硫前列酮影响小鼠代谢的NMR研究

NMR-Based Metabonomic Analysis for Sulprostone-Induced Mice

前列腺素E2(PGE2)作为一种体内广泛分布的活性物质,通过与其特异性受体EP1,EP2,EP3和EP4结合实现信号跨膜转导,参与许多重要的生理病理过程.硫前列酮作为PGE2的类似物,通过激活EP1和EP3受体发挥其生理作用,但相关的代谢基础还不甚清楚.该研究运用基于核磁共振(NMR)技术的代谢组学方法研究了EP1和EP3受体激活剂硫前列酮对小鼠血清和肝脏代谢组的影响.结果表明,中高剂量硫前列酮处理32天会导致小鼠肝脏代谢组中的烟酰胺腺嘌呤二核苷酸磷酸、烟酰胺腺嘌呤二核苷酸、二磷酸尿苷、磷酸腺苷和胆汁酸的明显增加,同时肝糖原、葡萄糖、苯丙氨酸、酪氨酸、尿苷、肌苷、烟碱酸和氧化型谷胱甘肽明显减少.恢复3周后,高剂量硫前列酮处理小鼠会导致肝脏代谢组中的胆碱水平比对照组高.这些结果表明EP1和EP3受体激活剂硫前列酮会对小鼠肝脏的糖、核酸和氨基酸等代谢产生影响.同时,未发现硫前列酮对血清代谢组产生明显影响,这可能与血液循环系统维持机体内环境相对稳定有关.以上研究结果为认识PGE2-EP1/3信号通路在代谢中的作用提供了基础数据.

Prostaglandin E2 （PGE2） is a widely distributed substance in body, and in- volved in many physiological and pathological processes. It regulates signal transduction pathways through binding to EP1, EP2, EP3 and EP4 receptors. PGE2 is also. Sulpr- ostone is an analogue of PGE2, playing its physiological functions through activation of EP1 and EP3. The metabolic foundation of PGE2 is still poorly understood. This work studied the metabonome of serum and liver in sulprostone-induced mice using nuclear magnetic resonance （NMR）-based analysis. The results showed that following 32 days of sulprostone treatment （i. e. , 0. 1 mg/kg, medium dose; 1 mg/kg, high dose）, the animals showed significantly increased NADP＋ , NAD＋ , UDP, AMP and bile acids lev- els, and significantly reduced levels of glycogen, glucose, phenylalanine, tyrosine, uri- dine, inosine, nicotinic acid and GSSG in the liver. After three-weeks of recovery, cho- line elevation persisted in the high dose group. These results indicated that sulprostone caused metabolic disturbance of glucose, nucleic acid and amino acids in the liver. No sulprostone induced changes were observed in the serum data, probably due to hemeostasis. The results obtained provided more insights into the PGE2-EP1/3-signa-ling pathways in mouse, especially in the metabolic aspects.