机构地区:[1]徐州医学院附属医院,江苏省徐州市221002 [2]南京医科大学第一附属医院
出 处:《中华器官移植杂志》2010年第5期300-303,共4页Chinese Journal of Organ Transplantation
基 金:基金项目:国家自然科学基金(30671992)
摘 要:目的探讨依达拉奉减轻大鼠小体积肝移植物缺血再灌注损伤的作用及其可能机制。方法采用成年雄性SD大鼠作为肝移植的供、受者,随机将受者分为依达拉奉组和对照组,每组8只。依达拉奉组受者移植前30min经阴茎背静脉注射依达拉奉3mg/kg,对照组受者仅给予等量生理盐水。采用改良的二袖套法建立大鼠40%(供肝重量与受者全肝重量比)小体积供肝肝移植模型。术后6h时,处死两组受者,使用全自动生化分析仪检测血清天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平,采用酶联免疫吸附试验(ELISA)法检测移植肝组织中肿瘤坏死因子a(TNF-α)含量,使用相应的检测试剂盒检测移植肝组织中MDA含量以及SOD和MPO的活性。同时,取移植肝组织进行病理学检测,观察肝组织病理损伤情况。结果术后6h,依达拉奉组受者血清AST和ALT水平分别为(825.50±72.87)U/L和(687.40±72.21)U/L,对照组分别为(1188.03±124.04)U/L和(988.66±91.07)U/L,依达拉奉组明显低于对照组,两组间比较,差异均有统计学意义(P〈0.01)。与对照组比较,依达拉奉组受者移植肝组织中MDA和TNF-α含量明显下降,MPO活性也明显下降,而SOD活性则明显增加,两组间比较,差异均有统计学意义(P〈0.01)。移植肝组织病理学检查发现,对照组肝细胞发生明显的空泡样变性伴局部坏死灶,肝小叶结构破坏,门脉周围水肿、充血,炎症细胞浸润明显;依达拉奉组肝损伤明显减轻,小叶结构保存完整,肝细胞变性、坏死轻微,炎症细胞浸润明显减少。结论依达拉奉能够明显减轻大鼠小体积肝移植物缺血再灌注损伤,其机制可能与增强抗氧化能力、抑制脂质过氧化以及减轻炎症反应密切相关。Objective To investigate the protective effect of edaravone against ischemiareperfusion injury in small-for-size rat liver grafts and its possible mechanisms. Methods 40 % smallfor-size rat liver transplantation model was established by using modified two-cuff technique, adult male SD rats were used as donors and recipients, and 16 recipient rats were randomly divided into two groups (8 cases in each group): saline control group (control group) and edaravone treatment group (ED group). In the ED group, 3 mg/kg edaravone was given intravenously via penile vein 30 min before transplantation in the recipients. The same amount of saline was given in the control group at the same time points. Serum hepatic function (AST and ALT) and histopathological changes were analyzed; the contents of MDA and SOD, and hepatic myeloperoxidase (MPO) activity in liver grafts after 6 h were determined; and TNF-α levels at 6th h after reperfusion were measured by using enzyme-linked immunosorbent assay (ELISA method). Results As compared with control group, serum AST and ALT levels were significantly reduced at the 6th h after reperfusion in ED group (AST: 825.50 ± 72. 87 vs 1188. 03 ±124. 04; ALT.. 687. 40 ± 72. 21 vs 988. 66 ± 91.07, P〈0. 01 ). The content of MDA was lower and SOD level was higher in ED group significantly than in control group (P〈0. 01). As compared with control group, hepatic TNF-α levels and MPO activity at the 6th h after reperfusion were significantly decreased in ED group (P〈0. 01). Histopathological analysis revealed disruption of lobular architecture, apparent hepatocelluar degeneration accompanied by focalnecrosis, significant edema, congestion and inflammatory cell infiltration in periportal area at the 6th h after reperfusion in control group, but minimal liver damage was observed in El) group. Conclusion Edaravone could ameliorate early ischemia-reperfusion injury in small-for-size liver grafts significantly. The protective mechanisms were mediated in
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