硫化氢对大鼠肝缺血再灌注损伤的影响

目的 评价硫化氢对大鼠肝缺血再灌注损伤的影响.方法 健康雄性SD大鼠30只,体重220～250 g,采用随机数字表法,将其随机分为假手术组(S组)、缺血再灌注组(IR组)和不同剂量硫化氢组(H2S1～3组),每组6只.S组仅暴露肝门,不夹闭动、静脉;IR组采用夹闭左、中叶肝蒂、门静脉和肝动脉支1h恢复灌注的方法制备大鼠肝缺血再灌注模型;H2S1～3组于再灌注前5min分别腹腔注射14、28、56 μmol/kg硫化氢钠.于再灌注6h时抽取下腔静脉血样并取肝组织,采用全自动生化分析仪测定血清谷丙转氨酶(ALT)和谷草转氨酶(AST)活性,采用二硫代二硝基苯甲酸法测定肝组织谷胱甘肽(GSH)含量,光镜下观察肝组织病理学结果.结果 与S组相比,IR组血清ALT和AST活性升高,肝组织GSH含量下降(P＜0.05);与IR组相比,H2S1～3组ALT和AST活性降低,肝组织GSH含量升高(P＜0.05);H2S1～3组肝病理学损伤较IR组明显减轻.结论 H2S可减轻大鼠肝缺血再灌注损伤.     

肠腔分流条件下巴马小型猪缺血再灌注肝功及病理变化

目的探讨肝缺血再灌注过程中肝功能及病理变化规律。方法将18头正常小型猪随机分为A组(入肝血流阻断90min)、B组(入肝血流阻断100min),对照观察两组动物在缺血前、复流前、复流1h及术后各时相点ALT、AST及肝组织病理的变化情况。结果(1)A组长期存活率为100%,B组长期存活率为44.4%;(2)两组动物于缺血及复流1hALT水平变化较术前无明显变化(P>0.05),至术后2、3d均显著高于术前水平(P<0.05),术后4d与术前无显著差异(P>0.05),术后2、3d时B组水平均显著高于A组(P<0.05);(3)两组动物于复流1h时AST水平达到峰值(P<0.05),此后AST水平逐渐下降,到术后3d与术前无显著性差异(P>0.05),复流1h,术后1、2d时B组水平显著高于A组(P<0.05);(4)两组动物肝组织病变随着缺血时间的延长而更加严重,在复流1h时肝组织损伤最为严重,随后肝组织损伤逐渐减轻,存活动物于术后4d肝组织结构基本恢复正常,死亡动物尸检见肝组织大片溶解坏死;(5)对比ALT、AST与肝组织病理学变化的关系可以看到,在肝IR过程中,ALT水平变化与肝组织变化趋势不一致,而AST水平变化与肝组织病理改变情况基本一致。结论(1)在长时间缺血过程中如发现肝组织出现灶性坏死、细胞广泛气球样变、脂肪变性将提示组织损伤难以恢复,动物难以耐受肝缺血再灌注损伤;(2)在肝脏缺血过程中检测血清ALT、AST并不能用于判断肝缺血再灌注损伤的预后情况,但再灌注过程中血清AST水平能较好的反映肝组织的受损程度。     

Synthetic sulfonolipids deduced from sulfonoquinovosyl diacylglycerols of sea urchin reduces hepatic ischemia-reperfusion injury in rats

BACKGROUND: In hepatic surgery and liver transplantation, ischemia-reperfusion (I/R) is an unavoidable process, and protection against hepatic I/R injury is a major unresolved problem. In this study, we investigated whether 3-O-(6-deoxy-6-sulfono-beta-D-glucopyranosyl)-1,2-di-O-acylglycerol bound to saturated C18 fatty acids (beta-SQAG9), which was derived from sea urchin intestines, could reduce this injury. This agent was recently reported to have immunosuppressive effects in allogeneic rat skin grafts. MATERIALS & METHODS: Male Lewis rats were divided into two experimental groups. Group 1 rats were injected with SQAG9 (50 mg/kg) into the penile vein 15 minutes before the induction of ischemia and into the portal vein just reperfusion. The same amounts of normal saline were injected into rats in the control group (group 2). Each experimental groups included six rats. Seventy percent hepatic ischemia (20 minutes) was induced by occluding the blood vessels and bile duct with a vascular clamp. For examination of hepatic function, serum levels of aspartate aminotransferase, (AST) alanine transaminase (ALT), and lactic dehydrogenase (LDH) were measured. In addition, histological examination was also assessed. RESULTS: Three hours after reperfusion, the mean plasma concentration of AST, ALT, LDH in group 1 was suppressed compared with group 2. Six hours after reperfusion, the hepatic damage in group 1 was mild in comparison with that in group 2. CONCLUSIONS: Our data demonstrated that SQAG-9 reduced the warm hepatic I/R injury.     

