小肠缺血再灌注损伤与免疫细胞凋亡关系的研究进展

缺血再灌注损伤是组织器官在缺血的基础上恢复血流后，其自身损伤反而加重的现象，是外科实践中常见的组织器官损伤之一。缺血再灌注损伤在脏器严重感染、创伤、休克、脏器功能不全等疾病的病理演变过程中起了非常重要的作用。近年来，缺血再灌注损伤方面的研究比较多，尤其是关于心、脑、肺、肝等脏器的报道更为多见，但有关小肠缺血再灌注损伤的研究由于起步较晚，报道相对较少。     

小肠移植缺血再灌注损伤的防治策略

小肠对缺血敏感,术后缺血再灌注损伤(I/R)严重,影响临床小肠移植的效果。缺血预处理(IPC)、改善小肠移植保存液、抗炎等多种方法对减轻I/R显示出广阔前景,但均处于实验阶段,结合我们的研究,本文概括介绍了抗小肠I/R的方法及策略。     

肝脏缺血再灌注损伤的研究进展

肝部分切除是广泛运用于治疗肝脏良恶性肿瘤、肝内胆管结石、肝外伤等疾病,肝移植是治疗终末期肝病的唯一有效方式,但缺血再灌注损伤是肝切除术及肝移植的主要制约因素之一,其病理生理过程复杂,如何有效减轻术中缺血再灌注损伤将有助于降低手术对肝脏功能的影响.本文就缺血再灌注损伤分期、发生机制、对肝脏的不良影响及预防措施的相关研究作一综述.     

肺缺血再灌注损伤机制研究进展

在临床上肺移植、失血性休克、肺栓塞、体外循环、肺袖状切除手术等均会导致肺缺血再灌注损伤(IRI),IRI已成为肺移植术后重要的死因之一.进一步研究发生机制是解决肺IRI的重要环节.本文就肺IRI在分子生物学层面的作用机制:①炎症反应;②氧自由基;③蛋白酶;④脂类介质;⑤钙超载;⑥微循环障碍;⑦能量代谢障碍;⑧肺表面活性物质缺失等作一综述.     

罗格列酮预处理能减轻小肠缺血再灌注损伤

背景:肠缺血再灌注(I/R)是外科急腹症,不仅导致肠道局部组织坏死,还会引发全身炎症反应,对其他器官组织产生严重影响。目的:探讨罗格列酮(ROS)对小肠I/R损伤的作用及其机制。方法:18只雄性C57BL/6小鼠随机分为假手术组、I/R损伤组和ROS预处理组。ROS预处理组造模前30 min静脉注射ROS 0.3 mg/kg,以血管夹夹闭肠系膜上动脉30 min、再灌注4 h诱导I/R损伤模型。处死所有小鼠,以HE染色观察小肠黏膜病理学变化,实时定量PCR法检测小肠组织肿瘤坏死因子(TNF)-α、干扰素(IFN)-γ、白细胞介素(IL)-1β、转化生长因子(TGF)-β和Smad3 mRNA表达,蛋白质印迹法检测TGF-β、Smad3蛋白表达,ELISA法检测血清TNF-α、IFN-γ、IL-1β水平。结果:与假手术组相比,I/R损伤组小肠黏膜病理评分显著升高(P0.05),TNF-α、IFN-γ和IL-1βmRNA表达水平明显上调(P0.05),TGF-β、Smad3 mRNA和蛋白表达均明显上调(P0.05),血清TNF-α、IFN-γ和IL-1β水平明显上调(P0.05)。经ROS预处理后,上述指标均明显改善(P0.05)。结论:ROS预处理可通过抑制TGF-β/Smad3信号通路减轻炎症反应,从而减轻小肠I/R损伤。     

