不同剂量氢化可的松对早期脓毒性休克大鼠炎症介质分泌的影响

Effects of hydrocortisone on inflammation mediator secretion in early septic shock rats

目的研究不同剂量氢化可的松（HC）对早期脓毒性休克大鼠炎症介质分泌的影响。方法建立早期脓毒性休克大鼠模型，观察不同剂量HC对早期脓毒性休克的作用。40只模型大鼠随机分为5组：对照组、休克组、氢化可的松大剂量组（HD）、中剂量组（MD）、小剂量组（LD）．监测血液炎症介质水平及皮质醇、ACTH分泌水平。结果休克组TNF—α较对照组明显升高[（0．22±0．05）Pg／ml、vs（0．10±0．08）pg／ml]；应用HC后，不同剂量组与休克组比较，差异无显著性（P〉0．05）。休克组IL．1B较对照组明显升高[（0．11±0．07）Pg／ml vs（0．04±0．01）pg／ml]，应用HC后，三组均较休克组有所下降，LD组与休克组相比，差异有显著性（P〈0．05）。休克组血浆NO、一氧化氮合酶（NOS）均较对照组明显升高[分别为（9．804±1．616）μmol／L vs（4．934±1．405）μmol／L；（31．304±1．572）U／ml VS（24．866±0．925）U／m1]。应用HC后。LD组血浆NO、NOS较休克组明显降低（P〈0．05）；H13、MD组仍高于休克组，但差异无显著性。应用HC后，三组皮质醇水平均明显升高；三组的ACTH水平均较休克组明显降低（P〈0．05），但三组间差异无显著性。结论脓毒性休克早期，炎症介质TNF-α、IL-1β、NO、NOS明显升高，可直接作用于肾上腺刺激皮质醇分泌，对下丘脑．垂体．肾上腺皮质轴有相应调节作用。通过不同剂量HC给药观察，过量的皮质醇不能抑制炎症反应。小剂量HC作用后IL-1β、NO均接近正常水平，对循环功能稳定作用较大、中剂量HC为佳。

Objective To assess the effects of different doses of hydrocortisone （HC） on early septic shock rats and observe the change of inflammation mediators. Methods The early septic shock model was established by interval injection of E. coli O111：B4 in pathogen-free Wistar male rats. Wistar rats were randomly divided into five groups： Control group, septic shock group, high dose of HC group （ HD group）, middle dose of HC group（MD group）, and low dose of HC group （LD group）. The levels of cortisol and ACTH and plasma inflammation mediators were determined. Results TNF-α level of septic shock group increased significantly as compared with control group [ （0.11 ± 0.07） pg/ml vs. （0.04 ± 0.01 ） pg/ml]. But all the three HC-treated groups showed no significant difference in TNF-α level as compare with septic shock group. IL-1β level of septic shock group increased significantly as compared with control group [（0.11± 0.07） pg/ml vs. （0.04 ± 0.01 ） pg/ml]. After HC administration, as compared with that of septic shock group, all the three HC-treated groups showed a decrease but only LD group decreased significantly [ （0.05±0.03） pg/ml, P 〈 0.05 ]. Plasma NO [（9.804 ± 1.616） μmol/L] and NOS [（31.304 ± 1.572） U/ml] of septic shock group increased significantly compared with those of control group [（4.934 ± 1.405） μmol/L and （24.866 ± 0.925） U/ml for NO and NOS repectively）]. Compared with septic shock group, those of LD group [ （5.789 ±1. 014 ） μmol/ L, （28. 314 ± 3. 326） U/ml for NO and NOS repectively] decreased significantly, and there was no difference in contrast to that of control group. Although NO and NOS levels of HD and MD group were higher than septic shock group, but there was no significant difference. Cortisol level of septic shock group was significantly higher than that of control group （P 〈 0.05）;but ACTH level had no significant difference in contrast to that of control group. After HC administration, cortisol levels in all 3 groups increased significantly, which was dosedependent. The cortisol increase of HD and MD group were greater than that of LD group;ACTH levels in 3 groups were all lower than that of septic shock group （ P 〈 0.05）, but no significant difference was shown between any two of the 3 groups. Conclusion TNF-α, IL-1β,NO,NOS in early septic shock increased significantly, suggesting their involvement in regulating hypothalamic-pituitary-adrenal axis that affects adrenal-stimulating cortisol secretion. After different doses of HC, the resuhs indicate that excess cortisol cannot inhibit the production of inflammation mediators. After low dose of hydrocortisone administration, IL-1β and NO level almost return to normal, which contributes to the increasing stability of circulating function.