缺血预处理对移植肝缺血再灌注损伤中细胞凋亡的影响

目的 探讨细胞凋亡在移植肝缺血再灌注损伤中的作用及缺血预处理对其影响。方法 通过对移植肝进行 因预处理,用全自动生化分析仪检测肝功能、比色法测定移植肝组织的ＭＤＡ、用流式细胞仪结合原位标记技术检测细胞调７亡。结果 移植肝再灌注后血中ＡＳＴ、ＡＬＴ、ＬＤＨ和肝组织中ＭＤＡ均明显升亮,肝细胞调亡明显增加,经缺血预处理后,血中ＡＳＴ,ＡＬＴ,ＬＤＨ和肝组织中ＭＤＡ均降低,肝细胞调亡亦明显减少,结论 缺血     

不同缺血预处理方案对小鼠肝缺血再灌注损伤的影响

肝脏缺血再灌注（ischemia-reperfusion，I／R）损伤是临床常见的问题，是肝脏手术患者术后恢复慢甚至手术失败的重要原因之一。缺血预处理（ischemic preconditioning，IPC）可减轻肝脏I／R损伤。我们通过比较不同IPC方案对C57BL／6小鼠肝脏I／R损伤的影响，为寻找合理有效的IPC方案提供依据。     

缺血缺氧预处理与肺缺血／再灌注损伤

人及多种哺乳类动物实验证实，短时夹闭1开放肺根或单独夹闭，开放主支气管造成的肺短暂缺血后再灌注及短时缺氧后再复氧，可启动肺预处理保护效应，对肺缺血／再灌注损伤有明显防治作用，本文对该领域的研究现状作一综述。     

肝移植缺血再灌注损伤与细胞粘附分子

自本世纪80年代以来,伴随着手术技巧的提高、新型免疫抑制剂和UW保存液的相继问世,临床肝移植取得了长足的进步。然而,缺血再灌注损伤依然是困扰着肝移植的研究难点,它是引发术后原发性移植物无功能(primary graftnonfunction)的重要原因。而随着近年来对细胞粘附分子研究的不断深入,表明细胞粘附分子恰恰参与并介导了缺血再灌注损伤过程中的各个步骤。本文综述近年来在此领域的研究进展。 一、细胞粘附分子的种类、结构与功能 细胞粘附分子分布极其广泛,涉及生命活动的许多现象,包括细胞分裂、分化以及细胞凋亡的调控等等。根据结构与功能,粘附分子可初步分为5类,即整合素家族、免疫球蛋白超家族、选择素家族、钙粘附蛋白家族和其它粘附分子。前三者是参与肝移植过程中缺血再灌注等炎症反应和免疫应答的重要家族。     

逆灌注对移植肝缺血再灌注损伤的影响

目的:探讨原位肝移植中经下腔静脉逆行灌注对移植肝缺血再灌注损伤的影响.方法:36例大鼠肝移植随机分为3组,每组12例.门静脉组即经门静脉顺行灌注,肝动脉+门静脉组即同时开放肝动脉及门静脉顺行灌注,下腔静脉组即先吻合下腔静脉后开放逆行灌注,然后吻合门静脉及肝动脉.分别检测术后1、6及24 h的血清转氨酶、移植肝病理变化及...     

不同时间的缺血预处理对脂肪肝缺血再灌注损伤的保护作用

目的探讨缺血预处理（IP）对脂肪肝缺血再灌注（IR）损伤的保护作用,以及取得最佳效果的预处理时间。方法通过建立大鼠脂肪肝模型,给予不同时间的IP（5-10、8-10、10-10、15-10 min）和IR（缺血30 min,再灌注30 min）,检测血清AST、ALT、LDH及NO水平,肝组织中MDA、SOD、MPO含量的变化和肝脏病理学变化。以脂肪肝未行IP组和正常肝脏未行IP组及正常肝脏行10-10 min IP作对照。结果 IR后,脂肪肝未行IP组血清肝功能的变化、肝组织病理学改变及炎性浸润程度显著重于正常肝脏未行IP组。在脂肪肝组中,5或8-10 min IP组血清学及肝组织MDA、MPO水平低于其余组和未行IP组,而其SOD水平显著升高（P〈0.05）。各IP组中的NO水平明显高于其对应的IR组（P〈0.05）。脂肪肝IP组中,5或8-10 min IP组血清NO水平明显高于其余组（P〈0.05）。结论脂肪变性加重肝脏IR损伤,IP对脂肪肝的IR损伤具有保护作用,本实验认为5～8 min缺血和10 min再灌注的IP方案可能是中重度脂肪肝时的最佳预处理方案。     

