肠腔灌注高氧液对缺血-再灌注后肠黏膜屏障损伤的保护作用

目的探讨缺血期经肠腔灌注高氧液对家兔肠缺血-再灌注后肠黏膜屏障损伤的保护作用。方法健康家兔24只,随机均分成三组:缺血-再灌注组(I/R组)、高氧液处理组(HOS组)、假手术对照组(Sham组)。Sham组只开腹游离但不夹闭肠系膜上动脉(SMA),另两组用无损伤动脉夹夹闭SMA1h。HOS组于缺血期以20ml.kg-1.h-1恒速向肠腔灌注高氧液1h,I/R组则以相同的方式灌注等量的生理盐水,松开动脉夹再灌注2h后取标本。光镜下观察各组肠黏膜组织形态学改变,测定肠黏膜组织ATP含量和肠道的氧摄取率(ERO2);定量分析门静脉血中细菌内毒素(ET)含量;检测血清中肿瘤坏死因子α(TNF-α)、乳酸(Lac)水平;观察细菌移位率。结果与Sham组相比,I/R组光镜下肠黏膜损伤严重,肠黏膜组织ATP含量及肠道的ERO2均明显下降,血液中ET含量、Lac和TNF-α水平明显升高(P<0.05或P<0.01),同时出现了广泛的细菌移位;经肠腔灌注高氧液(HOS组)能够明显改善小肠黏膜损伤及上皮细胞形态学改变,显著提高肠黏膜组织ATP含量及ERO2;明显降低血液中ET、Lac和TNF-α水平(P<0.05或P<0.01),同时显著减少肠道细菌移位率(P<0.05)。结论肠腔灌注高氧液能够显著减轻肠缺血-再灌注引起的小肠黏膜屏障功能障碍,是一种安全有效的小肠保护方法。     

添加谷氨酰氨强化的早期肠内营养对肝移植大鼠肠屏障的保护作用

目的 观察使用添加谷氨酰胺(Gln)强化的早期肠内营养(EEN)对原位肝移植大鼠肠黏膜屏障的影响.方法 取Wistar大鼠,采用随机数字表法将大鼠分为对照组、肝移植组和EEN组.对照组仅手术分离肝十二指肠韧带;肝移植组和EEN组按两袖套法进行肝移植,供者为同批Wistar大鼠.术前3、2、1d及术后3h开始,给予EEN组受鼠添加了Gln(0.3 g·kg-1 ·d-1)的肠内营养混悬液(125 ml·kg-1 ·d-1)灌胃,肝移植组受鼠给予等体积生理盐水灌胃;对照组无特别处理.术后检测各组小鼠血浆内毒素、D-乳酸及血清肿瘤坏死因子α (TNF-α)的含量,测定肠黏膜TNF-αmRNA的表达,并对回肠肠壁组织进行超微结构观察.观察和记录各组小鼠的存活时间.结果 肝移植组和EEN组术后12、24和72 h的血浆内毒素、D-乳酸及血清TNF-α含量均明显高于对照组(P＜0.01),而EEN组术后24和72 h时较上述指标肝移植组均明显下降(P＜0.01).电镜下,对照组回肠黏膜上皮间隙正常,微绒毛排列整齐;术后12、24和72 h时,肝移植组小肠黏膜上皮间隙扩大,上皮细胞线粒体肿胀,微绒毛肿胀、空泡化,而EEN组超微结构的改变较肝移植组明显减轻.肝移植组和EEN组术后TNF-α mRNA表达明显升高(P＜0.01),而EEN组较同时点肝移植组的TNF-αmRNA表达明显下降(P＜0.01).对照组存活时间明显长于肝移植组和EEN组(P＜0.05),而EEN组存活时间较肝移植组明显延长(P＜0.05).结论 肝移植后可导致肠黏膜屏障损害,添加Gln强化的EEN对肝移植大鼠肠黏膜屏障具有明显的保护作用,可明显延长肝移植后大鼠的存活时间.     

