异丙酚对兔肝缺血再灌注损伤保护作用及部分生化指标的影响

作者:罗遥,周党军,吕毅,景桂霞,肖颖。

【关键词】 二异丙酚;肝;再灌注损伤;琥珀酸脱氢酶;腺苷三磷酸。

Protective role of propofol against hepatic ischemiareperfusion injury and its effect on some biochemical indicators in rabbits。

【Abstract】 AIM: To investigate the protective role of propofol against hepatic ischemiareperfusion injury (HIRI) and the effect of propofol on some biochemical indicators in rabbits in vivo. METHODS: Forty rabbits were randomly divided into 4 groups with 10 animals each. They were HIRI model group(group A), HIRI plus 2 mL/(kg・h) normal sodium group(group B), HIRI plus 8 mg/(kg・h) propofol group (group C), and sham operation group (group D). The activity of succinodehydrogenase (SDH), ATP content in hepatic tissue and serum alanine aminotransferase (ALT), aspartate aminotransferase( AST) content were assayed after reperfusion for 30 min and 60 min. RESULTS: SDH activity in hepatic tissue in group A and B decreased significantly compared with that in group D(P0.05) and there was no difference between group C and D(P0.05) after reperfusion for 30 min and 60 min; ATP content in hepatic tissue decreased in group A,B,C compared with group D(P0.05), but the decreased degree of group C was much smaller than group A and B at the same time(P0.05);serum ALT,AST levels increased in group A,B,C compared with group D(P0.01, P0.05). CONCLUSION: Propofol can enhance the activity of SDH in mitochondria during ischemiareperfusion and increase the ATP content in hepatic tissue,thus showing the protective effect against HIRI.

【Keywords】 propofol; liver; reperfusion injury; succinate dehydrogenase; adenosine triphosphate。

【摘要】 目的: 探讨麻醉药异丙酚对兔在体肝脏缺血灌注损伤(HIRI)保护作用及部分生化指标的影响. 方法: 40只家兔随机分为四组,每组10只,分别为缺血灌注组(A组),缺血灌注生理盐水2 mL/(kg・h)组(B组), 缺血灌注异丙酚8 mg/(kg・h)组(C组)和假手术对照组(D组). 各组于再灌注后30 min及60 min时测定组织琥珀酸脱氢酶(SDH)活性、ATP含量以及血清谷丙转氨酶(ALT),谷草转氨酶(AST)的含量. 结果: 再灌注后30 min及60 min时,A,B两组肝组织中SDH活性与D组比较明显降低(P0.05),C组与D组比较无统计学差异(P0.05);A,B,C组肝组织中ATP含量与D组比较均降低(P0.05),但C组的降低程度小于同时间点的A,B两组(P0.05);A,B,C组血清ALT,AST水平均高于D组 (P0.01, P0.05). 结论: 异丙酚能增强缺血灌注时肝细胞线粒体中SDH的活力,增加肝组织中ATP的含量,对HIRI有保护作用.

【关键词】 二异丙酚;肝;再灌注损伤;琥珀酸脱氢酶;腺苷三磷酸。

0引言。

肝脏缺血灌注损伤(hepatic ischemiareperfusion injury, HIRI)机制复杂,以往大量研究证明与氧自由基(OFR)损害、线粒体功能异常、能量代谢障碍、钙离子超载、微循环障碍、中性粒细胞浸润、内毒素作用等因素有关. 本实验通过建立家兔HIRI模型,观测麻醉药异丙酚对肝细胞线粒体中SDH活力的影响,对缺血灌注组织中ATP含量的影响,以及ALT和AST水平的变化,旨在探索异丙酚对在体HIRI的保护作用及机制,为临床肝移植术中应用异丙酚麻醉和保护移植肝功能提供理论依据.

1材料和方法。

1.1材料西安交通大学医学院动物中心提供健康雄性家兔40只,兔龄6 mo左右,体质量2.0~2.5 kg,随机分为4组,每组10只. A组为缺血灌注组,B组缺血灌注生理盐水组,C组缺血灌注异丙酚组,D组假手术对照组.术前12 h禁食,自由饮水.

1.2方法。

1.2.1麻醉与模型建立将各组兔用30 g/L戊巴比妥钠(1.0 mL/kg)耳缘静脉缓慢注射麻醉后,仰卧固定于手术台上. 行颈内动脉插管,持续监测平均动脉压(MAP),并行同侧颈内静脉置管,接肝素帽待用. A,B,C实验组经兔上腹部正中切口,暴露肝门,用无损伤动脉夹钳闭肝门,完全阻断肝血流30 min后除去动脉夹实施再灌注,再灌注后30 min, 60 min取标本待测. D组只手术而不用动脉夹钳闭肝门.

1.2.2用药B,C两组由微量注射泵经颈内静脉分别持续输注生理盐水2 mL/(kg・h)和异丙酚8 mg/(kg・h) 直至术毕.异丙酚为瑞典AstraZeneca S.P.A.生产制造(200 mg/支).

1.2.3肝组织中SDH活性和ATP含量测定各组分别于再灌注后30, 60 min时取左外叶肝组织少许,生理盐水洗去血液,中性滤纸吸干,准确称取肝组织0.2 g,冰浴中制成匀浆,分别按试剂盒步骤,测定SDH活性和ATP含量.

1.2.4下腔静脉血ALT, AST含量测定各组分别于再灌注后30, 60 min时经下腔静脉抽取静脉血4 mL左右,置于37℃水浴箱中1 h,血液凝固后3000 r/min,4℃离心10 min分离血清,—70℃保存备用,全自动生化分析仪测定.统计学处理: 实验结果以x±s表示,使用SPSS11.5统计学软件进行分析处理. 组间比较采用单因素方差分析及LSDt两两比较,P0.05为差异有统计学意义.

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