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肠缺血-再灌注损伤(ischemia- reperfusion injury,简称I/R)是外科实践中的重要问题,在小肠移植、严重感染、创伤、休克、心肺功能不全等疾患的病理演变过程中起重要作用。肠I/R的后果,不仅可以引起肠粘膜的局部组织损害,而且可以导致肠道菌群移位和肠吸收功能的改变,以及远处器官的损害,甚至发生多系统器官功能不全综合症。本文阐述了近年来在其发生机理及防治措施方面的研究进展,为今后临床工作提供指导。 相似文献
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为了研究重组人B型钠尿肽(recombinant human B-type natriuretic peptide, rhBNP)对减轻大鼠心肌缺血再灌注损伤的机制,本研究采用尾部静脉注射的方法对I/R大鼠成功建模,并设计注射生理盐水(I/R组)、rhBNP (I/R+rhBNP组)和假手术组CK组3个处理组,通过TUNEL法检测各处理组大鼠心肌细胞的凋亡情况。本实验还用生理和生化方法检测了心肌细胞中超氧化物歧化酶(superoxidedismutase, SOD)和丙二醛(malondialdehyde, MDA)活性和含量的变化情况,用RT-PCR和免疫印迹方法检测了Bax/Bcl-2信号通路中基因和蛋白表达水平变化。结果表明,rhBNP可以提高I/R大鼠心肌细胞中SOD酶活性,同时使MDA含量降低,表明rhBNP能够保护心肌细胞,使细胞受损程度减小。与此同时本研究发现rhBNP处理后大鼠心肌细胞中Bax基因和蛋白的表达量显著下调,且Bcl-2基因和蛋白的表达显著上调,从而使I/R大鼠心肌细胞的凋亡数目减少,缩小心肌坏死的面积。本研究表明rhBNP可以通过调节Bax/Bcl-2信号通路、提高SOD酶活性使I/R大鼠心肌细胞内MDA含量减少,以及心肌细胞凋亡数目减少,从而有效地减轻大鼠心肌缺血再灌注损伤,以达到保护心肌细胞的目的。 相似文献
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肠缺血—再灌注时肺损伤机制的探讨及硫酸锌的保护作用 总被引:1,自引:0,他引:1
已知缺血再灌注(I/R)所致多器官损伤与氧自由基产生增多有关,其中肺脏是最易受损的器官之一,锌是人体必须的微量元素,对机体有广泛的影响。已有文献报道,锌可对抗大鼠急性脑缺血再灌注损伤。本研究采用肠I/R损伤模型,研究肠I/R时入、出肺血及肺组织超氧化物岐化酶(SOD)、丙二醛(MDA)及肺表面活性物质(PS)含量的变化,进而了解I/R时肺损伤的改变及机制,并探讨硫酸锌对其损伤的保护作用。1 材料及方法(1)动物分组及处理 健康杂种兔26只,体重(25±0.5)kg,雌雄兼用,乌拉坦(1g/kg)静脉麻醉,分离右颈静脉和左颈动脉,全身肝… 相似文献
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目的:探讨七叶皂苷钠对肠缺血/再灌注肠过氧化损伤的影响及其机制。方法:复制大鼠肠缺血/再灌注(I/R)损伤模型,观察七叶皂苷钠对血浆和肠组织超氧化物歧化酶(SOD)、丙二醛(MDA)、二胺氧化酶(DAO)、髓过氧化物酶(MPO)的影响,同时观察肠组织水肿和病理损害。结果:七叶皂苷钠可显著改善肠损伤,降低肠组织湿/干比值及含水率,同时升高血浆和肠组织SOD活性,降低血浆和肠组织MPO活性及MDA含量(P〈0.01)。结论:七叶皂苷钠对肠I/R后肠黏膜具有保护作用,其机制可能与抑制中性粒细胞的聚集与活化,对抗脂质过氧化损伤有关。 相似文献
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目的:观察胰岛素对大鼠肠缺血再灌注后小肠组织损伤的影响。方法:雄性SD大鼠40只随机分为4组,每组10只,手术对照组、单纯缺血组、再灌注组、胰岛素干预组。于30min缺血和120min再灌注后,进行组织病理学和生化检测。结果:(1)单纯缺血组肠粘膜损害较手术对照组明显升高(P<0.01),超氧化物歧化酶(SOD)活性无明显变化;(2)再灌注组SOD活性明显降低,与手术对照组和单纯缺血组相比较差异均有显著性(P<0.01);(3)胰岛素组SOD活性与再灌注组相比有明显改善(P<0.01)。结论:肠缺血可以引起肠粘膜损伤,再灌注则可加重这种损伤,胰岛素可以减轻再灌注损伤。 相似文献
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目的:观察胰岛素对大鼠肠缺血再灌注后小肠组织损伤的影响。方法:雄性SD大鼠40只随机分为4组,每组10只,手术对照组、单纯缺血组、再灌注组、胰岛素干预组。于30min缺血和120min再灌注后,进行组织病理学和生化检测。结果:(1)单纯缺血组肠粘膜损害较手术对照组明显升高(P〈0.01),超氧化物歧化酶(SOD)活性无明显变化;(2)再灌注组SOD活性明显降低,与手术对照组和单纯缺血组相比较差异均有显著性(P〈0.01);(3)胰岛素组SOD活性与再灌注组相比有明显改善(P〈0.01)。结论:肠缺血可以引起肠粘膜损伤,再灌注则可加重这种损伤,胰岛素可以减轻再灌注损伤。 相似文献
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补阳还五汤对脑缺血/再灌注大鼠脑组织MDA和SOD作用的研究 总被引:8,自引:0,他引:8
近年来研究发现,机体代谢过程中产生的自由基及其脂质过氧化作用在脑缺血/再灌注损伤的病理生理过程中发挥着重要作用,但在多数研究中动物模型的缺血时间或再灌注时间较短,与临床病例的实际情况及脑组织凋亡出现的高峰期(2~4d)有一定差距.补阳还五汤是治疗缺血性脑血管疾病及其后遗症的有效方剂,为探讨其作用机理本文研究了该方对脑缺血45 min再灌注3d的大鼠血清及脑组织丙二醛(MDA)含量和脑组织超氧化物歧化酶(SOD)活力的影响. 相似文献
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目的:观察红花注射液对兔肠缺血/再灌注损伤超微结构的影响,探讨其机制。方法:复制在体兔肠缺血/再灌注损伤模型。30只日本大耳兔,随机均分为3组(n=10):假手术组(S组),缺A/再灌注组(I/R组)和缺血/再灌注+红花注射液组(SI组)。使用电镜观察各组肠组织标本超微结构的改变,作对比分析。结果:L/R组多数肠粘膜上皮细胞肿胀,胞质内液泡增多,大多数线粒体呈不同程度的肿胀,严重者可见嵴减少或消失,内质网扩张较明显,细胞表面微绒毛数量明显减少且排列较乱,部分微绒毛有肿胀、融合现象,上皮细胞间隙扩大,连接较疏松。粘膜下间质可见少量的浆细胞浸润现象,部分毛细血管周围可见水肿现象。SI组在上述部位的病理改变均明显减轻。结论:红花能有效减少炎性渗出,抑制微循环通透性的增加,阻断肠缺血/再灌注损伤进展的病理生理过程,对肠组织超微结构有良好保护作用。 相似文献
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肠缺血/再灌注损伤后白介素1-β水平与磷脂酶A2激活的关系 总被引:7,自引:0,他引:7
为了探讨肠缺血/再灌注损伤后IL-1β基因表达和蛋白含量变化与磷脂酶A2抑制之间的关系,采用大鼠肠缺血/再灌注损伤模型,在对照组,损伤组和磷脂酶A2抑制剂处理组动物中收集血清,肺灌洗液,腹腔灌洗液及全身重要脏器组织样品,采用放射免疫法测定IL-1β含量,并且RT-PCR法测定肺组织中IL-1β和Ⅱ型PLA2基因表达,结果表明,损伤后6h血清中IL-1β含量明显高于对照组;损伤后1和3h,腹腔注保IL-1β也明显高于对照组;损伤后肝组织中IL-1β水平有明显增加,而肺,肾、肠组织中IL-1β没有明显变化。损伤后肺灌洗液中IL-1β也明显高于对照组水平,肺组织中IL-1βmRNA表达增加,而Ⅱ型PLA2mRNA在损伤后表达反而有所下降,采用磷脂酶A2抑制剂氯喹,环氧化物酶抑制剂消炎痛,血小板活化因子受体阻断剂SR27417后,IL-1β蛋白和基因表达有不同的改变,提示肠缺血/再灌注损伤后一定时间内,肝内IL-1βmRNA表达和血中IL-1β水平明显增高,但是否与磷脂酶A2激活或其代谢产物的释放有关尚需进一步证明。 相似文献
