Effects of inhalation anesthesia on hepatic metabolism, Kupffer cell activation and stress protein induction during ischemia-reperfusion

吸入麻醉对缺血再灌注时肝脏代谢、库普弗细胞活化及应激蛋白诱导的影响

基本信息

  • 批准号:
    07671645
  • 负责人:
  • 金额:
    $ 0.45万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    1995
  • 资助国家:
    日本
  • 起止时间:
    1995 至 1996
  • 项目状态:
    已结题

项目摘要

Although intraoperative ischemia/hypoxia-reperfusion/reoxygenation of the liver generally occurs under general anesthesia, little is known about the direct effect of volatile anesthetic agents on hepatic injury due to this phenomenon. The effect of volatile anesthetics on ischemia/hypoxia-reperfusion injury was studied using isolated liver perfusion.The liver was isolated from 24h-fasted, male Sprague-Dawley rats and perfused through the portal vein with a modified Krebs-Ringer bicarbonate solution in a recirculating perfusion-aeration system. Ischemia was induced by reducing the bascline perfusion pressure from 1.2 to 0.2 kPa followed by reperfusion to baseline level. Hypoxic perfusion was produced by decreasing the oxygen concentration in the gas mixture from 95% to 10% followed by reoxygenation at 95% oxygen. Viability of the liver was assessed by lactate dehydrogenase (LDH) release from the liver. To determine the effect of volatile anesthetics on the extracellular generation of su … More peroxide in the liver, the reduction of ferricytochrome c with or without superoxide dismutase was measured.Ischemia was evident by reduced oxygen delivery to the liver, and caused an increase in lactate production. Reperfusion caused a transient increase in lactate uptake and a significant increase in LDH release. Halothane, isoflurane and sevoflurane significantly attenuated LDH release during reperfusion. The suppression of LDH release was evident even when isoflurane was administered mainly during reperfusion period, but not when it was administered mainly during ischemia. These results indicate that volatile anesthetics may protect the fasted liver from carly, neutrophil-independent, ischemia reperfusion injury by acting during the reperfusion phase.LDH release was transiently but dramatically increased by reoxygenation and significantly attenuated by 1 and 2 minimum alvcolar concentrations of isoflurane. Suppression of Kupffer cells with gadolinium chloride also attenuated the LDH release. Isoflurane significantly reduced the superoxide generation on reperfusion. These results show that isoflurane protected the liver from early reoxygenation injury presumably mediated by Kupffer cells. The mechanisms of the inhibitory effect of isoflurane on the injury may involve suppression of extracellular superoxide generation during reoxygenation.Isolated rat livers with cell free perfusion were exposed to various periods of ischemia-reperfusion or hypoxia-reoxygenation. Hepatic oxygen consumption and alanine aminotransferase leakage from liver were determined during perfusion. The gene expression of heat shock protein 70, a major stress protein, of the liver was analyzed by Nothern blotting after perfusion. The expression of heat shock protein 70 mRNA augmented as the reperfusion period increased. The expression level after graded ischemia or hypoxia significantly correlated with the calculated hepatic oxygen bebt (r^2=0.737, p<0.001, n=21). These results suggest that accumulation of heat shock protein 70 mRNA reflects the severity of ischemia-reperfuion and hypoxia-reoxygenation injuries, and that stress response in reperfusion can be triggered without formed elements of blood.Altcrations in intracellular calcium homeostasis have been implicated in ischemia-reperfusion injuries. The effects of volatile anesthetics on the hemodynamic and metabolic alterations induced by the calcium ionophore A23187 were studied using isolated liver perfusion in fasted rats. Halothane, isoflurane and sevoflurane maintained basal hepatic flow, reduced oxygen consumption, and transiently enhanced net lactate production. All anesthetics significantly attenuated the decreases in hepatic flow and oxygen consumption after the administration of A23187. Volatile anesthetics may attenuate the hepatic vasoconstriction and oxygen debt induced by intracellular calcium overload. Less
虽然术中肝脏缺血/缺氧-再灌注/复氧通常发生在全身麻醉下,但由于这种现象,关于挥发性麻醉剂对肝损伤的直接影响知之甚少。采用离体肝脏灌流技术研究了挥发性麻醉药对大鼠肝脏缺血/缺氧再灌注损伤的影响。通过将基线灌注压从1.2 kPa降低至0.2 kPa,然后再灌注至基线水平来诱导缺血。通过将气体混合物中的氧浓度从95%降低至10%,然后在95%氧下再氧合来产生低通气灌注。通过从肝脏释放的乳酸脱氢酶(LDH)评估肝脏的活力。为了确定吸入麻醉药对细胞外生成sur的影响, ...更多信息 在肝脏中的过氧化氢,铁细胞色素C的减少与或不与超氧化物歧化酶进行了测量。缺血是明显的减少氧气输送到肝脏,并导致乳酸生产的增加。再灌注引起乳酸摄取的短暂增加和LDH释放的显着增加。氟烷、异氟醚和七氟醚显著减弱再灌注期间LDH的释放。即使主要在再灌注期间给予异氟醚,LDH释放的抑制也是明显的,但主要在缺血期间给予异氟醚时则没有。这些结果表明,吸入麻醉药可通过作用于再灌注期来保护禁食肝脏免受非依赖于麻醉药的急性缺血再灌注损伤,LDH释放在复氧时短暂但显著增加,而1和2个最低肺泡浓度的异氟醚可显著减弱LDH释放。用氯化钆抑制枯否细胞也减弱了LDH的释放。异氟烷显著减少再灌注时超氧化物的产生。这些结果表明,异氟烷保护肝脏免受早期复氧损伤,推测是由枯否细胞介导的。异氟醚抑制肝损伤的机制可能与抑制复氧过程中细胞外超氧阴离子的产生有关。在灌注过程中测定肝脏耗氧量和丙氨酸转氨酶从肝脏的渗漏。灌流后,通过Nothing印迹分析肝脏的主要应激蛋白热休克蛋白70的基因表达。热休克蛋白70 mRNA表达随再灌注时间延长而增加。分级缺血或缺氧后的表达水平与计算的肝氧平衡显著相关(r^2=0.737,p<0.001,n=21)。结果提示,热休克蛋白70 mRNA的表达反映了缺血再灌注损伤和缺氧再复氧损伤的严重程度,缺血再灌注应激反应可在无血液有形成分的情况下触发,细胞内钙稳态的改变与缺血再灌注损伤有关。采用离体肝脏灌流法研究了吸入麻醉药对钙离子载体A23187引起的血流动力学和代谢变化的影响。氟烷、异氟烷和七氟烷维持基础肝流量,减少耗氧量,并短暂增加净乳酸产生。所有麻醉药均显著减弱A23187给药后肝流量和氧耗的降低。挥发性麻醉药可减轻细胞内钙超载引起的肝血管收缩和氧债。少