入肝血流阻断和全肝血流阻断对胆道梗阻兔肝脏损伤的研究

目的 研究入肝血流阻断和全肝血流阻断对胆道梗阻兔肝脏的缺血-再灌注损伤。方法 36只兔随机均分为3组:胆道梗阻组(A组,BCDL)、入肝血流阻断组(B组,PTC)和全肝血流阻断组(C组,THVE)。组织气体分析仪持续测定肝组织氧分压(P_(ti)O_2);全自动生化仪测定血流总胆红素(TBIL)、丙氨酸氢基转氨酶(ALT);光镜观察肝脏病理改变。结果 B、C组在肝血流阻断后,肝 P_(ti)O_2值均明显下降,再灌注 60 min仅恢复到缺血前的 87.5％和 73.4％(P<0.05),C组较 B组肝P_(ti)O_2 值恢复更慢(P<0.05)。B、C两组 ALT值在肝缺血-再灌注期间均有不同程度升高,C组ALT值升高更明显,且与肝细胞损伤的病理学改变相一致。结论 急性胆道梗阻兔行PTC和THVE均可导致肝脏缺血-再灌注损伤,PTC较THVE对肝脏的损伤明显减轻。     

2-Arachidonoylglycerol increases in ischemia-reperfusion injury of the rat liver.

Several studies have implicated endocannabinoids in various forms of shock. However, the role of endocannabinoids in hepatic ischemia-reperfusion injury remains unclear. The purpose of this study was to evaluate the changes of two endocannabinoidsin hepatic ischemia-reperfusion injury: anandamide (ANA) and 2-arachidonoylglycerol (2-AG). Male Sprague-Dawley rats were divided into 2 groups: the short (15 min) ischemic group and the long (60 min)ischemic group in the segmental (70%) hepatic tissue. Blood levels of aspartate transaminase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), ANA, and 2-AG were examined. Serum lev-els of AST, ALT, and LDH were significantly higher in the long-ischemia group than in the short-ischemia group. Plasma levels of 2-AG showed similar augmentation prior to and after reperfusion in both the short- and long-ischemia groups, although plasma 2-AG lev-els tended to be higher in the long-ischemia group than in the short-ischemia group. Plasma levels of ANA were augmented in the early phase of reperfusion in the short-ischemia group and did not differ significantly from the normal level with time after reperfusion in the long-ischemia group. These results suggest that the endocannabinoid 2-AG increases in hepatic ischemia-reperfusion injury of rats, rather than ANA.     

Pirfenidone protects endotoxin-induced liver injury after hepatic ischemia in rats

BACKGROUND: Pirfenidone (PFD), an experimental antifibrotic agent, was investigated for its effects on endotoxin-induced liver injury after hepatic ischemia-reperfusion. METHODS: Male Sprague-Dawley rats were subjected to 30 minutes of partial hepatic ischemia, followed by reperfusion for 24 hours. Lipopolysaccharide (LPS) was injected at 30 minutes of reperfusion. PFD (300 mg/kg) or its vehicle (0.5% carboxymethylcellulose) was given orally following LPS administration. RESULTS: PFD prevented the increase in activities of serum alanine transaminase, aspartate transaminase, and lactate dehydrogenase after reperfusion. PFD inhibited the increase of cytokine-induced neutrophil chemoattractant in serum and liver tissue. The number of neutrophils infiltrating the liver was significantly lower in the PFD-treated group than the control group. CONCLUSION: These results indicate that PFD prevents endotoxin-induced liver injury after hepatic ischemia-reperfusion, in part through the decrease of neutrophil infiltration to the liver.     

