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目的:通过注射内毒素(LPS)建立的大鼠脓毒症模型,观察胰岛素不同时机给药对血清和肝细胞因子表达的影响。方法:将81只大鼠分为九组,即A组腹腔注射等渗盐水;B组腹腔注射LPS;C、D、E、F、G、H、I组分别在腹腔注射LPS前30 min和注射后0、1、3、6、12、24 h给予胰岛素治疗。观察各组大鼠LPS注射后24和48h血清白细胞介素-1β(IL-1β)、IL-6、肿瘤坏死因子α(TNF-α)和IL-10的变化,以及LPS注射48 h后肝组织IL-1β、IL-6、TNF-α和IL-10的变化。结果:注射LPS后24和48 h,大鼠血IL-1β、IL-6、TNF-α和IL-10均显著增加。LPS注射48 h后,肝组织中IL-1β、TNF-α、IL-6和IL-10蛋白水平也明显增加。在注射LPS前30 min或注射后6 h内给予胰岛素,能明显降低注射后24和48 h血清中的IL-1β、TNF-α和IL-6水平(P<0.05);而IL-10水平则仅在注射LPS前或注射同时给予胰岛素,才较LPS组明显增加(P<0.05)。在LPS注射前30 min或注射后6 h内给予胰岛素,注射后48 h肝内的IL-1β和TNF-α水平较LPS组明显降低(P<0.05);而肝的IL-6水平仅在LPS注射前30min或与同时给予胰岛素时,才较LPS组明显降低(P<0.05)。结论:胰岛素对脓毒症大鼠有抑制炎性细胞因子,增加抗炎介质释放等保护作用。在注射LPS 6 h内给予胰岛素可发挥良好的抗炎保护作用,而在注射LPS 6 h后给予胰岛素治疗其抗炎保护作用明显减弱。
OBJECTIVE: To observe the effects of different doses of insulin on the expression of serum and hepatocyte factors in rat sepsis model by injecting endotoxin (LPS). Methods: 81 rats were divided into nine groups, namely, group A, intraperitoneal injection of isotonic saline; group B, intraperitoneal injection of LPS; group C, D, E, F, G, H, Insulin treatment was given at 0,1,3,6,12,24 h after injection. The changes of serum IL-1β, IL-6, TNF-α and IL-10 at 24 and 48 hours after LPS injection in each group were observed, Tissue IL-1β, IL-6, TNF-α and IL-10 changes. Results: The levels of IL-1β, IL-6, TNF-α and IL-10 were significantly increased at 24 h and 48 h after LPS injection. After 48 h of LPS injection, the levels of IL-1β, TNF-α, IL-6 and IL-10 in liver tissue also increased significantly. The level of IL-1β, TNF-α and IL-6 in serum at 24 h and 48 h after injection of insulin was significantly decreased at 30 min before injection of LPS or within 6 h after injection of LPS (P <0.05) Then only injected with LPS or injected with insulin at the same time, compared with LPS group was significantly increased (P <0.05). The level of IL-1β and TNF-α in the liver at 48 h after injection of insulin was significantly lower than that of the LPS group (P <0.05) at 30 min before LPS injection or within 6 h after injection. The level of IL-6 in the liver was only LPS group was significantly lower than that of LPS group (P <0.05) 30 minutes before or 30 minutes before LPS injection of insulin. Conclusion: Insulin can inhibit inflammatory cytokines and increase the release of anti-inflammatory mediators in septic rats. Insulin administration within 6 h after injection of LPS exerted a good anti-inflammatory protective effect, whereas the anti-inflammatory protective effect of insulin administered 6 h after LPS injection was significantly attenuated.