项目成果

期刊论文数量(13)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kon S.Imai M.Inaba H: "Isoflurane attenuates early neutrophil-independent hypoxla reoxygenation injuries in the perfused liver in fasted rats" Anesthesiology. 86. 128-136 (1997)
Kon S.Imai M.Inaba H:“异氟烷可减轻禁食大鼠灌注肝脏中早期不依赖中性粒细胞的缺氧再氧合损伤”麻醉学。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Imai M.Kon S.Inaba H: "Effects of nalothane,isoflurane,sevcflurane on ischemia reperfusion injury in the perfused liver of tasted rats." Acta Anaesthesiol Scand. 40. 1242-1248 (1996)
Imai M.Kon S.Inaba H:“纳洛烷、异氟烷、七氟烷对尝味大鼠肝脏缺血再灌注损伤的影响。”
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
M.Imai,S.Kon H.Inaba: "Effects of halothane,isoflurane and sevoflurane on ishemia-reperfusion injury in the perfused liver of fasted rats" Acta Anaesthesiol Scand. 40. 1242-1248 (1996)
M.Imai,S.Kon H.Inaba:“氟烷、异氟烷和七氟烷对禁食大鼠灌注肝脏缺血再灌注损伤的影响”Acta Anaesthesiol Scand。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Araki M.Inaba H.et al: "Effects of volatile anesthetics on the calcium ionuphore A23187 mediated alterations in hepatic flow and metaholism" Acta Anaesthesiol Scand. 41. 55-61 (1997)
Araki M.Inaba H.等人:“挥发性麻醉剂对钙离子载体 A23187 介导的肝血流和代谢改变的影响”Acta Anaesthesiol Scand。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Imai M,Kon S and Inaba H: "Effects of halothane, isoflurane and sevoflurane on ischemia-reperfusion injury in the perfused liver of fasted rats." Acta Anaesthesiol Scand. volume 40. 1242-1248 (1996)
Imai M、Kon S 和 Inaba H:“氟烷、异氟烷和七氟烷对禁食大鼠灌注肝脏缺血再灌注损伤的影响”。
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    0
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INABA Hideo其他文献

INABA Hideo的其他文献

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{{ truncateString('INABA Hideo', 18)}}的其他基金