海藻糖对肝脏缺血再灌注损伤的保护作用及机制研究

目的探讨海藻糖是否对肝脏缺血再灌注损伤具有保护作用及其相关机制。方法C57BL/6J小鼠数字随机分为无缺血组、缺血再灌注组、海藻糖处理组和生理盐水对照组,缺血90 min后于再灌注的0h和6h,收集血液和肝组织,通过分离血清测丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)肝功能指标及肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-2(IL-2)炎症因子水平和肝组织病理改变研究海藻糖在肝脏缺血再灌注损伤中的作用;AML12小鼠肝细胞系构建缺糖缺氧-复糖复氧细胞模型,分为实验组和对照组,实验组根据给予的海藻糖浓度不同分为低剂量组和高剂量组,对照组无海藻糖,收集细胞,流式细胞仪检测凋亡水平以研究海藻糖对肝脏缺血再灌注损伤诱导的细胞凋亡的影响,蛋白印迹法检测Caspase-3、Cleaved Caspase-3和Bcl-2蛋白水平以研究海藻糖在肝脏缺血再灌注损伤诱导的细胞凋亡中的分子机制。结果体内动物实验显示肝脏缺血再灌注后,缺血再灌注组ALT、AST及TNF-α、IL-1β和IL-2等肝功能指标及炎症因子水平升高(P<0.05),且肝组织发生坏死;而在给予海藻糖处理后,ALT、AST、TNF-α、IL-1β和IL-2等水平较生理盐水对照组降低且肝组织坏死面积也减少(P<0.05)。体外细胞实验显示与对照组相比,实验组肝细胞凋亡水平下降;且实验组活化的促凋亡蛋白Cleaved Caspase-3水平下降、抗凋亡蛋白Bcl-2水平升高。结论在体内和体外条件下海藻糖对肝脏缺血再灌注损伤有保护作用,其机制可能是通过抑制肝脏缺血再灌注损伤诱导的炎症发生和抑制Caspase-3的活化并促进Bcl-2的表达,减轻细胞凋亡,从而保护肝脏缺血再灌注损伤。     

Protective effect of human urinary thrombomodulin on ischemia- reperfusion injury in the canine liver

This study was performed to determine whether human urinary soluble thrombomodulin plays a role in liver ischemia-reperfusion injury. Liver ischemia was induced in two groups of dogs. Group 1 was exposed to 60 min ischemia, and group 2 was exposed to 60 min ischemia after preischemic administration of human urinary soluble thrombomodulin. In group 1, the thrombin-antithrombin complex and hyaluronic acid were significantly elevated after ischemia, compared with the preischemic values. While liver issue blood flow and the plasmin-alpha(2)-plasmin inhibitor complex significantly decreased, AST, ALT and m-AST dramatically increased after reperfusion. In group 2, the increase in the thrombin-antithrombin complex and hyaluronic acid was significantly suppressed, and AST, ALT and liver tissue blood flow significantly improved, compared with group 1. Histologically, in group 2, the hepatic tissue structure, including endothelial cells, was relatively intact. These findings suggest that administration of thrombomodulin inhibits endothelial cell injury and coagulopathy and offers protection from liver ischemia-reperfusion injury.     

肝细胞凋亡在肝硬化大鼠肝缺血再灌注损伤中的意义

目的 研究肝硬化大鼠肝缺血再灌注（I／R）损伤和硬化肝比正常肝更容易损伤的机制是否与肝细胞凋亡有关？方法 建立原位肝I／R模型，将肝硬化大鼠随机分为2组：A组：缺血时间（I）＝20min;B组：I＝30min;C组：正常大鼠，I＝30min，比较灌注前后各组血清AST、ALT的变化和肝细胞凋亡的百分数。结果 肝硬化大鼠肝I／R后，AST、ALT明显升高，以灌注后6h为高峰，灌注24、72h后逐渐下降。灌注6h后，B组的血清转氨酶为3组中最高（P＜0．05），说明B组肝损伤最严重。肝细胞凋亡在I／R后明显增多，以灌注后6h为高峰，随后逐渐下降，变化与转氨酶一致。灌注后6h，B、A、C组肝细胞凋亡的百分数分别为20．9％、13．5％和10．7％，B组明显高于A、C两组（P＜0．01）。再灌注72h内未见明显肝细胞坏死。结论 肝细胞凋亡是肝硬化大鼠I／R损伤肝细胞死亡的主要形式，肝细胞凋亡与肝缺血时间密切相关，肝硬化肝细胞比正常肝细胞容易发生凋亡是硬化肝对缺血敏感的重要原因。     

