线粒体途径在肝脏缺血再灌注损伤中的作用的研究进展

肝胆外科手术常发生肝脏缺血再灌注损伤,并且术后肝功能恢复及预后与之密切相关。虽然肝脏缺血再灌注损伤的机制复杂多样,但线粒体结构功能障碍是重要的参与者。本综述旨在总结肝脏缺血再灌注过程中线粒体变化、线粒体自噬和凋亡在缺血再灌注损伤中的作用。为减轻肝脏缺血再灌注损伤提供新靶点和新思路。     

线粒体自噬在缺血再灌注损伤中的研究进展

缺血再灌注损伤是指缺血组织或器官再次获得血流灌注时对组织、器官造成的损伤作用.而缺血再灌注损伤时,线粒体即可产生的大量的活性氧且线粒体通透性发生改变从而诱发线粒体白噬.线粒体白噬功能的紊乱与机体多种疾病的发生有着密切的关系.本文旨在介绍近年来线粒体白噬的研究进展,重点阐述其在缺血再灌注损伤中的作用及机制.     

海马神经细胞线粒体通透性转换孔在富氢液减轻大鼠全脑缺血再灌注损伤中的作用

目的 评价海马神经细胞线粒体通透性转换孔(mPTP)在富氢液减轻大鼠全脑缺血再灌注损伤中的作用.方法 雄性SD大鼠72只,体重250 ～ 300 g,采用随机数字表法,将其随机分为6组(n=12):假手术组(S组)、缺血再灌注组(IR组)、生理盐水组(NS组)、富氢液组(H组)、苍术苷组(A组)和富氢液+苍术苷组(HA组).采用四血管阻塞法建立大鼠全脑缺血再灌注模型,缺血15 min后恢复灌注.H组和HA组于再灌注即刻腹腔注射富氢液5 ml/kg,其余组腹腔注射等容量生理盐水;A组和HA组于再灌注前10 min行侧脑室注射苍术苷15 μl,NS组和H组侧脑室注射等容量生理盐水.再灌注24h时行神经行为学损伤评分后各组随机处死8只大鼠,迅速断头,分离海马神经细胞线粒体,采用分光光度计法测定mPTP的开放程度,Rhodamine123法测定线粒体膜电位.再灌注72 h时各组处死4只大鼠,取海马组织,光镜下观察CA1区病理学结果,计数该区神经细胞存活数.结果 与S组比较,其余组再灌注24h时行为学损伤加重,mPTP活性升高,线粒体膜电位降低(P＜0.05);与IR组比较,H组和HA组再灌注24h时行为学损伤减轻,mPTP活性降低,线粒体膜电位升高(P＜0.05);与H组比较,HA组行为学损伤加重,mPTP活性升高,线粒体膜电位降低(P＜0.05).再灌注72 h时HA组较IR组神经细胞存活数增加(P＜0.05),H组海马CA1区神经元损伤较IR组、NS组、A组和HA组减轻.结论 富氢液可减轻大鼠全脑缺血再灌注损伤,其机制与抑制海马神经细胞mPTP开放,减少线粒体膜电位降低,从而维持线粒体功能有关.     

线粒体通透件转换孔在缺血/再灌注损伤中的作用

背景 线粒体作为“能量工厂”提供细胞生长及代谢所需的三磷酸腺苷（adenosine triphosphate,ATP）,同时也是细胞存活与否的重要信号管理者.线粒体通透性转换孔（mitochondrial permeability transition pore,mPTP）是横跨线粒体内外膜之间的允许相对分子质量1.5 kD以下的分子自由通过的孔道.在脑缺血/再灌注（ischemia/reperfusion,I/R）损伤中,线粒体是研究的焦点,而mPTP作为线粒体的门户更是影响着线粒体膜电位（mitochondrial membrane potential,△ψm）、线粒体Ca2＋超载及促细胞死亡物质释放等一系列过程. 目的 对mPTP在I/R损伤中可能的作用机制及治疗方法进行综述. 内容 整理和阐述了mPTP的结构、mPTP与I/R损伤的机制和预防与治疗I/R损伤的可能方法. 趋向 随着mPTP在I/R损伤中的作用机制不断被揭示,其将成为治疗I/R损伤的重要靶点.     

