Role of ischemic preconditioning in hepatic ischemia-reperfusion injury

Background

Investigation into less traumatic method of vascular occlusion during liver resection is the actual problem in hepatic surgery because of high level of complications such as liver failure. In this connection, the goal of our study was to determine the optimal model of vascular clamping. The research showed that vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique.

Methods

Forty white giant rabbits were divided randomly into four groups (n=10 in each group). In group I we used continuous Pringle maneuver by 30 min. In group II we used intermittent Pringle maneuver: 15 min of clamping/5 min of unclamping (reperfusion)/15 min of clamping. In group III we used intermittent Pringle maneuver with ischemic precondition: 5 min of ischemia/5 min of reperfusion, 10 min of ischemia/5 min of reperfusion/15 min of ischemia. Group IV (control group) is without hepatic ischemia. All animals were performed a liver biopsy at the end of the surgery. Five rabbits from each group underwent re-laparotomy on day 3 after surgery with biopsy samples being taken for studying reparative processes in liver parenchyma.

Results

Results of morphometric analysis were the best to illustrate different level of liver injury in the groups. Thus, there were 95.5% damaged hepatocytes after vascular occlusion in hepatic preparations in group I, 70.3% damaged hepatocytes in group II, and 42.3% damaged hepatocytes in group III. There were 5.3% damaged hepatocytes in the control group.

Conclusions

Vascular occlusion with ischemic preconditioning in the mode 5/10/15 the most delicate technique that does not involve major structural injuries and functional disorders in the remnant liver. Thus, it is amenable to translation into clinical practice and may improve outcomes in liver resection with inflow vascular occlusion.     

不同肝血流阻断方法在肝癌肝切除术中应用的比较研究

目的探讨肝癌肝切除时肝血流阻断法的合理选用。方法采用半肝血流阻断、缺血预处理、间歇性全肝血流阻断3种方法行肝切除术。对3组术前、术后肝功能变化及术中出血进行比较。结果83例患者无手术死亡。术后两周肝功能恢复正常或接近术前水平,3组分别为95.8%(23/24)、74.1%(20/27)和56.3%(18/32),组间比较差异有统计学意义(P<0.05或P<0.01);术中出血量分别为(188±31.70)ml、(196±45.54)ml和(389±74.10)ml,前两组与后一组差异有统计学意义(P<0.01)。结论肝癌肝切除时选择性半肝血流阻断是减少术中出血和术后肝功能恢复较快的有效肝血流阻断方法之一。     

远端缺血预处理对老年患者胃肠道恶性肿瘤根治术后早期心肌损伤的影响

目的 探讨远端缺血预处理（RIPC）对老年患者胃肠道恶性肿瘤根治术后早期心肌损伤的影响。
方法 选择行胃肠道恶性肿瘤根治术的老年患者59例,男43例,女16例,年龄65～85岁,BMI 18～35 kg/m²,ASA Ⅱ或Ⅲ级。将患者随机分为两组：远端缺血预处理组（RIPC组,n=27）和对照组（C组,n=32）。RIPC组于麻醉后、手术开始前进行3个循环的RIPC,每个循环行单侧下肢缺血5 min,再灌注5 min;C组不做处理。两组麻醉方案和手术操作均相同。记录术后24、48 h的肌钙蛋白I（cTnI）、C反应蛋白（CRP）、白细胞介素-6（IL-6）、丙二醛（MDA）、超氧化物歧化酶（SOD）、内皮型一氧化氮合成酶（eNOS）、诱导型一氧化氮合成酶（iNOS）浓度,以及术后48 h D-二聚体、纤维蛋白降解产物（FDP）浓度。记录心肌损伤（cTnI≥0.2 μg/L）以及术后30 d内的主要心血管不良事件的发生情况。
结果 与C组比较,RIPC组术后24、48 h cTnI明显降低,术后24 h CRP、IL-6明显降低,术后24、48 h MDA明显降低,术后48 h eNOS、iNOS明显升高,D-二聚体、FDP浓度明显降低（P＜0.05）。两组心肌损伤、术后30 d主要心血管不良事件的发生率差异无统计学意义。
结论 远端缺血预处理能降低胃肠道恶性肿瘤根治术后早期心肌损伤标志物cTnI的释放,减轻术后炎症反应、氧化应激、高凝状态并改善血管内皮功能,但不能降低心肌损伤以及术后30 d内主要心血管不良事件的发生率。     

