Chang C K, Llanes S, Schumer W
Department of Surgery, Finch University of Health Sciences/The Chicago Medical School at Mount Sinai Hospital Medical Center, California Avenue at 15th Street, Chicago, Illinois 60608, USA.
J Surg Res. 1997 Oct;72(2):141-5. doi: 10.1006/jsre.1997.5173.
Glucocorticoids are potent anti-inflammatory and immunosuppressive therapeutic agents. The protective effect of dexamethasone (DEX) on hepatic phosphoenolpyruvate carboxykinase (PEPCK) transcript level, hepatic NF-kB (nuclear factor-kB) activation, and serum tumor necrosis factor alpha (TNF) formation was investigated in peritoneal sepsis induced by cecal incision in rats. For the control the rats were sham-operated with laparotomies only. Each group (N = 6) was pretreated with either normal saline (NS) or DEX before surgery (NS/Sham, NS/Sepsis, DEX/Sham, and DEX/Sepsis). At 3 hr post cecal incision, DEX treatment inhibited sepsis-induced hepatic NF-kB activation by 23%, suppressed circulating TNF by 50%, reduced serum glucose by 36%, reduced hepatic glycogen depletion by 76%, and attenuated PEPCK mRNA level. These findings suggested that DEX treatment was beneficial in attenuating glucose dyshomeostasis and significantly inhibited two sepsis-induced inflammatory mediators, NF-kB and TNF, in the early phase of peritoneal sepsis. However, in the late (6 hr) septic phase, DEX treatment inhibited serum TNF by 69%, but had no effect on NF-kB activation, glycogen depletion, and PEPCK mRNA level suggesting liver function failure injury.
糖皮质激素是强效的抗炎和免疫抑制治疗药物。在大鼠盲肠切开诱导的腹腔脓毒症中，研究了地塞米松（DEX）对肝磷酸烯醇丙酮酸羧激酶（PEPCK）转录水平、肝核因子-κB（NF-κB）激活以及血清肿瘤坏死因子α（TNF）形成的保护作用。对照组大鼠仅进行假手术剖腹术。每组（N = 6）在手术前用生理盐水（NS）或DEX预处理（NS/假手术组、NS/脓毒症组、DEX/假手术组和DEX/脓毒症组）。在盲肠切开后3小时，DEX治疗使脓毒症诱导的肝NF-κB激活降低23%，使循环TNF抑制50%，使血糖降低36%，使肝糖原消耗减少76%，并使PEPCK mRNA水平降低。这些发现表明，DEX治疗有助于减轻葡萄糖稳态失衡，并在腹腔脓毒症早期显著抑制两种脓毒症诱导的炎症介质NF-κB和TNF。然而，在脓毒症晚期（6小时），DEX治疗使血清TNF抑制69%，但对NF-κB激活、糖原消耗和PEPCK mRNA水平无影响，提示肝功能衰竭损伤。
