蓝斑核Orexin-A对肥胖抵抗大鼠自发活动的影响及机制研究  

Effects of the Orexin-A in Locus Coeruleus in Spontaneous Activities of Obesity-resistant Rats

作　　者：秦辉[1,2] 孙姝[1] 逄明杰[3] 郭菲菲[1] 孙向荣[1] 公衍玲[4] 徐珞[1] 

机构地区：[1]青岛大学医学院病理生理教研室,山东青岛266021 [2]青州云门山卫生院,山东潍坊262500 [3]青岛市立医院,山东青岛266000 [4]青岛科技大学,山东青岛266042

出　　处：《现代生物医学进展》2016年第6期1018-1022,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81470815;31071014;81100260;81270460;81300281);山东省优秀中青年科学家科研奖励基金项目(BS2014YY009);青岛市科技局项目(13-1-4-170-jch;14-2-3-3-nsh)

摘　　要：目的:探讨蓝斑核(LC)orexin-A对肥胖抵抗(OR)大鼠自发活动的影响及机制并进一步探究LC的orexin调控是否与肥胖抵抗相关。方法:雄性SD大鼠和选择性培育的OR大鼠,一侧蓝斑核置管,缓慢均匀注射0.5μL药物(orexin-A或人工合成脑脊液),用大鼠自发活动检测装置SPA箱红外线活动传感器测定测大鼠自发活动(SPA),间接测热法测定其能量消耗,定量磁共振身体组成分析器检测大鼠脂体重和瘦体重。大鼠肥胖程度用体脂百分比表示。结果:与SD大鼠相比,OR大鼠的总体重,脂体重和去脂体重显著降低(P<0.05)。OR大鼠肥胖程度明显小于SD大鼠(P<0.05)。OR大鼠在3月龄是主要表现为水平活动,6月龄时垂直活动增加,故OR大鼠随年龄增长活动量显著增多(P<0.05)。OR大鼠注射orexin A增加SPA的作用比SD大鼠更强,其主要原因是OR大鼠水平活动时间明显高于垂直活动时间。与SD大鼠相比,OR大鼠SPA水平高、体重轻,日间能量消耗和SD大鼠无明显差异,夜间活动消耗更多能量。在OR大鼠的LC注射orexin-A后,两组高剂量orexin-A可显著增加SPA(P<0.05),并呈现剂量依赖性。对于SD大鼠,只有最高剂量的OXA才能引起SPA显著高于对照组(P<0.05)。最高剂量的两组orexin-A注射后,OR大鼠SPA改变比SD大鼠更显著(250 pmol:P<0.05;500 pmol:P<0.05)。结论:蓝斑核(LC)orexin-A对肥胖大鼠自发活动有重要影响,其orexin调控与肥胖抵抗相关。Objective：To investigate the role of the locus coeruleus（LC） in enhanced orexin-A induced spontaneous activities of obesity-resistant rats and its mechanism and further explore whether LC associated with obesity resistance.Methods：Male Sprague-Dawley and selectively bred OR rats were used.A 26-gauge stainless steel cannula was directed towards the LC of rats.Orexin-A and the vehicle was injected through the cannula tract.And then,measured SPA,Indirect Calorimetry,total fat and fat-free mass.Adiposity was expressed by percent body fat.Results：Compared with SD rats,the OR rats had significantly lower body weight,fat and fat-free mass（P0.05）.OR rats showed significantly less adiposity（P0.05） than SD rats.OR rats spent more time ambulating at 3month of age and spent more time vertical at 6 months of age.This resulted in OR rats spending significantly more time moving as increase of age（P0.05）.After the injection of orexin-A,SPA of OR rats was higher than SD rats cause ambulating of OR rats significantly more than vertical activities.The OR rats have higher SPA,lower body weight,and yet the same daily energy expenditure as Sprague-Dawley rats which suggests that OR rats expend more energy on activities during the dark period.In OR rats,the two highest doses of orexin-A increased SPA significantly（P 0.05 for both doses） and this was dose dependent.In contrast,in Sprague-Dawley rats only the highest dose of orexin-A significantly increased SPA relative to vehicle（P 0.05）.The two highest doses of orexin-A significantly increased SPA more robustly in OR rats relative to SD rats（250 pmol：P0.05;500 pmol：P0.05）.Conclusions：Orexin-A infused into the LC stimulated SPA and related to obesity resistance.

关 键 词：OREXIN-A 大鼠自发活动检测 蓝斑核 肥胖抵抗性大鼠 能量消耗 

分 类 号：R338.2[医药卫生—人体生理学] R33[医药卫生—基础医学]