小肠缺血预处理对大鼠心脏缺血再灌注损伤的保护作用

目的：观察小肠缺血预处理对大鼠心脏缺血再灌注损伤的作用。方法：采用大鼠肠系膜动脉缺血预处理的方法，观察对离体心脏缺血再灌注损伤的影响。结果：缺血预处理能明显减轻心脏缺血再灌注损伤的程度，表现为乳酸脱氢酶及组织蛋白酶D漏出减少，心肌水肿程度减轻，丙二醛生成减少（P均＜0．01）。结论：小肠缺血预处理对心脏缺血再灌注损伤具有一定保护作用，表明器官间存有交叉预处理现象。     

老年大鼠小肠缺血预处理对心脏缺血再灌注损伤的影响

目的探讨老年大鼠小肠缺血预处理对心脏缺血再灌注损伤的影响。方法在大鼠离体心脏灌注模型上，观察在体小肠缺血预处理对心脏缺血再灌注损伤的影响。结果小肠缺血预处理组和心脏缺血再灌注损伤组检测结果分别为蛋白５６．３±０．７和９１．５±１５．４ｍｇ／Ｌ，乳酸脱氢酶（ＬＤＨ）１０１．２±２９．３和２３０．６±３５．９Ｕ／Ｌ，组织蛋白酶Ｄ（ＣＤ）１．４±０．４和１．９±０．５Ｕ／ｍｇ蛋白，丙二醛（ＭＤＡ）１．２±０．２和１．６±０．４μｍｏｌ／ｇｄｗ，各指标两组比较，差异有显著性（均为Ｐ＜０．０１）。蛋白激酶Ｃ（ＰＫＣ）抑制剂组上述指标明显高于预处理组。结论老年大鼠小肠缺血预处理对心脏缺血再灌注损伤具有保护作用，这种器官间的交叉预处理保护作用涉及ＰＫＣ途径。     

体外循环缺血再灌注损伤药物保护研究进展

大多心脏外科手术都需要体外循环。体外循环对脑、肾、肺及肝脏等重要脏器的损伤不可避免。体外循环期间,心脏历经低温缺血,外周组织器官低灌注,导致缺血再灌注损伤,引发系统性炎症反应,炎症介质和细胞因子大量释放,激活不同的生化途径,最终导致微血栓形成,凝血因子消耗以及出血倾向。本文将介绍体外循环后组织器官缺血再灌注损伤的机制及可能的药理学保护作用靶点,为新药研发与临床诊疗提供依据。     

Klotho在缺血再灌注损伤中的研究进展

缺血再灌注损伤在临床中十分常见且难以避免,是影响缺血性疾病治疗效果的一个重要因素。Klotho作为一种抗衰老蛋白,具有抗氧化应激、抗凋亡、抗炎、抑制钙超载等作用。本文结合国内外Klotho与缺血再灌注损伤相关疾病的最新研究报道,就Klotho与缺血再灌注损伤关系及其作用机制作一综述,为抗缺血再灌注损伤新药的后续研发提供依据。     

体外循环肺缺血-再灌注损伤的研究进展

随着体外循环机、氧合器的不断改进 ,心肌保护技术的完善和手术技巧的提高 ,心内直视手术的并发症和死亡率明显下降。但是体外循环 ,心内直视手术后急性肺功能障碍发生率仍高 ,婴幼儿、复杂型先心病、大血管疾病、高危心脏瓣膜疾病更为突出 ,急性肺损伤(ＡＬＩ)已成为术后死亡的主要原因之一。本文就缺血 再灌注过程中 ,肺泡上皮细胞和肺血管内皮细胞损伤机理作一综述。1　肺泡上皮细胞及肺泡通道损伤肺泡上皮由Ⅰ型细胞和Ⅱ型细胞组成 ,主要为Ⅱ型细胞 ,但Ⅰ型细胞覆盖绝大部分肺泡 ,Ⅰ型细胞和Ⅱ型细胞呈紧密连接 ,这种结构有利于保持肺泡…     

Pretreatment of cromolyn sodium prior to reperfusion attenuates early reperfusion injury after the small intestine ischemia in rats