The effect of N-acetylcysteine on oxidative stress in intestine and bacterial translocation after thermal injury

Ischemia due to transient splanchnic vasoconstriction following major burns causes oxidative and/or nitrosative damage in intestinal tissue followed by reperfusion injury. Thus, burn injury leads to breakdown in the intestinal mucosal barrier which can induce bacterial translocation (BT). As an antioxidant and anti-inflammatory agent the protective effects of N-acetylcysteine (NAC) are documented in several studies. This study was designed to determine the effect of NAC treatment on the oxidative stress in the intestine and BT after burn injury. To evaluate this, 32 Wistar rats were randomly divided into four groups as sham (n = 8), burn (n = 8), pre-burn, NAC injection (150 mg kg⁻¹, intraperitoneally) 15 min before thermal injury (n = 8), post-burn, NAC injection (150 mg kg⁻¹, intraperitoneally) 2 h after thermal injury. Under anesthesia, the shaved dorsal skin of rats was exposed to boiling water for 12 s to induce burn injury in a standardized manner. Twenty-four hours later, tissue samples from mesenteric lymph nodes (MLN), spleen, and liver were obtained under sterile conditions for microbiological analysis and ileum samples were harvested for biochemical analysis. In the burn group, the incidence of isolating bacteria in MLN, spleen, and liver specimens was significantly higher than other groups. NAC treatment prevented burn-induced BT in both pre- and post-burn groups. Thermal injury caused a significant decrease in glutathione (GSH) level, significant increases in malondialdehyde (MDA) and myeloperoxidase (MPO) activity at post-burn 24th hour. Treatment of rats with NAC significantly elevated the reduced GSH levels while decreasing MDA levels and MPO activity. These data suggested that NAC has a crucial cytoprotective role in intestinal mucosal barrier and preventive effects against burn injury-induced BT.     

Protective effect of glutamine-enriched early enteral nutrition on intestinal mucosal barrier injury after liver transplantation in rats

Background

The effect of glutamine-enriched early enteral nutrition (Gln-EEN) on intestinal mucosal barrier injury after liver transplantation (LT) remains uncertain.

Methods

The Wistar-to-Wistar rat LT model was used to explore the protective effect of Gln-EEN. Morphologic changes of intestinal mucosa, levels of intestinal malondialdehyde and secretory immunoglobulin (sIgA), plasma endotoxin, D-lactic acid, serum tumor necrosis factor-α (TNF-α), rates of bacterial translocation, and expression of intestinal nuclear factor-κB, TNF-α, and intercellular adhesion molecule-1 were determined.

Results

After LT, intestinal mucosa was damaged seriously. At 12, 24, and 48 hours posttransplantation, levels of intestinal sIgA were decreased; levels of malondialdehyde, endotoxin, D-lactic acid, and TNF-α, the ratio of bacterial translocation, and the expression of intestinal nuclear factor-κB, TNF-α, and intercellular adhesion molecule-1 all were increased. However, changes in earlier-mentioned parameters in recipients treated with Gln-EEN were attenuated remarkably at 24 to 48 hours.

Conclusions

Our data show that Gln-EEN is a potent protectant against intestinal mucosal barrier injury after LT.     

大鼠烫伤后肠道免疫屏障损伤的实验研究

为探索烧伤后肠道免疫屏障损伤的规律及其与肠道细菌移位的关系,我们对烫伤大鼠肠道免疫屏障的损伤进行了比较全面的动态观察,结果表明,伤后早期动物肠道内容物 IgA(免疫球蛋白 A)含量明显降低,肠固有层及上皮内 CD3 (T 细胞总数)和 CD4 (辅助/诱导 T 细胞)T 淋巴细胞明显减少,上皮内 CD4 与 CD8 (抑制/杀伤 T 细胞)T 细胞数量的比值倒置;伤后肠道细菌 IgA 包被率亦明显降低,且在整个实验过程中均明显低于伤前组;与上述改变相对应,肠道细菌移位率在伤后早期明显升高。提示,伤后肠道免疫屏障损伤是多方面的,而这一损伤对烧伤后肠道细菌移位和脓毒症的发生、发展可能起着重要作用。     

