Kelmer-Bracht Ana Maria, Broetto-Biazon Ana Carla, de Sá-Nakanishi Anacharis Babeto, Ishii-Iwamoto Emy Luiza, Bracht Adelar
Laboratory of Liver Metabolism, University of Maringá, 87020900 Maringá, Brazil.
Basic Clin Pharmacol Toxicol. 2006 Nov;99(5):335-9. doi: 10.1111/j.1742-7843.2006.pto_496.x.
Previous reports have attributed a stimulating action on hepatic gluconeogenesis to tumour necrosis factor alpha (TNFalpha) administered to rats at high doses (250 mug/kg). However, in adjuvant-induced arthritic rats, which present TNFalpha and other interleukins in the circulation, hepatic gluconeogenesis is diminished. The same occurs in some types of experimental cancer models as, for example, rats bearing the Walker-256 tumour. The present work represents an attempt of reproducing in rats gluconeogenesis inhibition by interleukins using low instead of high doses of both TNFalpha and interleukin 1beta (IL1beta). TNFalpha and IL1beta at doses of up to 10 mug/kg were given endovenously to rats and, after six hours, gluconeogenesis from alanine and several related parameters were evaluated in the isolated haemoglobin-free perfused rat liver. Livers from rats injected with TNFalpha and IL1beta, either alone or in combination, presented diminished gluconeogenesis. The degrees of inhibition caused by TNFalpha+IL1beta, TNFalpha and IL1beta were, respectively, 48.5, 38.8 and 30.4%. TNFalpha also diminished oxygen uptake. No action on urea and ammonia production was found. Possibly, both TNFalpha and IL1beta contribute to the decreased rates of hepatic gluconeogenesis that were found in rats with arthritis, sepsis and some kinds of cancer, but not to the decreased rates of ureagenesis.
先前的报道认为，给大鼠高剂量（250微克/千克）注射肿瘤坏死因子α（TNFα）可刺激肝脏糖异生。然而，在佐剂诱导的关节炎大鼠中，循环中存在TNFα和其他白细胞介素，但其肝脏糖异生却减少。在某些类型的实验性癌症模型中也是如此，例如，携带Walker-256肿瘤的大鼠。本研究试图在大鼠中使用低剂量而非高剂量的TNFα和白细胞介素1β（IL1β）来重现白细胞介素对糖异生的抑制作用。给大鼠静脉注射剂量高达10微克/千克的TNFα和IL1β，6小时后，在离体无血红蛋白灌注的大鼠肝脏中评估丙氨酸的糖异生及几个相关参数。单独或联合注射TNFα和IL1β的大鼠肝脏，其糖异生均减少。TNFα+IL1β、TNFα和IL1β引起的抑制程度分别为48.5%、38.8%和30.4%。TNFα还减少了氧摄取。未发现对尿素和氨生成有作用。可能TNFα和IL1β都导致了关节炎、脓毒症和某些癌症大鼠肝脏糖异生速率的降低，但对尿素生成速率降低没有影响。
