + VIP compared to NEC. Tight junction expression was significantly increased in NEC + VIP compared to NEC.ConclusionVIP administration has a beneficial therapeutic effect in NEC by reducing inflammation and tight junction disruption.