AIM: To investigate the effects of Cromolyn Sodium (CS) pretreated prior to reperfusion on the activity of intestinal mucosal mast cells (IMMC) and mucous membrane of the small intestine in ischemia-reperfusion (IR) injury of rats. METHODS: Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups: sham group (group S), model group (group M), high and low dosage of CS groups, (treated with CS 50 mg/kg or 25 mg/kg, group C1 and C2). Intestinal IR damage was induced by clamping the superior mesenteric artery for 45 min followed by reperfusion for 60 min. CS was intravenouly administrated 15 min before reperfusion. Ultrastructure and counts of IMMC, intestinal structure, the expression of tryptase, levels of malondisldehyde (MDA), TNF-α, histamine and superoxide dismutase (SOD) activity of the small intestine were detected at the end of experiment. RESULTS: The degranulation of IMMC was seen in group M and was attenuated by CS treatment. Chiu’s score of group M was higher than the other groups. CS could attenuate the up-regulation of the Chiu’s score, the levels of MDA, TNF-α, and expression of tryptase and the down-regulation of SOD activity and histamine concentration. The Chiu’s score and MDA content were negatively correlated, while SOD activity was positively correlated to the histamine concentration respectively in the IR groups. CONCLUSION: Pretreated of CS prior to reperfusion protects the small intestine mucous from ischemia- reperfusion damage, the mechanism is inhibited IMMC from degranulation.     

Melatonin protects liver from intestine ischemia reperfusion injury in rats

AIM： To investigate the protective effect of melatonin on liver after intestinal ischemia-reperfusion injury in rats. METHODS： One hundred and fifty male Wistar rats, weighing 190-210 g, aged 7 wk, were randomly divided into melatonin exposure group, alcohol solvent control group and normal saline control group. Rats in the melatonin exposure group received intraperitoneal （IP） melatonin （20 mg/kg） 30 min before intestinal ischemia-reperfusion （IR）, rats in the alcohol solvent control group received the same concentration and volume of alcohol, and rats in the normal saline control group received the same volume of normal saline. Serum samples were collected from each group 0.5, 1, 6, 12, and 24 h after intestinal IR. Levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured with an auto-biochemical analyzer. Serum TNF-α was tested by enzyme-linked immunosorbent assay （ELISA）. Malondialdehyde （MDA） in liver was detected by colorimetric assay. Pathological changes in liver and immunohistochemical straining of ICAM-1 were observed under an optical microscope. RESULTS： The levels of ALT measured at various time points after intestinal IR in the melatonin exposure group were significantly lower than those in the other two control groups （P 〈 0.05）. The serum AST levels 12 and 24 h after intestinal IR and the ICAM-1 levels （%） 6, 12 and 24 h after intestinal IR in the melatonin exposure group were also significantly lower than those in the other two control groups （P 〈 0.05）. CONCLUSION： Exotic melatonin can inhibit the activity of ALT, AST and TNF-α, decrease the accumulation of MDA, and depress the expression of ICAM-1 in liver after intestinal IR injury, thus improving the liver function.     

脑缺血-再灌注损伤中炎性反应的研究进展

炎性反应在脑缺血-再灌注继发性损伤中起关键性的作用。脑缺血-再灌注激活的炎性细胞产生大量的炎性介质,如白细胞介素（interleukin,IL）、中性粒细胞趋化因子（eytokine-induced neutrophil che-moattractant,CINC）、肿瘤坏死因子α（tumor necrosis factor-alpha,TNF-α）、细     

肺移植缺血再灌注损伤肺保护的研究进展

随着医学的发展,肺移植存活率得到了明显改善。但由于肺耐受缺血时间较其它实体器官短,因而缺血再灌注损伤已经成为肺移植术后高死亡率的主要原因之一。阐明其发生机制并寻求相应的治疗措施是当今医学界亟待攻克的一项重要课题。本文就从缺血再灌注损伤的发生机制方面对肺移植缺血再灌注肺损伤保护的研究进展作一综述。     

