The role of opioid agonist and cytokine in metabolic changes mediated by central nervous system

这一系列实验的目的是确定阿片受体是否参与细胞因子介导的代谢变化。雄性SD大鼠经脑室和颈静脉插管。术后第6天开始治疗。葡萄糖的产生和蛋白质的转换通过恒定输注1-^<13> c -亮氨酸和6-^3 h -葡萄糖的方法来测量。用库仑法测定脑内吗啡水平。脑室内注射TNFalpha （600ng）可增加葡萄糖产量和全身蛋白质分解率，降低肌肉蛋白质合成率。这种代谢变化与血清皮质酮和儿茶酚胺水平的增加有关。相反，与对照组相比，全身给药TNF的代谢和激素变化没有差异，这表明存在通过中枢神经系统促进细胞因子介导的代谢变化的重要途径。预防性给予枸橼酸芬太尼（50mu/g/kg）可抑制脑内注射TNF诱导的代谢改变。此外，全身给药芬太尼抑制了ICV注射TNF诱导的血清应激激素水平的升高。提示阿片受体通过中枢神经系统参与细胞因子介导的代谢改变。脑内注射TNF后，脑内吗啡水平升高，全身注射TNF后，脑内吗啡水平未见升高。此外，芬太尼的预防性管理可以防止ICV THF诱导的脑吗啡水平的增加。我们认为细胞因子引起的代谢变化部分通过中枢神经系统介导，阿片受体参与了这一途径。

The objective of theses series of experiment was to determine whether opioid receptor was involved in cytokine mediated metabolic change. Male SD rats were catheterized into the cerebroventricular and jugular vein. The treatment was performed 6 days after the surgery. Glucose production and protein turnover were measured by a constant infusion method of 1-^<13> C-leucine and 6-^3 H-glucose. Morphine levels in the brain were determined, using coulometry analysis. Intra-cerebroventicular (ICV) injection of TNFalpha (600ng) caused an increase in both glucose production and whole body protein breakdown rate, and a decrease in muscle protein synthesis rate. This metabolic change was associated with an increase in serum corticosterone and catecholamine levels. In the contrary, these were no differences in metabolic and hormonal changes with systemic administration of TNF compared to the control group, suggesting that there is a significant pathway to facilitate metabolic changes mediated by cytokine via central nervous system.Metabolic alteration induced by intra-cerebral injection of TNF was inhibited by prophylactic administration of fentanyl citrate (50mu/g/kg). Furthermore, systemic administration of fentanyl inhibited an increase in the serum stress hormone levels induced by ICV injection of TNF.These results suggested that opioid receptor was involved in cytokine mediated metabolic alteration via central nervous system.Morphine levels in the brain were increased with ICV injection of TNF,but no increase was found with systemic injection of TNF.Furthermore, prophylactic administration of fentany prevented an increase in the brain morphine levels induced by ICV THF.We concluded that metabolic change induced by cytokine was partially mediated via central nervous system and opioid receptor was involved in this pathway.