肝脏缺血预处理在肝癌围手术期中的作用

目的 观察缺血预处理(ischemic preconditioning,IP)在肝癌围手术期的作用.方法 IP组35例,对照组25例,IP组肝切除前采用10min/10 min的缺血预处理,肝门阻断方法(Pringle手法)、肝切除方法与步骤与对照组类似,比较两组术前、术后肝酶的变化、术中出血与输血量、术后并发症、住院天数、住院费用的区别.结果 两组术中肝门阻断时间、出血量、输血量无明显区别(P>0.05).术后两组肝酶均有明显升高,但IP组谷丙转氨酶在术后1 d、3 d、7 d的升高值明显低于对照组(P<0.025),IP组术后肝功能不全的发生率、住院天数和住院费用明显较对照组低(P<0.05).结论 肝癌手术时采用缺血预处理为一简单有效的保护肝功能的方法.     

缺血预处理对肢体缺血再灌注损伤的影响

目的　观察缺血预处理 (IPC)对肢体缺血再灌注损伤的影响。方法　选择 2 0例需充气止血带止血进行手术的患者 ,随机分为对照组 (n =10 )和IPC组 (n =10 )。IPC组患者术前应用 3次 5min循环缺血 ,间隔 5min再灌注预处理后在止血带下进行手术 ;对照组直接在止血带下进行手术。在肢体缺血前和再灌注 30min、90min、180min分别取静脉血检测血清肌酸磷酸激酶 (CPK)、谷草转氨酶(AST)、乳酸脱氢酶 (LDH)、丙二醛 (MDA)和过氧化物歧化酶 (SOD)水平。结果　随着肢体缺血再灌注时间的延长 ,血中CPK、AST、LDH、MDA含量逐渐升高 ,而SOD活性逐渐降低。IPC组在缺血前及再灌注同时间 ,血中CPK、AST、LDH、MDA含量低于对照组 (P <0 0 5 ,P <0 0 1) ;而SOD活性高于对照组 (P <0 0 5 ,P <0 0 1)。结论　IPC能有效地减轻肢体缺血再灌注损伤程度 ,减轻脂质过氧化反应 ,提高肢体缺血耐受性     

Ischemic preconditioning of skeletal muscle mitigates remote injury and mortality

BACKGROUND: Ischemic preconditioning (IPC) mitigates ischemia-reperfusion (I/R) injury in experimental models. However, the clinical significance of this protection has been unclear and a mortality reduction has not been previously reported in noncardiac models. This study examined the local and remote protection afforded by skeletal muscle IPC and sought to determine the significance of this protection on mortality. METHODS: Mice subjected to 2 h hindlimb ischemia/24 h reperfusion (standard I/R injury) were compared with those undergoing a regimen of two 20-min cycles of IPC followed by standard I/R injury. Local injury was assessed via gastrocnemius histology, and remote injury was evaluated via intestinal histology and pulmonary neutrophil infiltration (n = 7). Mortality was compared in parallel groups for 1 week (n = 6). Groups were analyzed using an unpaired Student's t-test for gastrocnemius and pulmonary injury, and a Mann-Whitney rank sum test for intestinal injury. Mortality differences were interpreted through a hazard ratio. RESULTS: Significant protection was observed in preconditioned animals. There was a 35% local injury reduction in skeletal muscle (71.2% versus 46.0%, P < 0.01), a 50% reduction in remote intestinal injury (2.3 versus 1.1, P < 0.01), and a 43% reduction in remote pulmonary injury (14.9 versus 8.5, P < 0.01) compared with standard injury controls. Preconditioned animals were also significantly protected from mortality, demonstrating a 66.7% survival at 1 wk compared with 0% survival after standard injury alone (hazard ratio 0.20, 95% CI: 0.02-0.59). CONCLUSIONS: We have developed a murine model of IPC that demonstrates local and remote protection against I/R injury, and exhibits significant mortality reduction. This model demonstrates the powerful effect of IPC on local and remote tissues and will facilitate further study of potential mechanisms and therapies.     

