Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression
Inactivation of Kupffer cells by gadolinium administration prevents lipopolysaccharide-induced decrease in liver insulin-like growth factor-I and IGF-binding protein-3 gene expression
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DOI：
10.1677/joe.1.06585
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发表时间：
2006-03-01
影响因子：
4
通讯作者：
López-Calderón, A
中科院分区：
文献类型：
--
作者：
Granado, M;Martin, AI;López-Calderón, A
革兰氏阴性细菌感染或用细菌脂多糖（LPS）处理动物诱导具有蛋白水解、肝损伤和胰岛素样生长因子-I（IGF-I）系统抑制的分解代谢状态。本工作的目的是阐明枯否细胞在LPS诱导的IGF-1/IGF-结合蛋白-3（IGFBP-3）系统抑制中的作用。将成年雄性Wistar大鼠用枯否细胞抑制剂氯化钆（10 mg/kg，静脉内，LPS暴露前24小时）或盐水媒介物。大鼠接受两次1 mg/kg LPS腹腔注射（第二天17：30和08：30 h），并在第二次注射后4 h处死。LPS给药诱导体重和血清IGF-I和IGFBP-3浓度显著降低（P < 0.01），肝脏中IGF-I和IGFBP-3的基因表达也显著降低。LPS组大鼠血清ACTH、皮质酮（P < 0.05）、肿瘤坏死因子-α（TNF-α）和芸香碱（P < 0.01）水平明显升高。用氯化钆对动物进行预处理阻断了LPS对体重、对IGF-1、IGFBP-3和亚硝酸盐的血清浓度以及对肝脏中生长激素受体（GHR）、IGF-I和IGFBP-3基因表达的抑制作用。相反，氯化钆给药并没有改变LPS对ACTH、皮质酮和TNF-α血清浓度的刺激作用。这些结果表明，枯否细胞是LPS抑制肝脏中GHR、IGF-I和IGFBP-3基因表达的重要介质，导致血清中IGF-I和IGF-BP-3浓度降低。
Gram-negative bacterial infection or treatment of animals with bacterial lipopolysaccharide (LPS) induces a catabolic state with proteolysis, liver injury and an inhibition of the insulin-like growth factor-I (IGF-I) system. The purpose of this work was to elucidate the role of Kupffer cells in LPS-induced inhibition of the lGF-I/IGF-binding protein-3 (IGFBP-3) system. Adult male Wistar rats were either pretreated with the Kupffer cell inhibitor gadolinium chloride (10 mg/kg, i.v., 24 h prior to LPS exposure) or saline vehicle. Rats received two i.p. injections of 1 mg/kg LPS (at 17:30 and 08:30 h the following day) and were killed 4 h after the second injection. LPS administration induced a significant decrease in body weight and in serum concentrations of IGF-I and IGFBP-3 (P < 0.01), as well as in their gene expression in the liver. LPS-injected rats had increased seruni concentrations of ACTH, corticosterone (P < 0.05), turnout necrosis factor-a (TNF-alpha) and rutrites (P < 0.01). pretreatment of the animals with gadolinium chloride blocked the inhibitory, effect of LPS on body weight, and on serum concentrations of ICF-I, IGFBP-3 and nitrites, as well as growth hormone receptor (GHR), IGF-I and IGFBP-3 gene expression in the liver. In contrast, gadolinium chloride administration did not modify the stimulatory effect of LPS on serurn concentrations of ACTH, corticosterone and TNF-alpha. These results suggest that Kupffer cells are important mediators in the inhibitor effect of LPS on GHR, IGF-I and IGFBP-3 gene expression in the liver, leading to a decrease in serurri concentrations of IGF-I and IGF.BP-3.