大鼠烫伤后肠道免疫屏障损伤的实验研究

为探索烧伤后肠道免疫屏障损伤的规律及其与肠道细菌移位的关系，我们对烫伤大鼠肠道免疫屏障的损伤进行了比较全面的动态观察，结果表明，伤后早期动物肠道内容物ＩｇＡ（免疫球蛋白Ａ）含量明显降低，肠固有层及上皮内ＣＤ３＋（Ｔ细胞总数）和ＣＤ４＋（辅助／诱导Ｔ细胞）Ｔ淋巴细胞明显减少，上皮内ＣＤ４＋与ＣＤ８＋（抑制／杀伤Ｔ细胞）Ｔ细胞数量的比值倒置；伤后肠道细菌ＩｇＡ包被率亦明显降低，且在整个实验过程中均明显低于伤前组；与上述改变相对应，肠道细菌移位率在伤后早期明显升高。提示，伤后肠道免疫屏障损伤是多方面的，而这一损伤对烧伤后肠道细菌移位和脓毒症的发生、发展可能起着重要作用。     

谷氨酰胺在重型颅脑损伤患者营养支持中的应用

目的研究谷氨酰胺强化营养治疗对重型颅脑损伤患者救治和营养支持巾的作用。方法对52例重型颅脑损伤患者分组进行谷氨酰胺强化营养治疗和常规营养治疗,测定其乳果糖排泄率和血浆内毒素水平并进行统计学处理,分析谷氨酰胺对脑外伤后肠黏膜屏障功能的影响,和在营养支持治疗中的作用。结果脑损伤患者早期内毒素水平明显升高,而在运用谷氨酰胺结合的肠内营养支持治疗下,其血浆内毒素水平要低于对照组,乳果糖排泄率明显较低。结论谷氨酰胺强化的营养支持能够保护肠粘膜屏障,并在颅脑损伤的救治中发挥作用。     

腹腔镜下氧化苦参碱腹腔灌洗对重症急性胰腺炎肠粘膜屏障损伤的作用

目的:探讨腹腔镜下氧化苦参碱(oxymatrine,OM)腹腔灌洗对重症急性胰腺炎(severe acute pancreatitis,SAP)的治疗作用及效果。方法:随机将20例SAP患者分为对照组(n=10)与OM灌洗组(n=10);两组均于腹腔镜下腹腔置管灌洗。对照组术后每12 h使用500 ml生理盐水灌洗腹腔,OM灌洗组术后每12 h应用500 ml OM溶液(200 mg OM)灌洗腹腔,分别于术前1 d(T0)及术后第1天(T1)、第2天(T2)、第3天(T3)抽取静脉血,测定血浆D-乳酸、内毒素浓度。结果:T0时,两组患者血浆D-乳酸浓度、血浆内毒素浓度相比差异无统计学意义(P>0.05);T1、T2、T3时,OM灌洗组血浆D-乳酸浓度、血浆内毒素浓度显著下降(P<0.05)。结论:腹腔镜下OM腹腔灌洗治疗SAP可减少、稀释腹腔渗出的大量炎性介质,且对肠黏膜屏障的损伤及细菌移位具有治疗作用。     

肝缺血-再灌注损伤对大鼠肠黏膜屏障功能及肠道菌群易位的影响

目的观察大鼠肝缺血-再灌注后肠黏膜屏障功能的变化,并探讨其对肠源性细菌移位的影响。方法64只成年健康雄性SD大鼠,随机分为对照组和实验组,每组32只。实验组用无创微血管钳于肝门部夹闭肝动脉、门静脉和胆总管,45 min后去除血管钳,分别在全肝血流阻断45 min后再灌注即刻(0 h)、再灌注1 h、再灌注2.5 h、再灌注4 h共4个时间点采集标本,测定血浆肿瘤坏死因子α(TNF-α)、D-乳酸水平以及肠黏膜中丙二醛、特异性分泌型免疫球蛋白(sIgA)的含量;观察回肠壁组织病理学改变,取肠系膜淋巴结(MLN)、肝、脾、肺、肾及回肠组织匀浆进行细菌培养和鉴定。对照组仅分离门静脉、肝动脉及胆总管,不行血管阻断。结果实验组在再灌注即刻及再灌注后血浆TNF-α的水平不断升高,再灌注后的TNF-α的水平明显高于再灌注即刻(P<0.05);D-乳酸的水平也明显高于对照组,但组内不同时间点比较,差异无统计学意义;肠黏膜中丙二醛的含量明显高于对照组(P<0.05),再灌注后的含量明显高于再灌注即刻(P<0.05);而sIgA在再灌注即刻及再灌注后明显低于对照组(P<0.05)。随着肝缺血-再灌注时间的延长,实验组肠黏膜的病理改变逐渐加重。实验组在再灌注即刻在MLN、肝、脾、肺及肾组织中可培养出细菌,随着再灌注后时间的延长,实验组中MLN、肝、脾、肺及肾组织中检出细菌的动物数明显增多(P<0.05),培养出的细菌与回肠的优势菌分布一致。结论肝缺血-再灌注损伤导致肠屏障功能损害,且引起肠道菌群易位。     

