谷氨酰胺与肝脏缺血再灌注损伤

谷氨酷胺（Glutamine,Gln）为L-谷氨酸的γ-羧基酰胺化物,是体内含量最丰富的非必需氨基酸。50年代研究发现,Gln是培养细胞分化增殖所必需的营养物质,Windmueller等在1978年首次揭示,Gln是生理状态下小肠的主要氧化燃料和供能物质,而近来有关其在肝脏与小肠缺血再灌注损伤中的作用,已成为研究热点。     

亚甲蓝对兔肝缺血再灌注损伤的影响

目的 探讨亚甲蓝对兔肝缺血再灌注损伤的影响.方法 健康成年新西兰大白兔24只,雌雄不拘,体重2.0～2.3 kg,随机分为3组(n=8):假手术组(S组)、肝缺血再灌注组(I/R组)和亚甲蓝组(MB组).I/R组及MB组采用夹闭肝左外叶、中叶、右中叶及方形叶肝动脉分支40min再灌注60 min的方法制备肝缺血再灌注模型,S组仅游离相应血管.MB组于再灌注前20 min经耳缘静脉注射亚甲蓝5 mg/kg(用生理盐水稀释至5 ml),S组及I/R组给予等容量生理盐水.于缺血前即刻(T1)、缺血20 min(T2)、加min(T3)、再灌注1 min(T4)、再灌注5 min(T5)、30 min(T6)、60 min(T7)时记录MAP和HR.于T1,5-7时取股动脉血样1 ml,测定血清TNF-α及IL-6的浓度.分别于T1,6,7时取股动脉血样1.5 ml,测定血浆ALT及AST的活性.于T7时测定肝左叶组织SOD活性及MDA含量,光镜下观察肝组织病理学结果.结果 与S组比较,I/R组T4-7,时MAP降低,T7时HR降低,肝组织SOD活性降低,MDA含量升高,I/R组及MB组T3-5时血清TNF-α和IL-6浓度升高,T6,7时血浆ALT和AST活性升高(P<0.05或0.01);与I/R组比较,MB组T4-7时MAP升高,肝组织SOD活性升高,MDA含量降低,T3-5时血清TNF-α和IL-6浓度降低,T6,7时血浆ALT和AST活性降低(P<0.05或0.01).MB组肝组织损伤较I/R组减轻.结论 亚甲蓝可维持血液动力学稳定,减轻兔肝缺血再灌注损伤.     

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.     

HHI-I对大鼠肝缺血再灌注损伤的影响

目的:研究活血化瘀注射液I号(HHI-I)对大鼠肝脏缺血再灌注(IR)损伤的影响,并与缺血预处理(IP)比较作用的效果。方法:清洁级健康雄性SD大鼠80只,随机分为4组(Sham组,IR组,IP组,HHI-I组),测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)的水平;取左肝测组织丙二醛(MDA)、超氧化物歧化酶(SOD)的含量。结果:IR组、IP组、HHI-I组的ALT、AST、LDH活性均明显高于Sham组(P<0·01),再灌注后SOD值均下降,各组各时间点与Sham组比较均具有统计学差异(P<0·05)。再灌注后MDA值均升高,缺血再灌注后6h升至最高点(P<0·01),且各时间点预处理组均低于IR组(P<0·05),HHI-I组MDA(3h、6h)明显低于IP组(P<0·05)。结论:大鼠肝脏缺血再灌注后造成了明显的肝脏损伤,IP与HHI-I预处理均可改善IR对肝脏造成的损伤,且后者效果优于前者。     

己酮可可碱对肝缺血和再灌注损伤的影响

己知己酮可可碱可改善组织氧合作用和恢复出血性休克后肝细胞功能，但对肝缺血和再灌注损伤的作用不甚清楚。为此，作者在4组可逆性肝缺血和再灌注损伤猪模型进行实验。在麻醉下正中切口过腹，游离门静脉、肝动脉及其胃十二指肠支和肝下皮下腔静脉，结扎分出肝总和肝左动脉支的胃血管。给肝素300ti／kg，在颈静脉插管。错夹肝动脉、胃十二指肠复和门静脉，肠系膜血流经导管回流至颈静脉插管。扔1组5只猪，在麻醉诱导前1小时灌入口服用己酮呼可碱24mg／kg（溶于3ml）橄榄油中；第2组5只猪，给口服用已酮可可碱50mg／kg；第3组9只闻，于再灌注…     