Nitroxide radical attenuates ischaemia/reperfusion injury to the rat small intestine

Background—Free radicals are associated withpost-ischaemic intestinal injury and contribute to major clinicalproblems primarily in premature infants. Various antioxidative meansand modes of intervention, previously tested, have demonstrated onlylimited efficacy.
Aims—To study the protective activity of thestable nitroxide radical 4-OH, 2,2,6,6-tetramethylpiperidine-1-oxyl(TPL) and its respective hydroxylamine (TPL-H) againstischaemia/reperfusion (I/R) injury.
Methods—An isolated loop of ileum was created inlaboratory male Sabra rats and constantly perfused with warmed normalsaline. Intestinal injury was elicited through clamping of the superior mesenteric rat artery followed by reperfusion. Either TPL or TPL-H wasgiven intravenously immediately before ischaemia or reperfusion andcontinuously afterwards. The rate of mucosal to lumen clearance ofpara-aminohippurate (PAH) was used to evaluate intestinal mucosal injury. Serum and perfusate levels of both TPL and TPL-H were measuredusing electron paramagnetic resonance spectrometry.
Results—The increase in intestinal permeabilityinduced by I/R was significantly inhibited by both TPL and TPL-H. Thenitroxide was effective also when given immediately before reperfusion.
Conclusion—Through a continuous exchange, TPL andTPL-H act as self-replenishing antioxidants and thus protect fromintestinal injury. This demonstrates the potential of the family ofnitroxide antioxidants against oxidative stress in general and I/Rinjury in particular.

Keywords:intestinal mucosa; oxidative damage; free radicals; spin labels; antioxidants

     

Protective effect of sulfhydryl-containing antioxidants against ischemia/reperfusion injury of prepubertal rat intestine

Background and Aim:  Reactive oxygen species generated during reperfusion of the tissue are known to play an important role in the basic pathophysiology of ischemia/reperfusion (I/R) injury. The aim of this study was to investigate and compare the protective effects of three sulfide-based antioxidants, N -acetylcysteine (NAC), erdosteine (ERD), and α-lipoic acid (LA), on I/R injury of the small intestine tissue.
Methods:  Forty male Sprague–Dawley rats weighing between 100–150 g were divided into five groups ( n  = 8 for each): control (sham operated), I/R, I/R + NAC, I/R + ERD, and I/R + LA. Intestinal ischemia was provided by occluding the superior mesenteric artery via a special microvascular clamp; ischemia for 30 min and reperfusion for 3 days were carried out. Ileal specimens were obtained to determine the tissue levels of malondialdehyde (MDA), protein carbonyl contents (PCO), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities and histological changes.
Results:  The rats subjected to intestinal I/R exhibited an increase in tissue MDA and PCO; the levels could hardly be ameliorated in the treatment groups. SOD and GPx activities were significantly decreased in the I/R group, whereas their reduction was less expressed in the treatment groups. Additionally, the histopathological injury scores of the disulfide-treated groups were lower than those of the I/R group.
Conclusion:  All of the sulfhydryl-containing antioxidants used in this study exhibited a significant role in attenuating intestinal I/R injury; however, the outcome of the LA-treated group was significantly marked than that of the others.     

三碘甲状腺原氨酸和缺血预适应对大鼠小肠缺血再灌注损伤的作用

目的了解缺血预适应和Ｔ３对小肠缺血再灌注损伤的作用。方法观察缺血预适应和Ｔ３对大鼠小肠缺血再灌注后肠组织腺苷酸含量和肠粘膜损伤的影响。结果Ｔ３组和预适应组（预适应为１０分钟缺血后１５分钟再灌注）的小肠组织ＡＴＰ及总腺苷酸含量均明显高于对照组（Ｐ＜０．０５）,肠粘膜损伤亦明显减轻;且Ｔ３组比预适应组肠粘膜损伤更轻（Ｐ＜０．０５）,动物存活率增加（Ｐ＜０．０５）。结论Ｔ３和缺血预适应对小肠缺血再灌注损伤有一定保护作用,且Ｔ３效果更佳。     