The effect of ethyl pyruvate on oxidative stress in intestine and bacterial translocation after thermal injury

BACKGROUND: Thermal injury causes a breakdown in the intestinal mucosal barrier due to ischemia reperfusion injury, which can induce bacterial translocation (BT), sepsis, and multiple organ failure in burn patients. The aim of this study was to investigate the effect of ethyl pyruvate (EP) on intestinal oxidant damage and BT in burn injury. MATERIALS AND METHODS: Thirty-two rats were randomly divided into four groups. The sham group was exposed to 21 degrees C water and injected intraperitoneal with saline (1 mL/100 g). The sham + EP group received EP (40 mg/kg) intraperitoneally 6 h after the sham procedure. The burn group was exposed to thermal injury and given intraperitoneal saline injection (1 mL/100 g). The burn + EP group received EP (40 mg/kg) intraperitoneally 6 h after thermal injury. Twenty-four hours later, tissue samples were obtained from mesenteric lymph nodes, spleen, and liver for microbiological analysis and ileum samples were harvested for biochemical analysis. RESULTS: Thermal injury caused severe BT in burn group. EP supplementation decreased BT in mesenteric lymph nodes and spleen in the burn + EP group compared with the burn group (P < 0.05). Also, burn caused BT in liver, but this finding was not statistically significant among all groups. Thermal injury caused a statistically significant increase in malondialdehyde and myeloperoxidase levels, and EP prevented this effects in the burn + EP group compared with the burn group (P < 0.05). CONCLUSION: Our data suggested that EP can inhibit the BT and myeloperoxidase and malondialdehyde production in intestine following thermal injury, suggesting anti-inflammatory and anti-oxidant properties of EP.     

大鼠烫伤后肠道细菌IgA包被率变化的动态观察

目的探讨导致烧伤后肠源性感染的免疫学因素。方法建立肠道细菌免疫球蛋白A(IgA)包被率的检测方法,对烫伤大鼠肠道细菌IgA包被率的变化和肠道细菌移位率的变化进行了动态观察。结果 40％体表面积烫伤后早期肠道细菌移位率明显升高,而后逐渐下降至伤前水平;各时相点肠道细菌的IgA包被率明显降低。结论烧伤后肠道免疫屏障受到损伤,伤后肠道内IgA保护功能的减弱可促使肠道细菌移位,与烧伤后脓毒症的发生、发展有密切关系。     

益生菌与核黄素联用对烫伤大鼠肠道屏障的保护作用

目的　观察益生菌与核黄素联合应用对烫伤大鼠细菌移位的防治效果 ,探讨其可能的作用机制。　方法　将Wistar大鼠随机分为烫伤对照组 (SC组 ,30只 )、烫伤治疗组 (ST组 ,30只 )、正常对照组 (NC组 ,10只 )。SC、ST组大鼠作 30 %ⅢTBSA度烫伤 ,ST组大鼠伤后立即向胃中灌注含双歧杆菌 5× 10 12 个集落形成单位 /L、蜡样芽孢杆菌 5× 10 10 个集落形成单位 /L和核黄素 5 0 0mg/L的等渗盐水混悬液 1.5ml,2次 /d。SC、NC组于相同时间灌注等量等渗盐水。观察细菌移位、肠道膜菌群、回肠分泌型免疫球蛋白A(SIgA)合成分泌及肠黏膜损伤修复等变化。　 结果　与SC组比较 ,ST组大鼠各脏器细菌移位率显著下降 (P =0.0 0 0～ 0.0 2 5),血浆内毒素水平在伤后 3d内降低显著 (P <0 0 5 ),回盲部膜菌群中双歧杆菌量升高 2 0～ 4 0倍 ,大肠杆菌和真菌量显著降低 ( P <0.0 1),致伤后 5d内黏膜损伤评分为 0～ 3(P <0.0 5),小肠黏液SIgA含量伤后 5d可恢复正常 ( P <0 0 1)。结论　益生菌与核黄素联合应用 ,可减轻烫伤大鼠细菌 /内毒素移位程度 ,有效保护肠道屏障     