丙泊酚预处理与缺血预处理保护大鼠体外心脏缺血再灌注损伤作用的比较

目的:以缺血预处理(IPC)为标准观察丙泊酚预处理对大鼠体外心脏再灌注损伤的保护作用并探索其可能机制。方法:建立大鼠体外心脏Langendorff灌流模型并随机分为对照组(A组, n=8)、丙泊酚预处理组(B组,n=6)、IPC组(C组,n=6)及5 羟癸酸(5 HD)对照组(D组,n=8)、5 HD加丙泊酚预处理组(E组,n=6)、5 HD加 IPC组(F组,n=7)共6组。连续记录各组心脏血流动力学指标及冠状动脉流量变化,进行再灌注性心律失常评分,并计算心脏梗死面积。结果:B、C、E组血流动力学指标、冠状动脉流量、心律失常评分、梗死面积显著优于A组,以C组最显著(P<0.01或0.05),而D、F组与A组比较差异无统计学意义。结论:丙泊酚预处理与 IPC均可改善体外大鼠心脏再灌注所致的血流动力学紊乱、冠状动脉循环受损及再灌注性心律失常的发生,并缩小心脏梗死面积,但丙泊酚上述保护效应较 IPC弱。阻滞线粒体 KATP通道开放对丙泊酚预处理作用无影响,推测该通道与其保护效应无关。     

Preconditioning and postconditioning reduce hepatic ischemia-reperfusion injury in rats

BACKGROUND:Ischemia-reperfusion injury occurs when ischemic tissues or organs suffer from further functional and structural damage when their blood supply recovers.This study aimed to contrast the protective effects of ischemic preconditioning and ischemic postconditioning in hepatic ischemia-reperfusion injury in rats.METHODS:Thirty-two healthy male Wistar rats were randomly divided into four groups:sham-operated(SO),ischemia-reperfusion(IR),ischemic preconditioning(I-pre),and ischemic postconditioning(I-p...     

Doxorubicin preconditioning: a protection against rat hepatic ischemia-reperfusion injury

Doxorubicin produces clinically useful responses in a variety of human cancers. However, the toxicity of doxorubicin has limited its usefulness. This side effect is mainly due to the doxorubicin-mediated free radical formation. Administration of doxorubicin (10 mg/kg body weight) to rats intravenously induces heme oxygenase-1 (HO-1) in the liver. The levels of HO-1 protein were first detected at 6 hours and peaked at about 18 to 24 hours after the injection. It is known that HO-1 plays a protective role against the oxidative injury. Therefore, we have examined the protective effect of doxorubicin preconditioning against the hepatic ischemia-reperfusion injury. Partial hepatic ischemia was produced in the left and medium lobes for 45 minutes followed by 120 minutes reperfusion. When low doses of doxorubicin (1 mg/kg body weight) was intravenously administered to rats 2 days before the ischemia, the serum alanine transaminase (ALT) levels in the preconditioning rat were clearly improved compared with those in the rat without preconditioning. Under this situation, zinc-protoporphyrin IX, a specific inhibitor of HO-1, was injected subcutaneously to rats at 3 and 16 hours before the ischemia, the ALT levels were not improved by doxorubicin preconditioning. Histopathologic examination also supported these results. Although the HO-1 protein level was fairly low 2 days after the doxorubicin administration, significant amounts of HO-1 protein were detected. Our results indicated that the induction of HO-1 played a protective role against hepatic ischemia-reperfusion injury and that doxorubicin preconditioning is more clinically useful than other preconditioning methods.     

肝脏缺血再灌注损伤机制及干预的研究进展

肝脏缺血再灌注损伤(HIRI)是一个多因素共同作用的过程,在一定程度上制约了肝脏外科的发展。深入研究HIRI的机制,制订合理的干预治疗策略,对提高患者预后起着积极的作用。介绍了HIRI的相关发生机制,主要涉及钙超载、Kupffer细胞、微循环障碍、活性氧的产生、补体、非编码RNA以及各种细胞因子等多种因素,各个因素共同作用,导致肝细胞的坏死、凋亡。此外,自噬作为第二类细胞死亡方式,也参与了HIRI。鉴于HIRI的机制复杂,涉及因素众多,需从多方面着手干预。指出随着缺血预处理、亚低温以及氢气等干预方法的出现,新型的治疗方法有望为临床干预HIRI治疗带来新的思路。     

