生长激素对脓毒症大鼠保护作用的机制研究

Study on protecting mechanism of growth hormone on the rats with sepsis

目的研究重组人生长激素对脓毒症大鼠的免疫调节作用。方法将24只清洁级Wistar大鼠,随机分为对照组以及大、小剂量预处理组,分别给予生理盐水以及大剂量[3 U/(kg.d)]、小剂量[1 U/(kg.d)]重组人生长激素。治疗5 d后,尾静脉注射大肠杆菌内毒素标准品(10 mg/kg),制成脓毒症模型,检测造模前后大鼠血清中TNF-α和IL-10的水平。结果各组注射内毒素前血清TNF-α、IL-10水平差异无显著性(P>0.05),对照组内毒素注射后,血清TNF-α和IL-10均呈升高趋势,造模后4 h达到最高值(P<0.001)。大、小剂量组TNF-α在内毒素注射后各时点均显著低于对照组水平(P<0.005);造模后2 h,大剂量组IL-10明显高于对照组(P<0.001);造模后4 h,大、小剂量组IL-10均明显低于对照组水平(P<0.005)。结论生长激素可以抑制脓毒症早期机体过度产生TNF-α,并对IL-10的产生有双相调节作用(早期抑制炎症反应,后期削弱过度抑制),从而及时适度的调节脓毒症机体的细胞因子网络,纠正脓毒症导致的免疫系统功能紊乱。

Objective To investigate the immunoregulatory effect of recombinant human growth hormone （rhGH） on the rats with sepsis, Methods Male Wistar rats were randomized into 3 groups： high, low dose rhGH group [ 3 and 1 U/（ kg·d）] and control group（ normal saline solution）, rhGH or saline solution were administered subcutaneously for 5 days. Then the rats were challenged with E coli lipopolysaccharide （10 mg/ kg） via tail vein 12 hours after the last subcutaneous administration of rhGH or saline solution, Finally, serum TNF-α and IL-10 level before and after lipopolysaccharide challenge were measured, Results There was no significant difference in serum TNF-α or IL-10 among the three groups before lipopolysaccharide challenge（P 〉0.05）. The serum TNF-α and IL-10 levels in the control group tended to be higher compared with the prechallenge levels, and risen significantly at 4 hours after lipopolysaccharide challenge （P 〈 0. 001 ）, However, TNF-α levels in the high and low dose groups were significantly lower than that in the control group at 1 to 4 hours after lipopolysaccharide challenge （ P 〈 0. 005 ）. IL-10 level at 2 hour was significantly higher in the high dose group as compared with the control group （P〈0.001）, but IL-10 level in the high and low dose groups was significantly lower than that in the control group at 4 hour after lipopolysaccharide challenge （P 〈 0. 005）. Conclusion GH can inhibit excessive TNF-α release in the early stage of sepsis and exert biphasic effect on IL-10 expression（GH inhibits inflammatory response in the early stage and avoids excessive inhibition）. GH can modulate cytokine network and correct the immune dysfunction in the rat with sepsis.