Mucosal injury induced by ischemia and reperfusion in the piglet intestine: influences of age and feeding

The pathogenesis of neonatal necrotizing enterocolitis is unknown, but enteral alimentation, infectious agents, and mesenteric ischemia have been frequently invoked as primary initiators of the disease. To define the vulnerability of the intestinal mucosa to ischemia and reperfusion in the developing piglet, we evaluated changes in mucosal permeability using plasma-to-lumen clearance of chromium 51-labeled ethylenediaminetetraacetic acid in the ileum of anesthetized 1-day-, 3-day-, 2-wk-, and 1-mo-old piglets as a function of (a) duration of intestinal ischemia (20, 40, or 60 min of total superior mesenteric artery occlusion), (b) feeding status (fasted or nursed), and (c) composition of luminal perfusate (balanced salt solution vs. predigested cow milk-based formula). Baseline chromium 51-labeled ethylenediaminetetraacetic acid clearance was not significantly altered by ischemia, irrespective of duration, or feeding in all age groups. However, clearances were significantly elevated during reperfusion after 1 h of total intestinal ischemia in all age groups, whether fasted or fed. Reperfusion-induced increases in clearance did not differ among age groups when the bowel lumen was perfused with a balanced salt solution. However, luminal perfusion with formula resulted in higher clearances in 1-day-old piglets compared with all older animals. Thus, the neonatal intestine appears to be more vulnerable to mucosal injury induced by ischemia and reperfusion in the presence of formula than the intestine of older animals.     

甘露醇对大鼠小肠移植缺血再灌注损伤的保护作用

目的:探讨甘露醇对大鼠小肠移植缺血再灌注(ischemia and reperfusion,I/R)损伤的保护作用及其作用机制.方法:建立大鼠小肠移植I/R损伤模型.雄性SD大鼠随机分为假手术组、I/R组和甘露醇处理组.对I/R损伤后不同时间(0.5,1,1.5 h)的小肠标本进行组织病理学观察并检测小肠组织中超氧化物歧化酶(SOD,U/mgprot)和丙二醛(MDA,nmol/mgprot)的含量.结果:不同时间点I/R组小肠绒毛高度和黏膜厚度低于假手术组(P<0.01)和甘露醇处理组(P<0.05).不同时间点I/R组(16.24±4.56,18.50±2.89.19.42±2.21)MDA水平高于假手术组(10.26±1.72,P<0.01)和甘露醇处理组(11.24±1.51,14.03±3.12,16.06±3.62;P<0.05);而SOD水平低于假手术组和甘露醇处理组(398.36±18.81,363.16±16.29,325.66±14.58 vs 447.97±16.94;422.30±17.41,385.09±19.11,346.15±14.10;P<0.01或P<0.05).结论:甘露醇可通过清除氧自由基的方式对移植小肠缺血再灌注损伤起到保护作用.     

胃缺血再灌注损伤的模型与机制

近年来,随着临床医学的一些重要进展,缺血再灌注损伤的普遍意义已引起人们的高度重视。失血性休克、败血症、胃肠道某些血管性疾病、一些重要器官(如心、脑、肾)的损伤等常可引起急性胃粘模损伤,其损伤机制与胃的缺血再灌注密切相关,现仅就近几年来国内外对胃缺血再灌注损伤(GIRI)的研究进展作一综述。 1 动物模型的制备 1.1 夹闭支配胃的有关动脉在实验室中最常用的动物是大鼠,通常是夹闭腹腔动脉30min,松开后恢复血流1h即可见到明显的胃粘膜损伤,以后,随着再灌注时间的延长,损伤逐渐加重,再灌48h～72h损伤达高峰,此时,胃粘膜肌层破坏,形成溃