大黄素对大鼠肝脏缺血再灌注损伤的预防作用

目的:探讨大黄素对肝脏缺血-再灌注损伤的保护作用及其机制.方法:将45只成年雄性SD大鼠随机分成三组:假手术对照组(A组)15只,肝缺血30 min、再灌注90min组(B组)15只,术前5 d给予大黄素灌胃60mg/(kg·d),5次 肝缺血30 min、再灌注90min(C组)15只;观察血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、透明质酸酶(HA)、肝组织丙二醛(MDA)含量的变化及肝脏组织病理学改变情况,同时测定各组大鼠胆汁流量情况.结果:C组与B组相比,MDA含量显著降低(P＜0.05),HA浓度明显降低(P＜0.01),胆汁流量显著增加(P＜0.01),同时C组的肝细胞功能明显改善,且肝脏超微结构改变也较轻.结论:大黄素对肝脏缺血-再灌注损伤具有保护作用,该作用与减轻肝脏缺血再灌注后脂质过氧化程度和肝窦内皮细胞损伤有关.     

缺血预处理减轻大鼠肝缺血再灌注损伤的免疫机制研究

目的探讨大鼠肝缺血再灌注损伤(HIRI)的免疫机制和缺血预处理(IPC)的保护作用。 方法80只大鼠被随机分为假手术组(A组)、肝门阻断20 min组(B组)、30 min组(C组)、40 min组(D组)以及肝门阻断30 min前预处理组(E组),每组再分为再灌注2 h亚组和24 h亚组,各8只。检测再灌注后2 h、24 h的血丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、白细胞介素10、12(IL-10、IL-12)以及外周血T淋巴细胞亚群的水平,观察再灌注后2 h、24 h时的存活率及肝脏病理情况。 结果随着肝门阻断时间的延长,ALT、AST显著升高,肝内炎症细胞浸润增加,24 h存活率逐渐降低。D组再灌注2 h时,CD8+ T淋巴细胞显著升高,CD4+/CD8+比值下降,调节性T淋巴细胞显著减少,血清IL-10显著降低,而IL-12水平显著升高。再灌注后24 h,B组大鼠各项指标逐步恢复至假手术组水平,而D组大鼠CD4+T淋巴细胞、CD4+/CD8+比值尤其是Treg显著升高,且IL-10水平显著升高,IL-12水平明显降低。与C组相比,E组阻断30 min后无一例死亡,再灌注2 h的ALT、AST水平显著降低,Treg和IL-10水平显著升高,IL-12水平明显降低,再灌注24 h后各项指标恢复并接近假手术组水平,肝脏病理损伤较轻。 结论肝缺血再灌注引起肝脏损伤甚至死亡,可能与诱导T淋巴细胞尤其是Treg和细胞因子的紊乱有关。缺血预处理可以增加再灌注早期的Treg细胞,有效纠正免疫紊乱,减轻损伤。     

入肝血流阻断和全肝血流阻断对肝组织氧压影响

目的 研究兔常温下入肝血流阻断（portal triad clamp,PTC)及全肝血流阻断（total hepatic vascular exclusion,THVE)对肝组织氧压（tissue oxygen pressure,Ptio2)的影响。方法 24只兔均分二组即PTC和THVE组。分别测定二组缺血前、缺血30min及再灌注30min后肝Ptio2值及血清丙氨酸氨基转氨酶（ALT）值变化。结果 PTC和THVE组均表现为肝Ptio2下降，但THVE较PTC组肝Ptio2值下降更显著（P＜0．01）、血清ALT值也明显升高（P＜0．05）。结论 PTC组较THVE组对肝缺血的耐受性增加。     