靶向自噬缓解肝缺血再灌注损伤的研究进展

肝缺血再灌注损伤(HIRI)是肝切除和肝移植术后常见的临床问题,是导致移植术后肝功能障碍和肝功能衰竭的主要原因。近年来,自噬介导的途径成为缓解HIRI的研究热点。自噬是指细胞通过将大量细胞质、受损细胞器等底物运输到溶酶体内进行消化降解以不断更新重塑再利用细胞的过程。本文从基因、蛋白、信号通路、炎症反应、氧化应激反应、线粒体及内质网应激等方面总结了靶向自噬途径缓解HIRI相关机制的研究进展,并围绕研究中存在的问题进行了讨论和展望,以期为今后通过靶向自噬途径缓解HIRI的研究提供理论支持。     

Low-dose TNF-alpha protects against hepatic ischemia-reperfusion injury in mice: implications for preconditioning

Tumor necrosis factor alpha (TNF-alpha) is implicated in the pathogenesis of hepatic ischemia reperfusion injury but can also prime hepatocytes to enter the cell cycle. Ischemic preconditioning protects against ischemia-reperfusion (IR) liver injury and is associated with activation of nuclear factor kappaB (NF-kappaB) and cell cycle entry. We examined the pattern of TNF-alpha release during hepatic IR in the presence or absence of ischemic preconditioning, and we tested whether a single low-dose injection of TNF could mimic the biologic effects of ischemic preconditioning. In na?ve mice, hepatic and plasma levels of TNF-alpha rose during hepatic ischemia, reaching high levels after 90 minutes; values remained elevated during reperfusion until 44 hours. Following the ischemic preconditioning stimulus, there was an early rise in hepatic and serum TNF-alpha levels, but, during a second prolonged ischemic interval peak, TNF-alpha values were lower than in na?ve mice and declined to negligible levels by 2 hours reperfusion. An injection with 1 microg or 5 microg/kg body weight TNF-alpha 30 minutes prior to hepatic IR substantially reduced liver injury determined by liver histology and serum alanine aminotransferase (ALT) levels. As in ischemic preconditioning, TNF-alpha pretreatment activated NF-kappaB DNA binding, STAT3, cyclin D1, cyclin-dependent kinase 4 (cdk4) expression, and cell cycle entry, determined by proliferating cell nuclear antigen (PCNA) staining of hepatocyte nuclei. In conclusion, the hepatoprotective effects of "preconditioning" can be simulated by TNF-alpha injection, which has identical downstream effects on cell cycle entry. We propose that transient increases in TNF-alpha levels may substitute for, as well as, mediate the hepatoprotective effects of ischemic preconditioning against hepatic IR injury.     

大豆异黄酮对大鼠肝脏缺血再灌注损伤的保护作用

肝脏缺血再灌注损伤(HIRI)的机制尚未阐明,可能与活性氧(ROS)生成、细胞因子参与、肝细胞内钙离子超载、细胞凋亡等有关[1].大豆异黄酮(SI)是人们公认的抗氧化剂及抗炎药物.研究结果表明,其对心肌、脑等器官缺血再灌注损伤具有保护作用[2-3].但对HIRI是否具有保护效应,鲜见报道.本研究通过动物实验观察了SI对HIRI的保护作用.     

Local regulators of hepatic sinusoidal microcirculation: recent advances

This article reviews our recent studies on the local regulation of hepatic microcirculation with special reference to the inlet sphincter-like structures, the roles of sinusoidal endothelial cells and the mechanism of dynamic changes in the sinusoidal endothelial fenestrae (SEF) as well as in the terminal portal venules and the terminal hepatic arterioles induced by the potent vasoconstrictor endothelin (ET)-1. There are two types of sphincter-like structures at the entering sites of hepatic sinusoids. One is located at the junction between the terminal portal venule and the sinusoid, and is characterized by the large endothelial cells surrounded with Ito cells (hepatic stellate cells: HSCs). The other is located at the junction between the terminal hepatic arteriole and the sinusoid, and corresponds to the precapillary sphincter since our enzymohistochemical demonstration of arterial capillaries in close association with the sinusoids combined with intravital microscopy has revealed that the terminal hepatic arteriole directly terminates in the sinusoid. It is essential for the local control of hepatic sinusoidal blood flow that the dynamic contracting and relaxing changes not only in these inlet sphincter-like structures but also in the SEF correspond with those of the HSCs, both of which are mediated by the sinusoidal endothelium-derived vasoconstrictor endothelins (ETs) and vasodilator nitric oxide (NO). The contractility of the SEF and HSCs depends on the intracellular Ca++-calmodulin-actomyosin system.