内毒素、TNF-α及IL-6在诱导生长激素不敏感中的作用

The role of endotoxin, TNF-α and IL-6 in inducing the growth hormone insensitivity

目的 :在受体和受体后水平探讨内毒素 (LPS)、TNF α及IL 6在诱导生长激素不敏感中的作用。 方法 :采用雄性SD大鼠 ,分别静注LPS、TNF α及IL 6 ,不同时相处死大鼠。应用RT PCR法测定肝组织IGF 1、GHR和SOCS 3mRNA的表达 ;应用放射免疫法测定血清GH水平 ;应用酶联免疫吸附法测定血清TNF α和IL 6水平。 结果 :静注LPS后 ,各时间点血清GH水平与对照组无明显差异 ,血清TNF α和IL 6迅速升高 ,但TNF α很快即恢复至正常水平。肝组织IGF 1和GHRmRNA的表达分别在注射LPS后 12h和 8h下调最多。正常大鼠肝组织SOCS 3mRNA微弱表达 ,但在注射LPS后立即上调 ,在 1h时即上升了 7.84倍 ,线性回归分析显示IL 6水平与SOCS 3mRNA的表达呈高度正相关。静注TNF α后 ,肝组织SOCS 3mRNA的表达无明显变化 ,但可明显下调GHRmRNA的表达。静注IL 6后 ,肝组织GHRmRNA的表达无明显变化 ,但SOCS 3mRNA的表达却明显上调。 结论 :静注LPS可以诱导生长激素的不敏感 ,在受体水平与GHRmRNA的表达下调有关 ,在受体后水平与SOCS 3mRNA的表达上调有关。体内LPS的生物活性主要是由TNF α和IL 6介导的 ,TNF α和IL 6分别在受体和受体后水平发挥作用 ,但TNF α的作用具有滞后性。

Objectives:To investigate the role of endotoxin, TNF α and IL 6 in inducing the growth hormone insensitivity at the receptor and post receptor levels. Methods:Spague Dawley rats were injected with endotoxin, TNF α, and IL 6 respectively and were killed at different time points. The liver expressions of IGF 1, GHR and SOCS 3 mRNA were detected by RT PCR, the GH levels were measured by radioimmunoassay,and the levels of TNF α and IL 6 were detected by ELISA. Results:Serum growth hormone levels at each time points after LPS iv injection did not have significant changes compared with control rats without iv injection of LPS, TNF α and IL 6 levels were elevated rapidly after LPS injection, but TNF α levels returned to normal quickly. The most remarkable down regulations for liver IGF 1 mRNA and GHR mRNA occurred at 12h and 8h respectively after LPS infusion. The liver SOCS 3 mRNA was weakly expressed in control rats. However, it was strongly up regulated after LPS injection and had a 7.84 times increase at 1h. The linear regression analysis had shown a positive correlation between IL 6 levels and liver SOCS 3 mRNA expressions. Liver GHR mRNA expression was obviously down regulated after TNF α iv injection, but there was no effect on liver SOCS 3 mRNA expression. IL 6 up regulated the liver SOCS 3 mRNA expression, but it could not affect the liver GHR mRNA expression. Conclusions:The growth hormone insensitivity could be induced by LPS injection, which was associated with down regulated GHR mRNA expression at receptor level and up regulated SOCS 3 mRNA expression at post receptor level. The biological activities of LPS are mediated by TNF α and IL 6 indirectly.And TNF α and IL 6 exert their effects on the receptor and post receptor levels respectively, but the effect of TNF α is of hysteresis.