缺血预处理加用川芎嗪抑制肠缺血再灌注性肝细胞凋亡

目的研究缺血预处理加川芎嗪抑制肠缺血再灌注大鼠肝细胞凋亡并探讨其可能机制。方法健康SD大鼠50只,随机分为假手术对照(sham,S)组、肠缺血再灌注(intestine ischemical reperfusion,IIR)组、川芎嗪治疗(ligustrazine,LGT)组、缺血预处理(ischemic preconditioning,IPC)组和川芎嗪 缺血预处理(LGT IPC)组5组。用免疫组化法检测肝组织Bcl-2和Bax蛋白表达,用末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记(terminal deoxynucle-otidyltransferase mediated dUTP nick end labeling,TUNEL)技术检测肝细胞凋亡,并测定肝组织超氧化物歧化酶(superoxide dismutase,SOD)和丙二醛(malondialdehyde,MDA)含量。结果LGT IPC组肝细胞凋亡指数明显低于除S组外的其他各组,Bcl-2蛋白表达明显增多,Bax蛋白表达明显减少,Bcl-2/Bax比值增高。同时LGT IPC组肝组织SOD活性增高,MDA含量降低。结论缺血预处理与川芎嗪联合应用对抑制肠缺血再灌注所致的肝细胞凋亡具有显著的协同作用。     

肝脏尾状叶巨大肿瘤切除手术经验

施行肝脏尾状叶巨大肿瘤手术４例．其中２例为肝脏多发性海绵状血管瘤．２例为原发性肝癌．术式：左或右半肝切除并肝尾叶切除２例；肝尾叶切除并肝左叶血管瘤剥除１例；巨大左肝尾状叶肿瘤切除、并左肝外叶切除、右肝小癌灶无水乙醇注射１例。１例出院后因癌复发转移．术后２．５个月死亡；３例治愈出院．经６～１７个月随访健在．肝尾状叶巨大瘤块切除是难度大、风险大的手术．本文介绍了具体操作的几点体会．并对难以切除的肝肿瘤行一期或二期手术问题提出自己的看法．     

Protective effect of ischemic preconditioning against intermittent warm-ischemia-induced liver injury

BACKGROUND: Although ischemic preconditioning (IPC) has been reported to protect the liver from injury when subjected to continuous hepatic ischemia, whether IPC protects rat livers against ischemia-reperfusion (I/R) injury after intermittent ischemia has not been elucidated. MATERIALS AND METHODS: Five groups of Wistar rats were subjected to intermittent hepatic ischemia (I) comprising 15-min ischemia and 5-min reperfusion three times with or without prior IPC (10-min ischemia and 10-min reperfusion), 45-min continuous ischemia (C) with or without IPC, and sham operation. Serum transaminase and lactic acid levels, hepatic tissue energy charges, and hepatic blood perfusion were measured after reperfusion. Plasma tumor necrosis factor-alpha (TNF-alpha) levels were determined after reperfusion for 120 min. Histological and apoptotic findings were evaluated after reperfusion for 180 min. RESULTS: IPC significantly reduced serum transaminase levels after continuous and intermittent ischemia (IPC + C, 1107 vs C, 2684 IU/l; IPC + I, 708 vs I, 1859 IU/l). After hepatic ischemia without IPC, apoptosis and necrosis with increased plasma TNF-alpha levels were observed. IPC protected livers from injury by interfering with the increase in plasma TNF-alpha (IPC + I, 27.6 vs I, 64.8 pg/ml; IPC + C, 21.6 vs C, 49.3 pg/ml). This resulted in the attenuation of hepatic necrosis after continuous ischemia and significantly reduced necrosis and apoptosis after intermittent ischemia. CONCLUSIONS: IPC exerts a greater protective effect against hepatic I/R injury after intermittent hepatic ischemia than after continuous hepatic ischemia.     