大黄对严重烧伤患者胃肠动力及肠黏膜屏障的影响

目的 观察大黄对严重烧伤患者胃肠动力及肠黏膜屏障的影响.方法 选择太钢总医院2009年12月-2010年12月收治的30例严重烧伤患者,按随机数字表法分为对照组14例、治疗组16例.所有患者均于伤后48 h内入院,入院后6h内留置鼻胃管.治疗组患者入院后6h开始鼻饲大黄10 g,3次/d,并口服L-谷氨酰胺颗粒5 g,3次/d;入院后24 h开始进行肠内营养.对照组患者不使用大黄,其余各项营养支持治疗措施(口服L-谷氨酰胺颗粒、给予肠内营养)均与治疗组相同.观察2组患者用药后腹胀、对肠内营养的耐受、24 h肠鸣音恢复、排便等胃肠功能一般情况.于2组患者伤后3、7、14d清晨取静脉血分离血清,放射免疫法测定胃泌素水平,ELISA法测定胃动素水平,鲎试剂动态浊度法测定内毒素水平,酶学分光光度法测定二胺氧化酶活性.计数资料数据采用x2检验,计量资料数据采用t检验.结果 与对照组比较,治疗组患者的腹胀发生例数较少(x2=4 84,P =0.025),对肠内营养耐受例数及24 h肠鸣音恢复例数较多(x2=5.01,P=0 031;x2=4 84,P =0.028),排便时间明显提前,排便次数增加,大便较软.治疗组患者伤后3、7、14d血清胃泌素水平分别为(92±26)、(95±16)、(98±18) ng/L,均高于对照组[(80±15)、( 75±17)、(79 ±13) ng/L,t值分别为15.352、22.951、19.263,P值均小于0.01].治疗组伤后3、7、14 d血清胃动素水平分别为(246±80)、(299±76)、(300±1 00) ng/L,明显高于对照组[(189±44)、( 203±64)、(200±67) ng/L,t值各为14.173、19.294、26.298,P值均小于0 01].治疗组伤后3、7、14d血清内毒素水平分别为(0.398±0 035)、(0.373±0 005)、(0.238±0 019) EU/mL,均低于对照组[(0.493±0.043)、(0.501±0.045)、(0.423±0.099)EU/mL,t值分别为6 213、9.153、15.134,P＜0.05或P＜0.01].治疗组伤后3、7d血清二胺氧化酶活性分别为(3 0±0 4)、(2 9±0.5)U/mL,均低于对照组[(3 9±0 5)、(3 6±0.6)U/mL,t值分别3 982、4 236,P值均小于0.05];伤后14d2组水平接近(t =1.762,P＞0 05).结论 大黄能增加烧伤患者胃肠激素水平-促进其胃肠动力恢复,从而保护患者胃肠黏膜屏障功能.     

