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。将雄性SD大鼠经脑室和颈静脉插管。治疗在术后6天进行。采用恒定输注法测定葡萄糖产量和蛋白质周转率。用库仑分析法测定脑组织中的吗啡水平。脑室注射肿瘤坏死因子α(600 Ng)后，葡萄糖生成量和全身蛋白质分解率均增加，肌肉蛋白质合成率降低。这种代谢变化与血清皮质酮和儿茶酚胺水平的增加有关。与对照组相比，全身应用肿瘤坏死因子对代谢和激素的影响无明显差异，提示存在一条通过中枢神经系统促进细胞因子介导的代谢改变的重要途径。预防性给予芬太尼(50mU/g/kg)可抑制脑内注射肿瘤坏死因子所致的代谢改变。此外，全身应用芬太尼可抑制脑室注射肿瘤坏死因子引起的血清应激激素水平的升高。提示阿片受体参与了中枢神经系统细胞因子介导的代谢变化。脑室注射肿瘤坏死因子后，脑内吗啡水平升高，全身注射肿瘤坏死因子后，脑组织吗啡水平无明显变化。此外，预防性应用芬太尼可抑制脑室注射肿瘤坏死因子引起的脑内吗啡水平升高。

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.