Treatment for accidental occlusion of the hepatic artery after hepatic resection: Report of two cases

(Received for publication on Oct. 22, 1997; accepted on May 15)     

缺血预处理对大鼠肝脏缺血/再灌注早期核因子κB活性及细胞凋亡的影响

目的 观察缺血预处理对大鼠肝脏缺血/再灌注早期核因子KB活性、促凋亡基因Fas和FasL蛋白表达以及肝细胞凋亡的影响,以进一步阐明肝脏缺血预处理的抗凋亡作用机制.方法 建立SD大鼠肝缺血(40min)再灌注(120 min)损伤及肝缺血预处理的模型.24只大鼠随机分成3组(n=8).①假手术对照组(C组),仅分离肝十二指肠韧带,不阻断肝门,不进行其他干预处理.②缺血再灌注组(IR组),在第一肝门用小血管夹阻断尾状叶及左肝叶血流40 min松开血管夹肝脏再灌注2 h,再灌注开始后关腹.③缺血预处理组(IP组),先行3个循环的缺血预处理,阻断第一肝门10 min,开放再灌注10 min为1个循环,随后操作同缺血/再灌注组.实验结束后全自动生化分析仪检测血清谷草转氨酶和血清谷丙转氨酶活性:TUNEL法检测肝组织的细胞凋亡指数(AI):EMSA法测定肝组织核因子κB的结合活性:Western blotting免疫印迹法检测Fas及FasL蛋白的表达水平.结果 IR组和IP组的ALT、AST及细胞凋亡指数(AI)均明显高于S组(P<0.01),但与IR相比,IP组则明显较低(P<0.01).与C组比较,IR组的核因子κB活性、促凋亡基因Fas和FasL蛋白表达水平明显增高,而IP组仅轻度增高.结论 缺血预处理可通过降低肝脏缺血/再灌注早期核因子κB的转录活性,并下调促凋亡基因Fas及FasL的表达,从而发挥抗细胞凋亡和损伤保护效应.     

TNF-alpha is required for late ischemic preconditioning but not for remote preconditioning of trauma

BACKGROUND: Ischemic preconditioning (IPC) and remote IPC are cardioprotective phenomena in which ischemia of the myocardium or of a remote tissue, respectively, induces cardioprotection. Despite clinical evidence that surgical trauma can remotely affect myocardial infarction, to date there are no basic science studies addressing the effect of nonischemic trauma at distant sites upon cardiac ischemia/reperfusion (I/R) injury. The objectives of this study were to determine the effects of nonischemic remote surgical trauma upon infarct size after myocardial I/R and to determine the effects of TNF-alpha ablation upon cardioprotective phenomena. MATERIALS AND METHODS: A minimally traumatic mouse model was used to ascertain the effect of remote nonischemic surgical trauma upon I/R injury. TNF-alpha knockout mice were employed to determine the effect of TNF-alpha ablation. RESULTS: Carotid artery vascular surgery remotely exacerbates cardiac I/R injury increasing infarct size by 287% (remote cardiac injury or RCI). Nonischemic, nonvascular trauma (abdominal incision) results in remote preconditioning of trauma (RPCT), decreasing infarct size by 81% (early phase) and 40% (late phase) relative to controls. Finally, TNF-alpha is required for late IPC but is not necessary for RCI or for RPCT. CONCLUSIONS: We show that late IPC is TNF-alpha-dependent and describe two unique TNF-alpha-independent remote effects of nonischemic trauma upon myocardial infarction. Understanding the mechanism of these remote effects will allow the development of novel therapies for the treatment of ischemic heart disease. RPCT and TNF-alpha ablation have an additive protective effect suggesting that combinations of complementary approaches may be a useful strategy for maximizing the clinical efficacy of cardioprotective therapies.     