谷氨酰胺和生长激素对门静脉高压症术后营养状态和肠黏膜屏障的影响

目的 观察谷氨酰胺和生长激素联合肠外营养对肝硬化门静脉高压症手术患者术后营养状态和肠黏膜屏障的影响.方法 选择58例接受门静脉高压症手术的肝硬化患者,随机分为两组:实验组(添加谷氨酰胺和重组人生长激素,n=30)和标准营养组(对照组,n=28),两组术后第3天开始进行等氮等热量(每天125kJ/kg体重)营养支持,持续7d.术前、术后第3和第10天清晨分别抽取静脉血检测血清前白蛋白、转铁蛋白,并对手术前、后的尿乳果糖/甘露醇排泄率比值(L/M)、十二指肠黏膜绒毛高度、陷窝深度及肠黏膜增殖细胞核抗原(PCNA)指数进行对比.结果 实验组在术后第10天血清前白蛋白:(199.81±8.77)mg/L、转铁蛋白:(2.28±0.19)mg/L均显著高于对照组(P<0.05),L/M值升高小于对照组(P<0.05),肠黏膜绒毛高度(375.15±23.64)μm和陷窝深度(128.53±16.42)μm均大于对照组(P<0.05)及术前(P<0.05),肠黏膜上皮PCNA指数(24.27±4.25)大于对照组(P<0.05). 结论谷氨酰胺和生长激素联合肠外营养能够改善门静脉高压症手术后营养状态,降低小肠黏膜通透性,并维护肠黏膜形态学完整性,作用优于标准胃肠外营养.     

甲状腺激素对脓毒症大鼠肠粘膜屏障的保护作用

目的 探讨补充外源性甲状腺激素对脓毒症大鼠肠粘膜屏障的保护作用。方法 将ＳＤ大鼠３０只随机分为３组：假手术组、脓毒症组和治疗组。利用盲肠结扎打孔法（ＣＬＰ）制作大鼠脓毒症模型,通过腹腔注入１０ｍｇ／Ｌ三碘甲状腺原氨酸（Ｔ３）１．５ｍｌ／ｋｇ体重,以纠正脓毒症大鼠的低Ｔ３状态,用透射电镜观察肠粘膜机械性屏障的变化。结果 治疗组动物脓毒症表现轻,２４ｈ存活率显著高于脓毒症组（Ｐ〈０．０５）。脓毒症组大     

大鼠烫伤后肠道细菌IgA包被率变化的动态观察

目的探讨导致烧伤后肠源性感染的免疫学因素。方法建立肠道细菌免疫球蛋白Ａ（ＩｇＡ）包被率的检测方法，对烫伤大鼠肠道细菌ＩｇＡ包被率的变化和肠道细菌移位率的变化进行了动态观察。结果４０％体表面积烫伤后早期肠道细菌移位率明显升高，而后逐渐下降至伤前水平；各时相点肠道细菌的ＩｇＡ包被率明显降低。结论烧伤后肠道免疫屏障受到损伤，伤后肠道内ＩｇＡ保护功能的减弱可促使肠道细菌移位，与烧伤后脓毒症的发生、发展有密切关系。     

The role of thermal injury on intestinal bacterial translocation and the mitigating role of probiotics: A review of animal and human studies

IntroductionBurn patients represent a combination of nutritionally deplete and calorically demanding individuals who are susceptible to morbidity and mortality. A source of sepsis in thermal injury patients is the gastrointestinal tract with its interaction of normal and potentially pathogenic bacteria. The normal flora of the intestines maintains the equilibrium of the gut and prevents bacterial translocation (BT) through numerous mechanisms, all of which are disrupted as a consequence of thermal injury. Probiotic supplements with varying strains of bacteria have the potential to stabilize the integrity of the gut lining and decrease the incidence of BT after thermal injury.MethodsA literature review was conducted for animal and human studies in English addressing probiotic therapy in thermal injury. Keywords, “probiotics,” “thermal injury” and “burn” were utilized. Reference lists for each analyzed article were also examined to ensure completeness of literature search. Each article was reviewed for methodology, results and conclusions.ResultsEleven and six unique articles were identified addressing probiotics in thermal injury in animal and human studies, respectively. Heterogeneity between studies and limited demographic and outcome reporting prevented meta-analysis and comprehensive recommendations to be formalized.ConclusionWhile heterogeneity did not allow for meta-analysis, the results overall suggest a preventative, if not therapeutic, potential for probiotics in patients after thermal injury. Despite initial concern that probiotic therapy could lead to systemic infection in immune compromised individuals, this was not observed in the analyzed studies. Numerous unanswered questions exist in regards to optimizing probiotic therapy in patients after thermal injury.     