HHI-Ⅰ对大鼠肝缺血再灌注损伤的影响

目的：研究活血化瘀注射液Ⅰ号（HHI-Ⅰ）对大鼠肝脏缺血再灌注（IR）损伤的影响,并与缺血预处理（IP）比较作用的效果.方法：清洁级健康雄性SD大鼠80只,随机分为4组（Sham组,IR组,IP组,HHI-Ⅰ组）,测血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、乳酸脱氢酶（LDH）的水平;取左肝测组织丙二醛（MDA）、超氧化物歧化酶（SOD）的含量.结果：IR组、IP组、HHI-Ⅰ组的ALT、AST、LDH活性均明显高于Sham组（P＜0.01）,再灌注后SOD值均下降,各组各时间点与Sham组比较均具有统计学差异（P＜0.05）.再灌注后MDA值均升高,缺血再灌注后6 h升至最高点（P＜0.01）,且各时间点预处理组均低于IR组（P＜0.05）,HHI-Ⅰ组MDA（3 h、6 h）明显低于IP组（P＜0.05）.结论：大鼠肝脏缺血再灌注后造成了明显的肝脏损伤,IP与HHI-Ⅰ预处理均可改善IR对肝脏造成的损伤,且后者效果优于前者.     

再灌注初期控制性降压对肝叶切除术病人肝缺血再灌注损伤的影响

目的 评价再灌注初期控制性降压对肝叶切除术病人肝缺血再灌注损伤的影响.方法 择期行肝叶切除术病人40例,性别不限,年龄30～60岁,体重40～70kg,ASA分级Ⅱ或Ⅲ级,将病人按分层随机方法分为2组(n=20),对照组(C组)开放肝门后10 min期间维持MAP 75～100mm Hg,控制性降压组(H组)于开放肝门前2 min开始静脉输注硝酸甘油3～6μg·kg-1·min-1实施控制性降压,再灌注10 min期间维持MAP 60～70 mm Hg.分别于缺血前(基础状态)、缺血15 min和再灌注25min时采集静脉血样,测定血浆内皮素(ET)、一氧化氮(NO)、TNF-α和IL-1的浓度.结果 与基础值比较,两组缺血15 min和再灌注25min时血浆ET、TNF-α和IL-1的浓度升高,血浆N0浓度降低(P＜0.05);与C组比较,H组再灌注25min时血浆ET、TNF-α和IL-1的浓度降低,血浆NO浓度升高(P＜0.05).结论 再灌注初期控制性降压10 min可减轻肝叶切除术病人肝缺血再灌注损伤,其机制与调节肝窦内皮细胞ET和NO的平衡及抑制炎性反应有关.

Abstract：

Objective To evaluate the effect of controlled hypotension at the beginning of reperfusion on ischemia-reperfusion (I/R) injury of the liver in patients undergoing hepatectomy. Methods Forty ASA Ⅱ or Ⅲ patients aged 30-60 yr weighing 40-70 kg undergoing elective partial hepatectomy for liver cancer were randomly divided into 2 groups ( n = 20 each): group C normal BP and group H controlled hypotension. Hepatic portal was occluded during operation. In group C normal BP was maintained during reperfusion while in group H controlled hypotension (MAP was maintained at 60-70 mm Hg) was performed for 10 min since the beginning of reperfusion.Venous blood samples were taken before hepatic ischemia (T0 ,baseline) and at 15 min of ischemia (T1) and 25 min of reperfnsion (T2 ) for determination of plasma endothelin (ET), nitric oxide(NO), TNF-α and IL-1 concentrations. Results I/R of the liver led to significant increase in plasma ET, TNF-α and IL-1 concentrations and decrease in plasma NO concentration at T1,2 as compared with the baseline values at T0 in both groups. Plasma ET,TNF-α and IL- 1 concentrations were significantly lower while plasma NO concentration was significantly higher at T2 in group H than in group C. Conclusion Ten minutes controlled hypotension in the initial stage of reperfusion can attenuate I/R-induced injury to the liver in patients undergoing hepatectomy by balancing ET with NO and inhibiting inflammation response.     

