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浅蓝霉素预处理对小鼠原位脂肪肝移植的影响 被引量:1

Fatty acid synthase inhibition proves protective in a fatty liver transplantation model
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摘要 目的 探讨供体浅蓝霉素预处理对原位小鼠脂肪肝移植保护作用及机制。方法 建立小鼠原位肝移植模型。随机分为正常小鼠组 (n =8)、肥胖小鼠组 (n =8)、非脂肪肝移植组 (n =12 )、脂肪肝移植组 (n =12 )、浅蓝霉素预处理 2d脂肪肝移植组 (n =12 )与预处理 4d脂肪肝移植组 (n =12 )。检测肝功能 ,肝脏组织苏木素 伊红 (HE)染色 ,油红O染色脂肪定量 ,ATP含量及解偶联蛋白 2 (UCP 2 )水平测定。结果 浅蓝霉素预处理的两实验组 2h存活率 (67%、83 % )明显高于未经浅蓝霉素预处理脂肪肝移植组 (2 5 % ) ,血清ALT水平、脂肪容量、线粒体UCP 2水平明显低于后者 ,分别为 (2 3 16± 662 )IU/L、(12 3 0± 3 2 1)IU /L比 (83 2 0± 465 5 )IU/L ;(5 0± 8) %、(3 0±6) %比 (70± 8) % ;(14 .2 1± 1.82 )、(8.74± 0 .97)比 (18.80± 2 .3 3 )。光镜下肝细胞损伤程度亦低于后者 ,而ATP浓度明显高于后者 ,分别为 (0 .2 5± 0 .0 1)、(0 .5 7± 0 .0 1)与 (0 .13± 0 .0 1) ,P均 <0 .0 5。结论 浅蓝霉素预处理对小鼠脂肪肝移植有明显保护作用。 Objective To study the influence of cerulenin pretreatment on mouse orthotopic liver transplantation(OLTx).Methods Using the non arterialized mouse OLTx model,size matched lean and ob/ob(steatosis) donormice were transplanted into lean recipients.cerulenin was administered for either two or four days intraperitoneally(i.p.) at 60 μg·kg -1 ·d -1 prior to donation.Endpoints include survival,serum ALT and AST,hepatocyte injury by H&E,intrahepatocyte lipid content via Oil Red O staining,hepatocyte ATP and UCP 2 levels.Results When ob/ob mice were pretreated with cerulenin for 2 or 4 days,survival of lean mice receiving these livers was significantly higher respectively at 2hrs (67% or 83% vs 25%).The survival data was paralleled by attenuation of markers of hepatocyte injury,serum ALT,and a decrease in steatosis and UCP 2,and a increase in ATP with cerulenin pretreatment [respectively,(2?316±662) IU/L or (1?230±321) IU/L vs (8?320±4655) IU/L;(50±8)% or (30±6)% vs.(70±8)%;(14.21±1.82) or (8.74±0.97) vs (18.80±2.33)];[(0.25±0.01) or (0.57± 0.01) vs (0.13±0.01)], P <0.05.Conclusion Attenuation of donor liver intrahepatocyte lipid content by administration of cerulenin is protective and improves survival following OLTx.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2004年第6期681-683,i003,i004,共5页 Chinese Journal of Experimental Surgery
关键词 浅蓝霉素 预处理 小鼠 脂肪肝 肝移植 解偶联蛋白-2 Liver transplantation Steatosis Cerulenin UCP-2
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  • 2Kimmich GA,Randles J,Brand JS.Assay of picomole amounts of ATP,ADP, and AMP using the luciferase enzyme system[].Analytical Biochemistry.1975
  • 3Qian S,Fu F,Li Y,et al.Impact of donor MHC class I or class II antigen deficiency on first and second-set rejection of mouse heart or liver allografts[].Immunology.1996
  • 4Clavien PA,Selzner M.Hepatic steatosis and transplantation[].Liver Transplantation.2002

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