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【摘要】 目的 探讨乳化异氟醚预处理对大鼠肝脏缺血再灌注损伤的保护作用,并且证明这一作用由Kupffer细胞介导。方法 将SD大鼠制成肝脏缺血再灌注模型,随机分为脂肪乳剂对照组(C) 、Kupffer细胞阻断对照组(CK) 、乳化异氟醚预处理组(IPC)和Kupffer细胞阻断后乳化异氟醚预处理组(IK),观察肝脏缺血60min 再灌注2h 后血清中谷丙转氨酶(ALT) 、谷草转氨酶(AST)、肝细胞匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)和肝组织病理学改变。结果 C组、CK组和IK组肝脏缺血再灌注后血清ALT 和AST 含量显著升高,肝细胞匀浆MDA含量增高,SOD含量降低,肝组织病理学损害明显增加;而IPC组肝脏缺血再灌注后血清ALT 和AST 含量与前三组相比显著降低,肝细胞匀浆MDA含量减少,SOD含量增加,肝组织病理学损害明显减轻。结论 乳化异氟醚预处理对肝脏缺血再灌注损伤有保护作用,并且这一作用由Kupffer细胞介导。 【关键词】 Kupffer细胞;乳化异氟醚;缺血再灌注损伤 Kepffer cells mediated emulsified isoflurane precondition against hepatic ischemia and reperfusion injury in the rats LV Hao,YANG Li-qun,YU Wei-feng,REN Hong-mei,ZHU Min,XU Li-ya.Department of Anesthesiology,Eastern Hepatobiliary Surgical Hospital,the Second Military Medical University,Shanghai 200438,China. Corresponding author:YU Wei-feng 【Abstract】 Objective To investigate the protective effect of pretreatment with emulsified isoflurane on liver ischemia and reperfusion injury in rats. Methods A total of 32 healthy adult SD rats,weighing between 250 g to 300 g,were randomly divided into four groups: preconditioning with intralipid group (C , n = 8),inhibition of Kupffer cell and preconditioning with intralipid group (CK,n = 8), preconditioning with emulsified isoflurane group (IPC,n = 8), inhibition of Kupffer cell and preconditioning with emulsified isoflurane group (IK,n = 8). Rats suffered from ischemia for 30 min and were followed by reperfusion for 2 hours. The amimals were kill免费论文网 【http://www.51lunwen.net】ed at 2 hours after reperfusion. Serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined.Hepatic cell homogenate levels of MDA and SOD were determined. The histopathologic changes in the liver were also observed. Results Compared with those in C ,CK and IK groups,in IPC group serum levels of ALT and AST decreased significantly after liver ischemia and reperfusion. Hepatic cell homogenate levels of MDA decreased and SOD increased. The injury degrees of liver histopathology in IPC group was much less than that in C,CKand IK groups. Conclusion Pretreatment with emulsified isoflurane can protect liver from ischemia and reperfusion injury and this effect may mediated by Kupffer cells. 【Key words】 Kupffer cells; emulsified isoflurane; ischemia and reperfusion injury 最近的研究显示异氟醚等吸入麻醉药预处理对大鼠心、脑、肾、肺、脊髓早期的缺血再灌注损伤有保护作用,并且揭示了部分的作用机制[1-5] 。吸入麻醉药对肝脏的影响,过去研究大多集中在对肝脏的毒性作用,然而,吸入麻醉药可诱发肝脏的保护作用。在大鼠缺血再灌注及培养肝细胞缺氧复氧损害模型中,异氟醚、七氟醚和氟烷能减轻早期缺血再灌注或缺氧复氧损害[6-7]。异氟醚预处理对大鼠肝缺血再灌注损伤的保护作用目前国内外的研究不多,其机制的研究还处于起步阶段。本实验拟采用大鼠肝脏缺血再灌注模型,研究异氟醚预处理对肝脏缺血再灌注损伤的保护作用,以期为临床合理用药提供理论依据。 1 材料与方法 1. 1 研究对象 SD大鼠32只,雄性,质量250~300 g,由第二军医大学实验动物中心提供。将动物分为4组:脂肪乳剂对照组(C组, n =8),经大鼠尾静脉用微量泵给予脂肪乳剂预处理,剂量为30%脂肪乳剂(华瑞制药有限公司提供)6ml/kg/h,持续给药半小时,停药15分钟,然后进行缺血再灌注;Kupffer细胞阻断对照组(CK组, n =8) ,实验前24h大鼠腹腔注射Kupffer细胞特异性阻断剂氯化钆(10mg/kg),其余同C组;乳化异氟醚预处理组(IPC组, n =8),经大鼠尾静脉用微量泵给予乳化异氟醚预处理,剂量为8%乳化异氟醚6ml/kg/h,持续给药半小时,停药15分钟,然后进行缺血再灌注;Kupffer细胞阻断后乳化异氟醚预处理组(IK组, n =8) , 实验前24h大鼠腹腔注射Kupffer细胞特异性阻断剂氯化钆
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