Destruction of Kupffer cells increases survival and reduces graft injury after transplantation of fatty livers from ethanol-treated rats.

Destruction of Kupffer cells increases survival and reduces graft injury after transplantation of fatty livers from ethanol-treated rats.
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乙醇处理的大鼠脂肪肝移植后,库普弗细胞的破坏可增加存活率并减少移植物损伤。

DOI:
10.1002/lt.500020509
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发表时间:
1996
期刊:
Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.
影响因子:
--
通讯作者:
Thurman,RG
Thurman,RG
中科院分区:
--
文献类型:
--
作者:
Zhong,Z;Connor,H;Mason,RP;Qu,W;Stachlewitz,RF;Gao,W;Lemasters,JJ;Thurman,RG

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本研究探讨了枯否细胞在急性乙醇处理的大鼠移植脂肪肝存活和移植物损伤中的作用。供体大鼠在移植前20小时给予乙醇(5 g/kg,经口),肝移植物在植入前在威斯康星州大学冷藏溶液中保存24 - 42小时。植入后3小时从下腔静脉采集血样。在此期间,对照组大鼠的血清天冬氨酸转氨酶水平从122 U/L逐渐升高至597 U/L,而乙醇处理组的值升高至2,278 U/L。氯化钆(20 mg/kg,在移植前24小时静脉注射给受者)是一种选择性枯否细胞灭活剂,可显著降低天冬氨酸转氨酶水平的升高。对照组大鼠移植后存活率为88%,而乙醇组大鼠移植后存活率仅为33%。氯化钆改善生存率接近对照值。乙醇几乎使白色血细胞粘附力增加一倍,这种作用也在很大程度上被氯化钆阻断。此外,乙醇处理使胆汁中检测到的α-(4-吡啶基1-氧化物)-N-叔丁基硝酮自由基加合物增加两倍。这种效应也被氯化钆逆转。总之,这些数据表明,乙醇处理的大鼠脂肪肝的存活率更差,移植物损伤更大。枯否细胞的灭活最大限度地减少了移植物损伤,最有可能是通过改善肝脏微循环和减少脂质过氧化作用。版权所有© 1996美国肝病研究协会。
This study investigated the role of Kupffer cells on survival and graft injury in transplanted fatty livers from rats treated acutely with ethanol. Donor rats were given ethanol (5 g/kg, by mouth) 20 hours before explantation, and liver grafts were preserved in University of Wisconsin cold storage solution for 24 to 42 hours prior to implantation. Blood samples were taken from the inferior vena cava for 3 hours after implantation. During this time, serum aspartate transaminase levels increased gradually from 122 U/L to 597 U/L in control rats, while ethanol treatment elevated values to 2,278 U/L. Gadolinium chloride (20 mg/kg, given intravenously to recipients 24 hours before explantation), a selective inactivator of Kupffer cells, minimized the increase in aspartate transaminase levels significantly. After implantation of grafts cold-stored for 42 hours, survival rates were 88% in control rats but only 33% in ethanoltreated rats. Gadolinium chloride improved survival nearly to control values. Ethanol nearly doubled white blood cell adhesion, an effect also largely blocked by gadolinium chloride. Further, α-(4-pyridyl 1-oxid)-N-tert-butylnitrone radical adducts detected in the bile were increased twofold by ethanol treatment. This effect was also reversed by gadolinium chloride. Taken together, these data indicate that survival is poorer and graft injury is greater in fatty livers from ethanoltreated rats. Inactivation of Kupffer cells minimized graft damage, most likely by improving hepatic microcirculation and diminishing lipid peroxidation. Copyright© 1996 by the American Association for the Study of Liver Diseases.