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Neurotoxic Esterase in Human Nervous Tissue 总被引:1,自引:1,他引:0
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Li Diao David Patsouris Ali-Reza Sadri Xiaojing Dai Saeid Amini-Nik Marc G Jeschke 《Molecular medicine (Cambridge, Mass.)》2015,21(1):959-968
Extensively burned patients often suffer from sepsis, a complication that enhances postburn hypermetabolism and contributes to increased incidence of multiple organ failure, morbidity and mortality. Despite the clinical importance of burn sepsis, the molecular and cellular mechanisms of such infection-related metabolic derangements and organ dysfunction are still largely unknown. We recently found that upon endoplasmic reticulum (ER) stress, the white adipose tissue (WAT) interacts with the liver via inflammatory and metabolic signals leading to profound hepatic alterations, including hepatocyte apoptosis and hepatic fatty infiltration. We therefore hypothesized that burn plus infection causes an increase in lipolysis of WAT after major burn, partially through induction of ER stress, contributing to hyperlipidemia and profound hepatic lipid infiltration. We used a two-hit rat model of 60% total body surface area scald burn, followed by intraperitoneal (IP) injection of Pseudomonas Aeruginosa-derived lipopolysaccharide (LPS) 3 d postburn. One day later, animals were euthanized and liver and epididymal WAT (EWAT) samples were collected for gene expression, protein analysis and histological study of inflammasome activation, ER stress, apoptosis and lipid metabolism. Our results showed that burn plus LPS profoundly increased lipolysis in WAT associated with significantly increased hepatic lipid infiltration. Burn plus LPS augmented ER stress by upregulating CHOP and activating ATF6, inducing NLRP3 inflammasome activation and leading to increased apoptosis and lipolysis in WAT with a distinct enzymatic mechanism related to inhibition of AMPK signaling. In conclusion, burn sepsis causes profound alterations in WAT and liver that are associated with changes in organ function and structure. 相似文献
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Necroptosis不同于坏死和凋亡,具有坏死的细胞形态特点和自噬的活化,并且是主动耗能的,是被一系列信号传导通路所调控的细胞死亡机制。Necroptosis的发现和确认为细胞死亡的逆转和治疗开创了一个新的研究和应用途经。RIPl激酶是调控Necroptosis形成的关键酶,Necrostatins则是一类小分子化合物,它通过特异性地抑制细胞RIPl激酶而抑制Necroptosis的形成。 相似文献
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Non-apoptotic Functions of Caspase-3 in Nervous Tissue 总被引:5,自引:0,他引:5
Gulyaeva NV 《Biochemistry. Biokhimii?a》2003,68(11):1171-1180
Some enzymes that have been recognized as "apoptotic" so far may be involved in important cellular processes not necessarily related to cell death in nervous tissue. The activity of caspase-3, an "apoptotic" enzyme, can be measured in normally functioning neurons. The results reported by several groups point to the possibility that caspases may be involved in nervous tissue function as top enzymes in the regulatory proteolytic cascade. A concept on a new mechanism of synaptic plasticity modulation involving caspase-3 has been formulated postulating a specific role of caspase-3 in normal brain functioning. The idea of synaptic plasticity modulation by caspase-3 is in line with data reported recently. For example, caspase-3 is possibly involved in the long-term potentiation (LTP) phenomenon since proteins that are key players of molecular mechanisms of LTP induction and maintenance are caspase-3 substrates. Experimental results on blocking LTP by a caspase-3 inhibitor confirm this concept. 相似文献