褪黑素与肝缺血再灌注损伤

本文总结了近10年来国内外在肝缺血再灌注损伤方面各研究方向的分布情况，结合目前在药理、毒理、免疫学等方面研究的新热点褪黑素（melatonin,Mel)，并将其在最近几年应用于缺血再灌注损伤方面的研究进展作一系统性的回顾,概括了有关Mel与再灌注损伤研究各方向上的结合情况，从而初步阐述了该交叉领域的研究情况、方向以及存在的问题。     

异丙酚对肝叶切除术患者肝缺血再灌注损伤的影响

目的 探讨异丙酚对肝叶切除术患者肝缺血再灌注损伤的影响.方法 拟行肝叶切除术的肝癌患者60例,年龄28～64岁,体重50～77 kg,ASA Ⅰ～Ⅲ级,随机分为对照组(Ⅰ组)和异丙酚组(Ⅱ组),每组30例.Ⅱ组肝门开放后静脉输注异丙酚4～6 mg·kg-1·h-1至术毕.分别于麻醉前(T1)、肝门阻断前(T2)、肝门阻断后15 min(T3)、肝门开放后10 min(T4)和45 min(T5)时抽取中心静脉血测定血清谷草转氨酶(AST)、谷丙转氨酶(ALT)、超氧化物歧化酶(SOD)活性,丙二醛(MDA)浓度.结果 与T1时比较,两组T3-5时AST、ALT活性升高,Ⅰ组T4,5时SOD活性降低、MDA浓度升高,Ⅱ组T4,5时SOD活性升高、MDA浓度降低(P<0.05);与Ⅰ组比较,Ⅱ组T4,5时AST、ALT活性降低,SOD活性升高、MDA浓度降低(P<0.05).结论 肝门开放后至术毕静脉输注异丙酚4～6mg·kg-1·h-1可减轻肝叶切除术患者肝缺血再灌注损伤.     

丙泊酚与肝脏缺血/再灌注损伤

缺血/再灌注对肝脏造成损伤.众多资料显示丙泊酚对肝脏缺血/再灌注损伤有保护作用,这一保护作用与其抗氧化,阻断钙超载,减轻炎性细胞导致的损伤有关.肝脏缺血/再灌注也影响了丙泊酚的代谢.     

Effects of ischemic liver preconditioning on hepatic ischemia/reperfusion injury in the rat

To minimize bleeding during major liver resections or liver transplantation, surgical measures have been adopted that induce ischemia-reperfusion injury (I/R) which may significantly contribute to morbidity and mortality of partial liver resections. Several methods have sought to minimize I/R hepatic lesions. The present project assessed the protective role of ischemic preconditioning (IPC) in rat livers. The IPC was accomplished by clamping the hepatic pedicle for 5 minutes, followed by a 5-minute reperfusion (R) period before a 2-hour ischemia. Thereafter, reperfusions of 1, 3, and 24 hours were compared among IPC and control groups without IPC. Liver biopsy and blood samples were measured for mitochondrial respiratory control ratio (RCR), serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT). IPC protected liver mitochondrial function. Serum aminotransferase levels were significantly lower among animals undergoing IPC compared with groups without IPC. Thus, we verified the effects of IPC for hepatocellular protection against I/R lesions.     

Role of leukotrienes on hepatic ischemia/reperfusion injury in rats

BACKGROUND: Leukotrienes (LT), composed of cysteinyl LT (cLT; LTC(4), LTD(4), and LTE(4)) and LTB(4), are potent lipid mediators enhancing the vascular permeability and recruitment of neutrophils, which are common features of hepatic ischemia/reperfusion (I/R) injury. The aim of this study was to investigate whether LT can mediate the liver and lung injuries following hepatic I/R. MATERIALS AND METHODS: Sprague-Dawley rats were subjected to 90 min of partial hepatic ischemia followed by 3, 12, and 24 h of reperfusion. In the hepatic and pulmonary tissues, LT content and the mRNA expression of LT-synthesis enzymes, 5-lypoxygenase (5-LO), LTC(4) synthase (LTC(4)-S), and LTA(4) hydrolase (LTA(4)-H) were measured. Tissue injuries were assessed by plasma ALT, histological examination, and wet-to-dry tissue weight ratios. RESULTS: The cLT content in the hepatic tissue after 12 and 24 h reperfusion was increased 4- to 5-fold compared to controls and this was accompanied by the enhancement of hepatic edema and plasma ALT elevation. There were no significant changes in the mRNA expression of LT-synthesis enzymes in both tissues. LTB(4) levels were not increased despite a significant neutrophil infiltration in both tissues. CONCLUSIONS: These data suggest that cLT are generated in the liver during the reperfusion period and may contribute to the development of hepatic edema and exert cytotoxicity. Factors other than LTB(4) may contribute to neutrophil infiltration.     