Control of sepsis with heat shock protein induced by high PEEP
高 PEEP 诱导的热休克蛋白控制脓毒症
  • 批准号:
    17591885
  • 财政年份:
    2005
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Development of High-density Heat Storage and Application Method of Latent Heat Emulsion Slurry for Energy Conservation.
高密度蓄热开发及潜热乳化浆节能应用方法。
  • 批准号:
    13450084
  • 财政年份:
    2001
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Study of mechanism and condition for ischemic preconditioning induced by volatile anesthetics pretreatment in the liver
挥发性麻醉药预处理引起肝脏缺血预适应的机制和条件研究
  • 批准号:
    12470314
  • 财政年份:
    2000
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of Fluidized Bed Heat Exchanger Using Organic Powder
有机粉末流化床换热器的研制
  • 批准号:
    10558073
  • 财政年份:
    1998
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Study on the role of lymphocytes on organ failure and disturbed host defense mechanism due to infection and stress
淋巴细胞在感染和应激引起的器官衰竭和宿主防御机制紊乱中的作用研究
  • 批准号:
    09470324
  • 财政年份:
    1997
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
A Study on Heat Storage and Heat Transportation Characteristics of Water Solution of Micro-capsule Including Phase Change Material
相变材料微胶囊水溶液储热传热特性研究
  • 批准号:
    08455106
  • 财政年份:
    1996
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Heat and mass transfer of ice water slurry made by flowing supercooled water solution
过冷水溶液流动形成的冰水浆的传热传质
  • 批准号:
    07555386
  • 财政年份:
    1995
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
AUGMENTATION OF DEFROSTING BY USE OF ACTIVATION PHENOMENON OF ICE CRYSTAL WITH IRRADIATED INFRARED RAYS
利用红外线照射下冰晶的激活现象增强除霜效果
  • 批准号:
    06650249
  • 财政年份:
    1994
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
Role of Protein Kinase C in the Regulation of Hepatic Flow and Metabolism in the Perfused rat liver
蛋白激酶 C 在灌注大鼠肝脏中肝血流和代谢调节中的作用
  • 批准号:
    05671249
  • 财政年份:
    1993
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)
A Study of Snow Melting Mechanism by Solar Radiative Absorption Material
太阳辐射吸收材料融雪机理研究
  • 批准号:
    62550141
  • 财政年份:
    1987
  • 资助金额:
    $ 0.45万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

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缺氧诱导因子(HIF)-2α转录抑制树突状细胞CD36表达减轻肾脏缺血再灌注损伤的机制
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    82371142
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肢体缺血后适应抑制肺泡巨噬细胞活化及防治肺缺血再灌注损伤机制的研究
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    2010
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A novel treatment for REBOA complications: Hydrogen gas inhalation therapy to alleviate oxidative stress due to ischemia-reperfusion injury
REBOA并发症的新型治疗方法:氢气吸入疗法减轻缺血再灌注损伤引起的氧化应激
  • 批准号:
    23K21458
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    2024
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    $ 0.45万
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Development ofsynthetic heparin to protect liver graft from ischemia reperfusion injury duringtransplantation
开发合成肝素以保护移植肝免受移植过程中的缺血再灌注损伤
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    10759102
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    2023
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    $ 0.45万
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Nanowired human isogenic cardiac organoids to treat acute myocardial ischemia/reperfusion injuries
纳米线人类同基因心脏类器官治疗急性心肌缺血/再灌注损伤
  • 批准号:
    10721208
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    2023
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Nck1 in Ischemia Reperfusion Injury
Nck1在缺血再灌注损伤中的作用
  • 批准号:
    10715406
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    2023
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The Role of Neutrophils in Ischemia/Reperfusion Injury following Acute Stroke
中性粒细胞在急性中风后缺血/再灌注损伤中的作用
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    10606952
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    2023
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Efficacy of Transmaternal Human Cord Blood Cell Transplantation Therapy for Fetal Tissue Damage Caused by Ischemia-Reperfusion
经母体人脐带血细胞移植治疗缺血再灌注引起的胎儿组织损伤的疗效
  • 批准号:
    23K07314
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    2023
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Zinc Protection Against Ischemia-Reperfusion Injury in Heart
锌可预防心脏缺血再灌注损伤
  • 批准号:
    10652915
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    2023
  • 资助金额:
    $ 0.45万
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Ischemia/Reperfusion injury and Myocardial edema
缺血/再灌注损伤和心肌水肿
  • 批准号:
    10718260
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    2023
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    $ 0.45万
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Role of Gasdermin D/E in intestinal ischemia-reperfusion injury
Gasdermin D/E 在肠缺血再灌注损伤中的作用
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    23K15529
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    2023
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    Grant-in-Aid for Early-Career Scientists
Deficiency Of Hedgehog Interacting Protein (Hhip) In Endothelial Cells Prevents Renal Ischemia Reperfusion -Induced Renal Tubular Cell Injury via the inhibition of NF-KB signaling
内皮细胞中 Hedgehog 相互作用蛋白 (Hhip) 的缺乏可通过抑制 NF-KB 信号传导来防止肾缺血再灌注引起的肾小管细胞损伤
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    495595
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    2023
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