Specific inhibition of iNOS decreases the intestinal mucosal peroxynitrite level and improves the barrier function after thermal injury

Failure of GI tract mucosa to act as a barrier against bacterial translocation (BT) has been proposed as a potential source of sepsis and subsequent multiple organ failure post thermal injury. Nitric oxide (NO) is an inorganic radical produced by NO synthase (NOS) from -arginine. Gut mucosal constitutive NOS (cNOS) provides protection for itself. In contrast to cNOS, inducible NOS (iNOS) releases far greater amounts of NO, promotes oxidative reactions and is responsible for tissue injury. Peroxynitrite formed by the rapid reaction between superoxide and NO, is a toxic substance that contributes to tissue injury in a number of biological systems. This study was designed to investigate the effect of iNOS specific inhibitor S-methylisothiourea (SMT) on the postburn intestinal mucosal barrier function and the possible mechanism of SMT's action. Female SPF Sprague–Dawley rats underwent 35% total body surface area (TBSA) or sham burn. Either SMT or the same volume of saline was given (5 mg/kg, i.p. q 12 h) for 2 days to assess the effect of iNOS inhibition. On postburn day 2, the intestinal mucosal cNOS and iNOS activity were assayed by using Griess' reagent, the mesenteric lymph node (MLN), spleen and liver were collected and cultured for BT assay and the cellular localization of nitrotyrosine, a marker for peroxynitrite activity, was examined by immunostaining. After thermal injury in rats, administration of SMT for 2 days decreased the intestinal mucosal iNOS activity/tNOS activity ratio and the BT incidence. Nitrotyrosine immunostaining of the intestinal mucosa showed a decrease in the SMT-treated group. These findings suggest that SMT, a specific inhibitor for iNOS improves the barrier function after burn by suppression of the intestinal mucosal iNOS activity. The decrease in NO production resulted in decreased formation of peroxynitrite and subsequently decreased damage of mucosal tissue.     

缺血后处理对后肢挤压伤兔肠屏障的保护作用

目的 观察两种缺血后处理方式对后肢挤压伤兔肠道屏障的保护作用.方法 建立兔后肢挤压伤模型,并分别采取两种缺血后处理方式:交替夹闭-开放挤压伤侧髂总动静脉(I-post A,每次60 s,反复3次);交替捆绑-松弛挤压伤肢体近端(I-post B,每次60 s,反复3次).检测处理前、处理后2、6、12、24 h后血浆二胺氧化酶(DAO)及肠脂肪酸结合蛋白(iFABP)水平,24 h后取回肠组织苏木素-伊红(HE)染色观察肠黏膜形态学改变.结果 缺血后处理组在上述处理后4个时相点iFABP水平分别为I-post A:(108.75±4.81)、(117.04±3.70)、(125.52±4.22)、(109.12±6.95)μg/L,I-post B:(108.62±3.05)、(117.83±3.45)、(127.93±3.86)、(106.59±3.92)μg/L,均低于对照组(P＜0.05);处理后2、6 h血浆DAO水平分别为I-post A:(7.48±0.46)、(8.69±0.69)U/ml,I-post B:(7.43±0.46)、(8.70±0.70)U/ml,均低于对照组(P＜0.05);两缺血后处理模式组间差异无统计学意义(P＞0.05);各组肠黏膜在形态上未见明显差异.结论 缺血后处理对后肢挤压伤早期兔肠道屏障有保护作用,肠黏膜形态恢复早于肠屏障功能的修复.     

Administration of poly(ADP-ribose) polymerase inhibitor into bronchial artery attenuates pulmonary pathophysiology after smoke inhalation and burn in an ovine model

Poly(ADP-ribose) polymerase (PARP) is well known to be an enzyme that repairs damaged DNA and also induces cell death when overactivated. It has been reported that PARP plays a significant role in burn and smoke inhalation injury, and the pathophysiology is thought to be localized in the airway during early stages of activation. Therefore, we hypothesized that local inhibition of PARP in the airway by direct delivery of low dose PJ-34 [poly(ADP-ribose) polymerase inhibitor] into the bronchial artery would attenuate burn and smoke-induced acute lung injury.