N-乙酰半胱氨酸预处理对肝脏缺血再灌注损伤的保护作用

目的 探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)预处理对肝脏缺血再灌注损伤的保护作用.方法 18 例肝血管瘤手术患者随机分为3 组(n=6):对照组(C0)、NAC 预处理组(PR)和NAC 后处理组(PO),其中PR和PO 组分别于肝门阻断前和开放后给予NAC 120 mg/kg.三组患者均于切皮前(T0)、肝门阻断开放后1 h(T1)及6 h(T2)抽血检测谷丙转氨酶活性(ALT)和谷草转氨酶(AST)水平,并于肝门阻断开放后1 h(T1)取肝组织测定丙二醛(MDA)含量及核因子κB(NF-κB)活性.结果 肝门阻断开放后1 h(T1)和6 h(T6),各组的ALT 和AST 水平均明显高于肝门阻断前(T0)水平(P<0.01);与对照组相比,PR 和PO 组的MDA 含量在肝门阻断开放后1 h(T1)明显减少(P<0.01),但NF-κB 的活性仅在PR 组显示有明显的降低(P<0.01).结论 NAC 预处理可有效防治肝脏缺血再灌注损伤,其机制与抑制再灌注后NF-κB 的启动激活有关.     

内质网应激分子伴侣GRP78在大鼠缺血再灌注损伤肝脏中的表达

目的:观察内质网应激相关分子葡萄糖调节蛋白78(GRP78)在大鼠缺血再灌注损伤肝脏组织中的表达水平.方法:将24只健康雄性SD大鼠随机均分为假手术组,单纯肝缺血组(肝缺血30 min+再灌注0h),再灌注6h组(肝缺血30 min+再灌注6h)和再灌注12h组(肝缺血30 min+再灌注12h).分别检测各组血清丙氨酸转氨酶(ALT)和门冬氨酸转氨酶(AST)水平;肝组织病理学、凋亡情况及GRP78 mRNA表达水平.结果:与对照组比较,各实验组大鼠肝缺血后出现明显的肝组织损伤,且随着再灌注时间的延长损伤加重,表现为血清ALT和AST水平升高,明显的肝组织病理学改变,肝细胞凋亡率增加,各组间计量指标的差异均有统计学意义(均P＜0.05).大鼠肝组织GRP78 mRNA变化趋势与上述指标一致,缺血后表达明显上调,且随着再灌注时间延长而逐渐升高,各组间差异均有统计学意义(均P＜0.05).结论:缺血再灌注损伤肝脏组织中GRP78表达上调,但其具体作用还有待于探明.     

七氟醚预处理对右肝癌切除患者肝脏缺血再灌注损伤的保护作用

目的：探讨七氟醚预处理对右肝癌切除患者肝脏缺血再灌注损伤的保护作用及其机制。方法：择期全麻下行右肝癌手术切除患者40例．ASAI或II级,术中经第一肝门阻断．血流阻断时间10～30min．随机分为2组（n=20）：缺血再灌注组（IR组）和七氟醚预处理组（S组）。两组麻醉维持期间均保持脑电双频谱指数40-50。s组麻醉诱导后吸入1MAC七氟醚（呼气末浓度）．30min后洗脱15min。于麻醉诱导前（T0）、缺血再灌注即刻（T1）、1h（T2）、6h（T3）抽血测血清中谷丙转氨酶（ALT）．谷草转氨酶（AST）,乳酸脱氢酶（LDH）的含量以及肝脏组织匀浆中丙二醛（MDA）含量和超氧化物岐化酶（SOD）活性,并行肝组织病理学观察。结果：与麻醉诱导前比较．两组缺血再灌注即刻．1h、6h血清ALT．AST,LDH含量均显著增加（P〈0．05）;与IR组比较,s组肝脏缺血再灌注后相应各时点血清ALT．AST、LDH含量均降低．肝组织匀浆MDA含量减少,SOD活性增加（P〈0．05）;肝组织病理学损伤减轻。结论：七氟醚预处理对右肝癌切除患者肝脏缺血再灌注损伤有保护作用．可能与其抑制氧自由基生成．减少脂质过氧化有关。     

L-carnitine could not improve hepatic warm ischemia-reperfusion injury despite ameliorated blood flow

