Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Independencia 1027, Casilla 70000, Santiago 7, Chile.
Mol Cell Endocrinol. 2010 Jul 29;323(2):292-7. doi: 10.1016/j.mce.2010.03.014. Epub 2010 Mar 18.
We studied the role of Kupffer cell functioning in T3 liver preconditioning against ischemia-reperfusion (IR) injury using the macrophage inactivator gadolinium chloride (GdCl3) previous to T3 treatment. Male Sprague-Dawley rats given a single i.p. dose of 0.1 mg T3/kg were subjected to 1 h ischemia followed by 20 h reperfusion, in groups of animals pretreated with 10 mg GdCl3/kg i.v. 72 h before T(3) or with the respective vehicles. IR resulted in significant enhancement of serum aspartate aminotransferase (3.3-fold increase) and tumor necrosis factor-alpha (93% increase) levels, development of liver damage, and diminished nuclear factor-kappaB DNA binding over control values. These changes, which were suppressed by the T3 administration prior to IR, persisted in animals given GdCl3 before T3 treatment, under conditions of complete elimination of ED2+ Kupffer cells achieved in a time window of 72 h. It is concluded that Kupffer cell functioning is essential for T3 liver preconditioning, assessed in a warm IR injury model by hepatic macrophage inactivation.
我们使用巨噬细胞失活剂氯化钆（GdCl3）在给予三碘甲状腺原氨酸（T3）治疗之前研究枯否细胞功能在 T3 肝预处理对缺血再灌注（IR）损伤中的作用。雄性 Sprague-Dawley 大鼠给予单次腹腔注射 0.1 mg/kg T3/kg，然后进行 1 小时缺血，然后再进行 20 小时再灌注，在动物组中，用 10 mg/kg GdCl3 静脉内预处理 72 小时。IR 导致血清天冬氨酸转氨酶（增加 3.3 倍）和肿瘤坏死因子-α（增加 93%）水平显著升高，肝损伤发展，并降低核因子-κB DNA 结合活性相对于对照值。这些变化在给予 GdCl3 之前给予 T3 治疗的动物中持续存在，在这种情况下，72 小时的时间窗口内实现了 ED2+枯否细胞的完全消除。结论是，在通过肝巨噬细胞失活评估的温热 IR 损伤模型中，枯否细胞功能对于 T3 肝预处理是必需的。