促红细胞生成素与肾缺血再灌注损伤

缺血再灌注损伤(IRI)在肾移植过程中是不可避免的，近来研究发现促红细胞生成素(EPO)能显著减轻肾脏的IRI，保护肾脏的结构和功能。本文综述了EPO在肾脏缺血再灌注损伤中的作用及可能机制。     

缺血再灌注对脑组织钙和线粒体钙含量的影响

用“四动脉闭塞法”制成兔全脑缺血再灌注损伤模型，测其脑组织钙和线粒体钙含量变化。结果揭示：脑组织钙和线粒体钙在长时间缺血后虽有增加，但升高主要发生在再灌注期，这与我们用焦锑酸钾组化技术观察到的细胞内钙沉集情况和超微结构改变规律一致，证实钙在缺血再灌注脑损伤中具有重要作用。文中探讨了钙的内流途径和细胞损伤机制，对脑复苏治疗具有重要意义。     

肾缺血再灌注损伤与线粒体功能障碍的研究进展

肾缺血再灌注损伤(RIRI)是一个多途径的病理和生理过程,涉及复杂的发生发展机制,其中包含了肾脏线粒体稳态平衡引起的功能紊乱,与肾脏线粒体氧化应激、自噬、凋亡、动力学和再生等密切相关。这些事件相互作用,从多条途径参与了RIRI过程,是其发生发展的重要原因。本文就线粒体与RIRI相关机制的最新研究进展进行综述,为基于线粒...     

p53在肾脏缺血再灌注损伤发生机制中的作用

肾脏缺血再灌注损伤是急性肾功能衰竭的主要原因，细胞凋亡在肾缺血再灌注损伤的发生机制中有着重要地位。本文综述了近年来有关p53在肾缺血再灌注损伤后细胞凋亡和细胞周期调控方面的研究进展。     

脂肪变性供肝缺血再灌注损伤的机制研究进展

缺血再灌注损伤会影响肝移植术后肝功能恢复, 脂肪供肝则会加重上述情况。本文从细胞和分子角度分析了脂肪肝缺血再灌注损伤的发生机制, 包括线粒体功能障碍, 内质网应激和自噬的启动, 泛素-蛋白酶体系统的失衡及各种效应分子等, 为减少并预防肝脏移植术后缺血再灌注损伤的发生提供新的研究思路。     

心肌缺血再灌注损伤的线粒体通透性转换机制

线粒体功能障碍存心肌缺血再灌注（ischema／reperfusion I／R）损伤中占有重要地位．近年研究发现线粒体的功能障碍和线粒体通透性转换孔道（mitochondfial permeability transition pore，mPTP）密切相关，     

Regulation and Pathological Role of Bid in Ischemic Acute Kidney Injury

Bid, a BH3-only member of the Bcl-2 family proteins, is most abundantly expressed in the kidneys. Recent research has shown Bid activation in renal tubular cells in vitro following ATP-depletion and hypoxic injury, and also in vivo during renal ischemia-reperfusion in rats and mice. Importantly, Bid-deficient mice are resistant to ischemic kidney injury. Targeting Bid may therefore offer a new strategy for the treatment of acute renal failure associated with ischemia-reperfusion.     

Regulation and pathological role of bid in ischemic acute kidney injury

Bid, a BH3-only member of the Bcl-2 family proteins, is most abundantly expressed in the kidneys. Recent research has shown Bid activation in renal tubular cells in vitro following ATP-depletion and hypoxic injury, and also in vivo during renal ischemia-reperfusion in rats and mice. Importantly, Bid-deficient mice are resistant to ischemic kidney injury. Targeting Bid may therefore offer a new strategy for the treatment of acute renal failure associated with ischemia-reperfusion.     

Neutrophil gelatinase-associated lipocalin-mediated iron traffic in kidney epithelia

PURPOSE OF REVIEW: Neutrophil gelatinase-associated lipocalin (NGAL) is a member of the lipocalin superfamily of carrier proteins. NGAL is the first known mammalian protein which specifically binds organic molecules called siderophores, which are high-affinity iron chelators. Here, we review the expression, siderophore-dependent biological activities and clinical significance of NGAL in epithelial development and in kidney disease. RECENT FINDINGS: NGAL expression is rapidly induced in the nephron in response to renal epithelial injury. This has led to the establishment of NGAL assays that detect renal damage in the human. Additionally, only when complexed with siderophore and iron as a trimer, NGAL induces mesenchymal-epithelial transition (or nephron formation) in embryonic kidney in vitro and protects adult kidney from ischemia-reperfusion injury in vivo. While the structure of the NGAL: siderophore: iron complex has thus far only been solved for bacterially synthesized siderophores, new evidence suggests the presence of mammalian siderophore-like molecules. SUMMARY: NGAL is rapidly and massively induced in renal epithelial injury and NGAL: siderophore: iron complexes may comprise a physiological renoprotective mechanism. The data have implications for the diagnosis and treatment of acute renal injury.     