BACKGROUND: Carnitine is applied to ameliorate ischemia-reperfusion (I/R) injury of several organs. However, application to hepatic I/R injury is not frequently reported. The aim of this study was to elucidate the effect of exogenous carnitine administration to ameliorate the warm hepatic I/R injury. MATERIALS AND METHODS: Male Wistar rats were divided into two groups, a carnitine group (Car);100 mg/kg of l-carnitine administration and a control group (C); vehicle administration. Thirty minutes after administration, the left hepatic lobes were given 60-min ischemia and then reperfused. Plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamate dehydrogenase (GLDH), tumor necrosis factor (TNF)-alpha, and lipoperoxides (LPO) were measured. Hepatic adenosine triphosphate (ATP) concentration was also measured. The hepatic blood flow was estimated using a Laser Doppler. The presence of apoptosis in the livers was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. RESULTS: In group Car, the blood flow of the left hepatic lobes was better recovered during the reperfusion period than in group C (P < 0.0001). Plasma levels of ALT, AST, GLDH, and TNF-alpha at 1 h after reperfusion were not significantly different between the groups. Although there were no statistical significances, ALT, AST, and TNF-alpha levels in group Car at 24 h after reperfusion tended to be higher than in group C. Plasma LPO levels were not different between the two groups. Also hepatic ATP concentration was not different between the two groups. TUNEL positive liver cells were visible only in group Car at 24 h after reperfusion, but not in the controls. CONCLUSIONS: Although carnitine administration improved the hepatic blood flow during the reperfusion period, we could not demonstrate a protective effect to the hepatic warm I/R injury.     

Important role for endothelins in acute hepatic ischemia/reperfusion injury.

The aim of this study was to explore the complex role of endothelins (ETs) in hepatic ischemia-reperfusion injury and to minimize this type of injury by nonselective ET receptor blockade. In an in vivo rat model, hepatic ischemia was induced for 30 min. The rats were divided into three groups: (1) sham operated, (2) untreated ischemic, and (3) group treated with the nonselective ET receptor antagonist bosentan (1 mg/kg body weight iv). Blockage of the ET system during ischemia-reperfusion was assessed by: (1) in vivo microscopic analysis, (2) measurement of local tissue PO2, (3) laser Doppler flowmetry, (4) transaminases, and (5) tumor necrosis factor (TNF)- serum levels. During liver ischemia, anoxia (mean liver pO2 decreased from 14.7 to 1.5 mm Hg) and TNF- (levels rose from 0 pg/mL to 145.3 pg/mL at the end ofischemia) were associated with the release of ETs. Immunoreactive ET-1 (ir-ET-1) plasma levels (basal levels: 12.1+/-1.8 pg/mL) went up by 2.6-fold (32.1+/-6.8 pg/mL) after 15 min and by 11.7-fold (142.1+/-32.6 pg/mL) after 120 min of reperfusion. Increased plasma levels of ir-ET-1 were associated with sinusoidal constriction to 77.6+/-7.1% of basal diameters. This constriction led to significant decreases in perfusion rate (77+/-3%), local tissue PO2 (6.9+/-2.7 mm Hg), and erythrocyte flux (61.7+/-13.8% of basal values). Hepatocellular damage, evaluated via the serum level of aspartate aminotransferase (AST, increase to 393.5+/-68.3 U/L, preoperative 23.9+/-2.0 U/L) was detectable 6 h after reperfusion (p < .05). Administration of bosentan before 30 min of ischemia significantly reduced ischemia-reperfusion injury and was associated with an increase of ir-ET-1 levels to 110.8+/-12.0 pg/mL and 94.1+/-25.0 pg/mL after 15 and 120 min of reperfusion. Sinusoidal diameters were maintained at nearly 100% in the treatment group instead of 77%, while perfusion rate (88+/-2%) and tissue PO2 (12.1+/-1.0 mm Hg) rose significantly in contrast with the nontreatment group (p < .05). Hepatocellular damage was reduced (AST levels after 6 h of reperfusion 244.0+/-34.4 U/L, p <.05), and leukocyte sticking and rolling were diminished (p < .01). In the treatment group, bosentan values of 5.6+/-0.7 and 2.9+/-0.4 ng/mL after 15 and 120 min of reperfusion were measured. In conclusion the release of endothelins is combined with microcirculatory disturbances and local hypoxia, thereby causing liver damage. By protecting the liver microcirculation, ET receptor blockade of both receptors at a low dose increased blood and oxygen supply to the liver and reduced hepatocellular injury. These results constitute the bases for further studies and transfer into clinical practice.     