缺血预处理对大鼠肝移植受体的保护性作用

目的:观察缺血预处理对肝移植后早期C-X-C类趋化因子的表达和中性粒细胞浸润的影响,以探讨其保护作用的机制.方法:建立大鼠肝移植模型,供肝于UW液保存24 h.实验分大鼠肝移植组(未处理组)和缺血预处理组,后者于供肝切取前夹闭第一肝门10 min然后开放10 min取肝.于移植后1 h、2 h、4 h、6 h分别测定肝内髓过氧化物酶(myeloperoxidase,MPO)活性和血清肝酶学指标、巨噬细胞炎性蛋白(macrophage inflammatory protein,MIP)-2、肿瘤坏死因子(tumor necrosis factor,TNF)-α水平.分别取术后4 h肝组织行常规病理切片.结果:肝酶学指标改变显示缺血预处理组肝功能得到有效改善.缺血预处理组较未处理组肝MPO水平在各时点均有降低,并在移植后4 h(0.48±0.18 U/g组织和0.85±0.11 U/g组织)和6 h(0.63±0.04 U/g组织和0.77±0.05 U/g组织)出现显著性差异(P<0.05).血清MIP-2水平亦在4 h和6 h显著下降(2546.59±707.78 pg/ml和3488.82±785.15 pg/ml,1023.72±656.86 pg/ml和1852.04±1108.89 pg/ml).血清TNF-α水平仅在2 h变化显著(370.77±146.82 pg/ml和517.41±57.30 pg/ml).结论:本研究认为缺血预处理可能通过下调肝细胞对趋化因子的表达,减少移植肝内中性粒细胞的浸润,从而对供肝起保护作用.     

Intermittent Ischemic Preconditioning Protects Against Hepatic Ischemia-Reperfusion Injury and Extensive Hepatectomy in Steatotic Rat Liver

ABSTRACT

Background: Hepatic steatosis causes severe liver damage and has deleterious effects when associated with ischemia-reperfusion mechanisms. Ischemic preconditioning (IPC) protects lean liver against prolonged ischemia by improving micro-circulation and reducing lipid peroxidation. We investigated the effect of intermittent IPC on liver ischemia-reperfusion injury (IRI) and extensive hepatectomy in severe hepatic steatosis. Methods: Severe hepatic steatosis was performed by 12–14 weeks of choline-free diet in 108 Wistar rats. We induced 30-minute ischemia-reperfusion manipulations and extensive hepatectomy with or without prior IPC in steatotic livers and after 6 and 24 hours of reperfusion blood transaminases, and IL6, TNFα, NO and Lactate in blood and liver tissue were measured. Results: Steatotic rats subjected to hepatic ischemia-reperfusion alone after extensive hepatectomy, showed severe liver damage with significantly increased values of AST, ALT, TNFα and Lactate and significantly reduced IL6 and NO, while no one rat survived for more than 29 hours. On the contrary, steatotic rats subjected to intermittent IPC, 24 hours before ischemia-reperfusion, presented increased 30-day survival (67%), lower values of AST, ALT, TNFα and Lactate, and increased IL6 and NO levels. Simple and intermittent IPC manipulations, 1 hour before the IRI and extended hepatectomy, did not prolong survival more than 57 and 98 hours, respectively. Simple IPC, 24 hours before IRI and extended hepatectomy had the lowest possible survival (16.7%).Conclusions: Hepatic steatosis and IRI after major liver surgery largely affect morbidity and mortality. Intermittent IPC, 24 hours before IRI and extensive hepatectomy, presents higher 30-day survival and improved liver function parameters.     

远隔缺血预处理对肺损伤患者预后的临床研究Meta分析

目的 系统性评价远隔缺血预处理(remote ischemic preconditioning,RIPC)对各种原因导致的肺损伤的影响.方法 通过检索PubMed、Embase、Medline、中国知网(CNKI)、维普中文期刊全文数据库、中国生物医学文献数据库、中国生物医学期刊引文数据库,根据纳入标准和排除标准,检索出相关随机对照临床研究文献,并提取主要评估指标(ICU停留时间及机械通气时间)和次要评估指标[术后24 h血清IL-6、TNF-α、IL-8浓度及肺泡动脉氧分压差(alveolar-arterial oxygen tension gradient,A-aDO2)、氧合指数(oxgension index,PaO2/FiO2)、呼吸指数(respiratory index,RI)],采用RevMan5.3和STATA 12.0软件进行Meta分析. 结果 共纳入前瞻性随机对照研究8篇,476例患者,其中RIPC组237例,对照组239例.与对照组相比,RIPC可以减少患者术后ICU停留时间及机械通气时间,并降低术后24 h血清TNF-α浓度(P＜0.05),其标准均数差(standard mean difference,SMD)和95％CI分别为-0.03(-0.41,-0.05)、-0.2(-0.39,-0.01)、-0.85(-1.35,0.34). 结论 RIPC可以减少患者术后ICU停留时间和机械通气时间,改善肺损伤患者的临床预后.     

