[Changes in adrenal cortex function and protective effect of dexamethasone in septic rats during early phases].
摘要
OBJECTIVE: To affirm the presence of relative adrenal insufficiency (RAI) in the early phases of sepsis and its probable mechanisms, and to study the optimal time for glucocorticoid replacement therapy. METHODS: A total of 260 healthy male Wistar rats were randomized into five groups (each group n=52), including normal control group, sham operation group, cecal ligation and puncture (CLP) group, dexamethasone prevention group (with 10 mg/kg dexamethasone injection into the abdominal cavity before CLP) and dexamethasone treatment group (with 10 mg/kg dexamethasone injection into the abdominal cavity 7 hours after CLP). Each group was subdivided into five subgroups according to five time points: 2, 4, 6, 8 and 12 hours. Adrenocorticotrophic hormone (ACTH) test was conducted at 8 hours and 12 hours, and before and after 30 minutes of ACTH administration, the cortisol content in serum was determined with radioimmunoassay (RIA) and the expressions of Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-alpha) mRNA in adrenal glands were detected with semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Ultrastructure of adrenal cortex was observed with transmission electron microscope. The survival rats was recorded in all groups. RESULTS: (1) The levels of cortisol in CLP group, dexamethasone prevention group and dexamethasone treatment group were respectively higher than those of normal control and sham operation groups (all P<0.05). But there was no marked change in the levels of cortisol between pre-and post-ACTH in rats with sepsis in the early phases. (2)The expressions of TLR4, TNF-alpha mRNA in adrenal both were significantly increased in CLP group, and they were higher than those in sham operation group (P<0.05 or P<0.01). The expressions of TLR4, TNF-alpha mRNA in dexamethasone prevention group and treatment group were significantly lower than those in CLP group, and those in the dexamethasone prevention group were lower than thos