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Staining of Nervous Tissue by Protein-Silver Mixtures 总被引:1,自引:0,他引:1
A. Peters 《Biotechnic & histochemistry》1958,33(1):47-53
A staining method for nerves in paraffin sections is described in which an egg albumen-silver nitrate mixture is the impregnating solution. Blocks of tissue are fixed in Bouin's fixative, formol, Huber's fixative or formol-acetic-alcohol, and decalcified if necessary in Bensley's decalcifier. Sections are impregnated overnight, in the dark, at 37-56°C in a solution containing 50 ml of filtered, aqueous 0.5% dried egg albumen with 1.8-2.5 ml of 2% silver nitrate and adjusted to pH 8.2-8.3 by the addition of ammonia. The sections are then rinsed in distilled water and the silver reduced in a mixture of hydroquinone, 1 gm; anhydrous sodium sulfite, 10 gm and distilled water, 100 ml. The remainder of the process consists of washing, gold toning, fixing in 5% sodium thiosulfate, washing, dehydrating, clearing and mounting. Casein may be used as an alternative to egg albumen in the impregnating solution (0.5% casein, 50 ml; 2% silver nitrate, 1 ml). The pH value of the solution may be adjusted by a boric acid-borax buffer or ammonium hydrogen tetraborate in the place of ammonia. 相似文献
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Eduardo De Robertis Hersch M. Gerschenfeld Flora Wald 《The Journal of cell biology》1958,4(5):651-658
A study of myelination with electron microscopy has been carried out on the spinal cord of young rats and cats. In longitudinal and transverse sections the intimate relationship of the growing axons with the oligodendrocytes was observed. Early naked axons appear to be embedded within the cytoplasm and processes of the oligodendrocytes from which they are limited only by the intimately apposed membranes of both elements (axon-oligocytic membrane). In a transverse section several axons are observed to be in a single oligodendrocyte. The process of myelination consists in the laying down, within the cytoplasm of the oligodendrocyte and around the axon, of concentric membranous myelin layers. The first of these layers is deposited at a certain distance (200 to 600 A or more) from the axon-oligocytic membrane. This and all the other subsequently formed membranes have higher electron density and are apparently formed by the coalescence and fusion of vesicles (of 200 to 800 A) and membranes found in large amounts within the cytoplasm of the oligodendrocytes. At an early stage the myelin layers may be discontinuous and some vesicular material may even be trapped among them or between the myelin proper and the axon-oligocytic membrane. Then, when the 8th to 10th layer is deposited, the complete coalescence and alignment of the lamellae leads to the characteristic orderly multilayered organization of the myelin sheath. Myelination in the central nervous system appears to be a process of membrane synthesis within the cytoplasm of the oligodendrocyte and not a result of the wrapping of the plasma membranes as postulated in Geren's hypothesis for the peripheral nerve fibers. The possible participation of Schwann cell cytoplasm in peripheral myelination is now being investigated. 相似文献