Effects of liraglutide and ischemic postconditioning on myocardial salvage after I/R injury in pigs*

Objectives. Acute STEMI is routinely treated by acute PCI. This treatment may itself damage the tissue (reperfusion injury). Conditioning with GLP-1 analogs has been shown to reduce reperfusion injury. Likewise, ischemic postconditioning provides cardioprotection following STEMI. We tested if combined conditioning with the GLP-1 analog liraglutide and ischemic postconditioning offered additive cardioprotective effect after reperfusion of 45?min coronary occlusion of left anterior descending artery (LAD). Design. Fifty-eight non-diabetic female Danish Landrace pigs (60?±?10kg) were randomly assigned to four groups. Myocardial infarction (MI) was induced by occluding the LAD for 45?min. Group 1 (n?=?14) was treated with i.v. liraglutide after 15?min of ischemia. Group 2 (n?=?17) received liraglutide treatment concomitant with ischemic postconditioning, after 45?min of ischemia. Group 3 (n?=?15) recieved ischemic postconditioning and group 4 (n?=?12) was kept as controls. Results. No intergroup differences in relative infarct size were detected (overall mean 57?±?3%; p?=?0.68). Overall mortality was 34% (CI 25–41%) including 26% post-intervention, with no intergroup differences (p?=?0.99). Occurrence of ventricular fibrillation (VF) was 59% (CI 25–80%) including 39% postintervention with no intergroup differences (p?=?0.65). Conclusions. In our closed-chest pig-model, we were unable to detect any cardioprotective effect of liraglutide or ischemic postconditioning either alone or combined.     

阿霉素预处理替代缺血预处理提供鼠肝缺血耐受力的实验研究

目的 探讨缺血预处理（IPC）延迟保护作用的发生机制以及应用阿霉素预处理（DPC）是否可以模拟IPC的延迟保护作用。方法 建立大鼠部分肝脏热缺血再灌注模型。IPC组采用肝脏缺血10min，再灌注10in，DPC组经静脉注射阿霉素（1mg/kg体重），对照组等量生理盐水注射。肝组织HSP70和HO－1蛋白和血清TNF－α、IL－10浓度分别采用Western blot法和ELISA法测定。结果 IPC后HO－1和HSP70含量分别于12h和24h达到高峰；IPC和DPC后24h诱导HSP70、HO－1的量无显著差异（P＞0.05）。对照组缺血再灌注后3h血清中TNF－α、AST、ALT、LDH及W／D（湿重／干重）的水平明显升高，而IL－10的含量降低，和假手术组相比差异显著（P＜0.01）；IPC或DPC后降低了TNF－α的释放和AST、ALT、LDH及W／D的水平，提高了IL－10的含量，和对照组相比差异显著（P＜0.01）。结论 IPC的延迟保护作用与HSP70和HO－1的诱导生成有关，DPC可以模拟IPC的延尺性保护作用，诱导HSP70和HO－1的产生。     