肝硬变大鼠肝脏缺血再灌注损伤

为比较硬化肝与正常肝在缺血再灌注损伤时的差异和意义。作者采用四氯化碳复制大鼠肝硬变模型,通过大鼠肝脏缺血再灌注损伤模型,检查不同时限大鼠门静脉血内毒素、肝静脉血一氧化氮。结果显示：肝硬变大鼠再灌注时门静脉内毒素水平更高;肝脏ＮＯ合成释放显著增加。作者认为肝硬变时对缺血再灌注损伤反应与正常大鼠不同,可能是肝硬变时对缺血再灌注损伤更敏感,更易发生肝功能衰竭的重要原因。     

肝脏热缺血再灌注损伤对胆道系统的影响

肝移植已经成为治疗终末期肝病的重要手段而广泛应用于临床,但是胆道并发症尤其是缺血型胆道病变已成为影响患者长期生存和生活质量的重要因素.本文就近年来肝脏缺血再灌注引发胆道系统损伤的发生机制及其研究进展作一综述.     

培高利特对前脑缺血/再灌注损伤的影响

海马CA1区对脑缺血最为敏感,即使短暂的脑缺血也可造成锥体细胞凋亡。我们的前期研究发现,多巴胺D：受体激动剂培高利特（pergolide）可显著减轻沙土鼠脑缺血／再灌注损伤后行为学异常,减少海马CA1区锥体细胞凋亡,其脑保护作用与诱导bcl-2并抑制bax基因的表达有关。既往研究表明,脑缺血后c-jun表达的增高与细胞凋亡密切相关。本实验应用HE染色法、DNA原位末端标记（TUNEL）法及免疫组织化学染色方法,观察对沙土鼠前脑缺血再灌注后海马CA1区神经元凋亡和c-jun表达的影响,探讨培高利特发挥脑保护作用的基因调控机制。     

肝缺血再灌注后肺损伤机制及乌司他丁保护作用的实验研究

目的 研究肝缺血再灌注后肺损伤的机制以及乌司他丁的保护作用.方法 新西兰白兔24只,随机分为3组,每组8只.假手术组：麻醉后分离肝门,游离肝动静脉,关腹,120 min后处死.缺血再灌注组：夹闭左侧叶、左中央叶、右中央叶的血管,缺血60 min后再灌注60 min后立即处死.乌司它丁组同缺血再灌注组制作部分肝缺血再灌注模型,但于阻断前15 min注射乌司它丁2万U/kg.测定阻断前（T0）、阻断50min（T1）、再灌注10min（T2）、再灌注60min（T3）四个时点动脉血压、动脉血血气分析和TNF-α、IL-8水平.肝肺病理切片光镜观察、肺干湿重比、肺灌洗液蛋白含量及磷脂水平、肺组织丙二醛（MDA）含量、超氧化物歧化酶（SOD）活力、髓过氧化物酶（MPO）活力、肺组织SP-A mRNA及SP-A蛋白表达水平.结果 病理结果显示,乌司它丁组缺血再灌注肺损害较轻.缺血再灌注组和乌司它丁组pH阻断后降低,TNF-α和IL-8升高,TNF-α、IL-8水平、干湿重比、MDA、MPO高于假手术组,灌洗液蛋白浓度、PC、PG含量、SOD、SP-A蛋白表达低于假手术组（P＜0.05）,而乌司它丁组各项结果要好于缺血再灌注组（P＜0.05）.结论 肝缺血再灌注会导致肺损伤,缺血前给予乌司它丁可以减轻肺损伤.