雷帕霉素对肾脏缺血再灌注损伤的影响

移植肾在经历缺血再灌注损伤后可以产生不同程度的损伤,而雷帕霉素作为临床上常用的免疫抑制剂,又可对再灌注的移植肾产生多方面的影响.本文就雷帕霉素对肾脏缺血再灌注损伤的影响作一综述.     

管周毛细血管损伤在肾移植中作用的研究进展

肾脏是一个高度血管化的器官,管周毛细血管网络是其微血管系统中关键组成部分。管周毛细血管作为肾小管及肾间质的主要供应血管,参与肾小管的能量代谢、物质分泌和重吸收等重要生理过程。近年来研究发现,肾移植过程中的缺血-再灌注损伤、排斥反应以及肾脏纤维化过程均会引起管周毛细血管结构完整性破坏、数量减少,并加重移植肾间质纤维化,严重影响肾功能的长期稳定。因此,本文对管周毛细血管的结构与功能,管周毛细血管与缺血-再灌注损伤、排斥反应以及移植肾纤维化进行综述,聚焦肾移植期间管周毛细血管的损伤机制和特异性改变,为防治肾移植围手术期并发症,改善移植物的长期预后提供参考。     

NLRP3炎症小体与相关炎症信号通路在肾缺血-再灌注损伤中的作用

肾缺血-再灌注损伤（IRI）常见于肾移植术中,是引起急性肾衰竭的重要病理生理过程,严重影响受者预后。炎症反应在IRI的发病机制及病理过程中占据着重要地位。活化的NOD样受体蛋白3（NLRP3）炎症小体可通过介导多种促炎因子的成熟与释放,调节机体炎症反应及相关细胞功能。本文对肾IRI中的NLRP3炎症小体及其相关炎症信号通路的作用机制进行了总结,旨在为临床肾IRI的防治提供新思路。     

Decreased renal ischemia-reperfusion injury by IL-16 inactivation

T-cell-mediated renal injury is a major cause of kidney transplant rejection and renal failure; hence, understanding T-cell migration within the kidney is important for preventing renal injury. Interleukin (IL)-16 is a T-cell chemoattractant produced by leukocytes. Here we measured IL-16 expression in the kidney and its role in renal ischemia-reperfusion injury induced by different conditions in several strains of mice. IL-16 was strongly expressed in distal and proximal straight tubules of the kidney. The IL-16 precursor protein was cleaved to a chemotactic form in cultured tubular epithelial cells. Inactivation of IL-16 by antibody therapy or IL-16 deficiency prevented ischemia-reperfusion injury as shown by reduced levels of serum creatinine or blood urea nitrogen compared to control mice. Further studies indicated that fewer CD4-cells infiltrated the post-ischemic kidneys of IL-16-deficient mice and that the protective effect of IL-16 antibody treatment was lymphocyte-dependent. Our results suggest that IL-16 is a critical factor in the development of inflammation-mediated renal injury and may be a therapeutic target for prevention of ischemia-reperfusion injury of the kidney.     

Antioxidant effect of zinc on acute renal failure induced by ischemia-reperfusion injury in rats

Zinc may have an antioxidant effect mediated by induction of metallothionein. Based on the assumption that metallothionein can scavenge oxygen free radicals, we examined whether zinc administration prior to renal ischemia would improve renal dysfunction caused by ischemia-reperfusion injury in rats. Wistar rats weighing 265 g were treated with an intraperitoneal injection of 20 mg/kg zinc 24 h prior to the renal ischemia-reperfusion procedure, which was achieved by a 30-min clamping of the bilateral renal vessels and subsequent 90-min reperfusion. Thirty-minute renal clearance tests were performed before and after renal ischemia in zinc- (n = 11) and saline-treated (n = 8) rats. Thiobarbituric acid reactive substance, conjugated diene, and metallothionein levels in the renal tissues were also determined. Sham-operated rats (n = 5 in each treatment) served as control for the ischemia-reperfusion rats. Ischemia-reperfusion resulted in significantly lower glomerular filtration rate values and marked increases in tissue concentrations of thiobarbituric acid reactive substance and conjugated diene compared with sham-operation. Zinc administration improved the reduced glomerular filtration rate values seen after the ischemia-reperfusion procedure, but not to the extent of pre-ischemic levels. Zinc pretreatment significantly reduced the increased levels of thiobarbituric acid reactive substance and conjugated diene during ischemia-reperfusion and increased metallothionein levels compared with saline injection. These findings suggest that zinc has an antioxidant effect mediated through the induction of metallothionein, but appears only to have a minor protective effect on renal function induced by renal ischemia-reperfusion injury. Copyright Copyright 1999 S. Karger AG, Basel