缺血预处理对鼠后肢缺血再灌注下脊髓腰骶膨大运动神经元的保护作用

[目的]对大鼠一侧后肢的缺血再灌注损伤行不同条件缺血预处理,观察脊髓腰骶膨大处运动神经元超微结构的变化,探讨其保护作用.[方法]通过血管夹暂时阻断大鼠左侧髂总、髂内和髂外动脉,建立大鼠后肢缺血模型.以缺血6h再灌注2h和12 h分为A、B两组,预处理方式为缺血10 min血液复流10 min,按无预处理、预处理1次、无时间间隔预处理2、3次,分成A0、A1、A2、A3;B0、B1、B2、B3组.取材腰骶膨大处脊髓灰质前角,光镜及透射电镜下观察不同条件预处理对缺血再灌注损伤中脊髓前角超微结构变化.[结果]组织形态观察结果显示A0组缺血再灌注损伤后神经元细胞减少,核溶解消失,损伤明显,预处理后神经元细胞增多,可见部分细胞核存在;B0组缺血再灌注损伤后神经元细胞大部分坏死溶解,预处理后坏死溶解现象减轻.超微结构观察显示A0和B0组脊髓前角神经兀细胞不同程度核周器扩张损伤,出现内质网扩张、大量线粒体空泡以及核膜溶解消失.预处理后损伤程度有所减轻,叠加预处理后损伤进一步减轻.[结论]缺血预处理能减轻大鼠肢体缺血再灌注下脊髓腰骶膨大运动神经元的损伤,对脊髓具有保护作用.反复3次预处理产生的保护作用优于2次预处理及1次预处理.     

不同时间的缺血预处理对肝硬化大鼠缺血再灌注损伤的保护作用

目的 探讨缺血预处理(IPC)对肝硬化大鼠缺血再灌注损伤(I/R)的保护作用,并寻找对肝硬化I/R保护作用的最佳有效时间窗和理想方案.方法 通过构建正常大鼠及肝硬化大鼠模型,以正常肝脏I/R(A组)和正常肝脏10-10 min-IPC方案(B组)为对照组,肝硬化组则分别施行单纯I/R(C组)、5-10 min(D组)、8-10min(E组)、10-10 min(F组)及15-10 min(G组)的IPC方案,每组18只,分别在术后1 h、4 h及24 h三个时间点采静脉血,检测血清ALT、AST、LDH及肝组织中MDA、MPO、NO、SOD水平,评价肝功能及肝脏组织炎性浸润及抗损伤程度.结果 肝脏缺血30 min后肝脏功能受损明显,表现为各组的ALT、AST、LDH水平升高,尤以再灌注4 h时显著(P<0.05),但经过缺血预处理后,各IPC组中的NO、MDA、MPO及SOD水平亦显著高于其对应的I/R组,以E组的差别有显著意义(P<0.05).结论 10-10 min的IPC方案对于正常肝脏I/R确有保护作用,而8-10 min的IPC方案能最有效地启动对肝硬化大鼠肝脏I/R的保护作用.     

Efficacy of repeat hepatic resection for recurrent hepatocellular carcinomas

Background: This study evaluated the efficacy of repeat hepatic resection for recurrent hepatocellular carcinoma (HCC) and the clinicopathological factors influencing overall survival after resection. Methods: From 1992 to 2005, 231 patients underwent curative hepatic resection for HCC at Yokohama City University, Japan. Of these, 105 patients developed intrahepatic recurrence, and 24 repeat hepatectomies were performed for recurrent HCC. Survival data were analysed, and prognostic factors for repeat hepatic resection were determined. Results: The overall cumulative 1‐, 3‐ and 5‐year survival rates and the median survival time of the patients after initial hepatic resection (n= 231) did not differ from those of the patients after repeat hepatic resection (n= 24), with values of 91.3, 70.2 and 49.1%, and 57 months, versus 91.7, 73.1 and 50.9%, and 61.5 months, respectively (P= 0.875). The operative time and blood loss in patients who underwent repeat hepatic resection did not differ from those who underwent primary resection. Multivariate analysis identified portal invasion at the first hepatic resection and a disease‐free interval of ≤1.5 years after primary hepatic resection as independent risk factors for survival after repeat hepatic resection. The 12 patients who did not show either of the two prognostic factors had 3‐ and 5‐year survival rates of 91.7 and 68.8%, respectively, after repeat hepatic resection. Conclusions: Our findings suggest repeat hepatic resection as the treatment of choice for recurrent HCC patients without portal invasion at the first resection whose recurrence develops after a disease‐free interval of >1.5 years since the previous surgery.