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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 effect and mechanism of orexin-A of locus coeruleus (LC) on spontaneous activity in obese rats with obesity, and to further explore whether orexin regulation of LC is related to obesity resistance. METHODS: Male Sprague-Dawley rats and selective OR rats were stained with locus coeruleus and 0.5 μL of drugs (orexin-A or synthetic cerebrospinal fluid) were injected slowly and evenly. The spontaneous activity of rat spontaneous activity detection device The sensor was used to measure the spontaneous activity of rats (SPA), the indirect calorimetry was used to measure the energy expenditure, and the quantitative body composition analyzer was used to detect the body weight and body weight of rats. The degree of obesity in rats is expressed as body fat percentage. Results: Compared with SD rats, the total body weight, fat weight and lean body weight of OR rats decreased significantly (P <0.05). OR rats were significantly less obese than SD rats (P <0.05). OR rats at 3 months of age are mainly horizontal activity, vertical activity increased at 6 months of age, so OR rats increased significantly with age (P <0.05). OR rats injected orexin A to increase the role of SPA stronger than the SD rats, the main reason is that OR rat horizontal activity was significantly higher than the vertical activity time. Compared with SD rats, OR rats had high SPA level, light body weight, no significant difference in daytime energy expenditure and SD rats, and more activity in nighttime activities. After OR injections of orexin-A, the high-dose orexin-A in both groups significantly increased SPA (P <0.05) in a dose-dependent manner. For SD rats, only the highest dose of OXA caused SPA to be significantly higher than the control group (P <0.05). After the highest dose of orexin-A injection in both groups, SPA changes in OR rats were more significant than those in SD rats (250 pmol: P <0.05; 500 pmol: P <0.05). Conclusion: Locus coeruleus (LC) orexin-A has an important effect on spontaneous activity in obese rats, and its orexin regulation is associated with obesity resistance.