安非他明对小鼠白细胞介素-10释放的影响及多巴胺D3受体的调控作用  

Role of dopamine receptor 3 in acute amphetamine-induced IL-10 production

作　　者：陈艳炯[1] 朱俊艳[2] 张洪波[3] 魏曙光[3] 阎春霞[3] 郑海波[3] 任会勋[1] 陈腾[3] 

机构地区：[1]西安交通大学医学院免疫学与病原生物学系,陕西西安710061 [2]西安市精神卫生中心,陕西西安710061 [3]西安交通大学医学院法医学系,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2009年第3期279-282,300,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.30572089);教育部"新世纪人才支持计划"项目(No.NCET-07-0662)~~

摘　　要：目的研究安非他明(AM)对细菌脂多糖(LPS)刺激后小鼠白细胞介素-10(interleukin-10,IL-10)释放的影响以及多巴胺D3受体在此过程中参与的调控作用。方法实验Ⅰ:采用多巴胺D3受体基因敲除小鼠(D3RKO)以及具有相似遗传背景的野生型小鼠(C57BL/6J),腹腔注射AM(5 mg/kg)10 min后再注射LPS(150μg/kg)刺激,在LPS给药后不同时间点(0、30、60、90、120、240 min)心脏穿刺抽血进行IL-10测试,观察上述不同时间点D3RKO和C57BL/6J小鼠IL-10的分泌情况。实验Ⅱ:在实验Ⅰ所确定的小鼠IL-10分泌最高时间点,观察不同剂量AM(0、2、5、10 mg/kg)对D3RKO和C57BL/6J小鼠IL-10分泌的影响。结果实验Ⅰ:AM5 mg/kg在LPS注射后可以引起D3RKO和C57BL/6J小鼠IL-10分泌增多,其中60 min达最大值,与生理盐水对照组比较差异有统计学意义(P<0.05)。实验Ⅱ:C57BL/6J小鼠以AM5 mg/kg作用后IL-10增多最为显著,D3RKO小鼠以AM2 mg/kg作用后IL-10升高最为显著,与生理盐水对照组相比差异均有统计学意义(P<0.05),且二者之间亦存在统计学差异。结论AM对小鼠免疫功能的抑制可能是通过增加IL-10分泌而起作用;小剂量AM即可引起D3RKO小鼠血中IL-10升高,提示多巴胺D3受体可能参与了AM对小鼠免疫功能抑制作用的调控。Objective To study the effects of amphetamine （AM） administration on the production of interleukin-10 （IL-10） following an intraperitoneal injection （ip） of bacterial lipopolysaccharide （LPS, 150μg/kg ） in mice and the role of dopamine D3 receptor involved in it. Methods In section Ⅰ.. dopamine D3 receptor knock-out mice （D3RKO） and wild type mice （C57BL/6J）, both exhibited a similar genetic background, received either vehicle（normal saline, NS） or AM （5 mg/kg ip） 10 min prior to LPS （150μg/kg） in vivo immune challenge, were sacrificed 0, 30, 60, 90,120, or 240 min later by anesthetized with sodium pentobarbital; in section Ⅱ： C57BL/6J and D3RKO mice received AM at different dose （0, 2, 5, 10 mg/kg） 10 min prior to either vehicle or LPS, and were sacrificed 60 min later. In anesthetized mice, blood was collected via cardiac puncture using a syringe without an anticoagulant. IL-10 of serum was measured by means of commercially available enzyme-linked immunosorbent assay. Results In section Ⅰ.. under the treatment of AM, the greatest effect was observed at 60 min after LPS challenge in both C57BL/6J and D3RKO mice. In section Ⅱ.. the administration of AM at dose of 5 mg/kg significantly increased LPS-induced IL-10 production in C57BL/6J mice, but significantly increased LPS-induced IL-10 production at dose of 2 mg/kg in Ds RKO mice, versus other doses of AM （P〈0.05）. Conclusion Our results showed that IL-10 plays a role in the immune suppression caused by AM. A smaller dose of AM increased IL-10 of D3 RKO compared with wild type, indicating that D3R mediates immune inhibition of AM.

关 键 词：安非他明 白细胞介素-10 多巴胺D3受体 细菌脂多糖 基因敲除小鼠 

分 类 号：R749.3[医药卫生—神经病学与精神病学] R575.2[医药卫生—临床医学]