Genistein预处理对大鼠肝缺血再灌注损伤的保护作用

目的：探讨genistein预处理对肝脏缺血再灌注损伤的保护作用及其机制。
方法：54只SD大鼠完全随机分成3组。A组为I/R组:70%热缺血60 min及再灌注;B组为I/R
 genistein（GST）预处理组;C组为假手术组。于成模后2,6,12 h取大鼠血清和肝组织,检测血清AST,ALT浓度和肝组织MDA浓度,免疫组化法检测肝组织casepase-3蛋白的表达,光镜下观察肝脏组织病理变化。
结果：与I/R组相比,genistein预处理血清中AST及ALT浓度明显降低,肝组织病理损伤明显减轻。肝组织casepase-3蛋白表达及MDA浓度显著降低（均P＜0.05）。
结论：genistein预处理对大鼠肝脏热缺血再灌注具有保护作用,其机制与清除氧自由基,抑制细胞凋亡有关。     

Protective Effect of MESNA (2-Mercaptoethane Sulfonate) Against Hepatic Ischemia/Reperfusion Injury in Rats

Purpose Reoxygenation of ischemic tissue generates various reactive oxygen metabolites (ROMs), which have a deleterious effect on various cellular functions. We evaluated the possible protective effect of 2-mercaptoethane sulfonate (MESNA) on hepatic ischemia/reperfusion (I/R) injury.Methods Wistar albino rats were subjected to 45-min hepatic ischemia, followed by 60-min reperfusion. 2-Mercaptoethane sulfonate, 150 mg/kg, or saline was given intraperitoneally (i.p.) twice, 15 min before ischemia and immediately before reperfusioin. We measured serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels to assess liver function. Liver tissue samples were taken to measure the levels of malondialdehyde (MDA), an end-product of lipid peroxidation; glutathione (GSH), a key antioxidant; and myeloperoxidase (MPO) activity, as an indirect index of neutrophil infiltration. We also measured hepatic collagen content, as a fibrosis marker.Results Plasma ALT and AST levels were higher in the I/R group than in the control group, but this increase was significantly decreased by MESNA treatment. Hepatic GSH levels, which were significantly depressed by I/R, increased back to the control levels in the MESNA-treated I/R group. Increases in tissue MDA levels and MPO activity caused by I/R injury decreased back to the control levels after MESNA treatment. Similarly, the increased hepatic collagen content in the I/R group decreased to the level of the control group after MESNA treatment.Conclusion The fact that MESNA alleviated I/R-induced injury of the liver and improved hepatic structure and function suggests that its antioxidant and oxidant scavenging properties may be of therapeutic value in protecting the liver against oxidative injury caused by I/R.     

P38 mitogen-activated protein kinase inhibition attenuates ischemia-reperfusion injury of the rat liver

BACKGROUND: Several studies have implicated the mitogen-activated protein kinase (MAPK) signal pathway in non-hepatic organ ischemia-reperfusion injury. However, the role of p38 MAPK in hepatic ischemia-reperfusion injury remains unclear. This study investigated the role of p38 MAPK in hepatic ischemia-reperfusion injury. METHODS: Male Sprague-Dawley rats were divided into 4 groups (sham, FR-only, control, and FR-treated groups). The animals in the control and FR-treated groups were subjected to 30 minutes of warm ischemia with congestion of the gut. The FR-only and FR-treated groups received FR167653 (FR), which is a novel p38 MAPK inhibitor. The serum levels of aspartate transaminase, alanine transaminase, lactate dehydrogenase, tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were measured (each, n = 6). Liver tissue blood flow was measured at pre-ischemia, end-ischemia, and 30, 60, 90, and 120 minutes after reperfusion (each, n = 4). The liver tissues in the control and FR-treated groups were excised for p38 MAPK and c-Jun N-terminal kinase (JNK) analyses and histopathology (each, n = 4). RESULTS: Serum levels of aspartate transaminase, alanine transaminase, lactate dehydrogenase, TNF-alpha, and IL-1beta were significantly lower in the FR-treated group than in the control group, and liver tissue blood flow was significantly higher in the FR-treated group than in the control group. Histopathologically, tissue damage was milder in the FR-treated group than in the control group. Both p38 MAPK and JNK were markedly phosphorylated after 30 minutes of reperfusion, and FR inhibited the phosphorylation of p38 MAPK without affecting the JNK. CONCLUSIONS: FR decreased serum TNF-alpha and IL-1beta levels and liver injury associated with the inhibition of p38 MAPK activation. These results suggest that inhibiting the activation of p38 MAPK may attenuate warm ischemia-reperfusion injury of the liver.