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目的建立抗精神病药奥氮平(olanzapine)诱导的肥胖大鼠模型,探讨茶多酚(TP)的减肥作用及机制。方法健康雌性SD大鼠70只,按体重随机分为正常对照组10只,其余60只灌胃给予奥氮平(1.2 mg/kg)2 w。将造模成功的40只肥胖大鼠随机分为模型组、盐酸西布曲明组(2.5 mg/kg)、茶多酚低(150 mg/kg)、高(300 mg/kg)剂量组,每组10只。动物继续给予奥氮平处理,同时灌胃给予上述药物处理5 w。在处理过程中,测定大鼠的体重、摄食和摄水量。第5 w末时,利用SMART video-tracking system测定大鼠白昼和黑暗时相的自主活动,然后处理大鼠,采用高效液相色谱-电化学检测(HPLC-ECD)法测定下丘脑中去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)、5-羟色胺(5-HT)、3,4-二羟基苯乙酸(DOPAC)、5-羟吲哚乙酸(5-HIAA)的含量。结果 TP处理肥胖大鼠5 w后,饮食量、饮水量和体重明显低于模型大鼠(P<0.05,P<0.01);对动物白昼时相活动与模型组比较无明显影响(P>0.05),但对黑暗时相的平均活动速度和活动距离明显强于模型组(P<0.01);与模型组比较,对下丘脑5-HT含量无明显影响(P>0.05),但明显增加5-HT代谢产物5-HIAA的含量(P<0.01),明显降低DA和DOPAC含量(P<0.01),同时明显增加NE的含量。结论 TP对奥氮平诱导的肥胖大鼠具有抑制饮食量和饮水量、增加活动、降低体重的作用,此作用与其对下丘脑单胺类神经递质的调节有关。
Objective To establish an olanzapine-induced obesity rat model and explore the mechanism of weight loss of tea polyphenols (TP). Methods Seventy healthy female Sprague-Dawley rats were randomly divided into normal control group (n = 10) according to body weight. The remaining 60 orally administered olanzapine (1.2 mg / kg) for 2 weeks. Forty obese rats were randomly divided into model group, sibutramine hydrochloride group (2.5 mg / kg), low tea polyphenols (150 mg / kg) and high (300 mg / kg) Each group of 10. Animals were continued olanzapine treatment, while gavage given the drug treatment 5 w. During the treatment, the body weight, feeding and water intake of the rats were determined. At the end of the 5th wk, SMART video-tracking system was used to measure the autonomic activity of the rat during the day and dark phase. The rats were then treated with HPLC-ECD to determine the normotope in the hypothalamus Norepinephrine (NE), dopamine (DA), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) Results Dietary intake, water intake and body weight of obese rats after 5 w treatment were significantly lower than those of model rats (P <0.05, P <0.01). There was no significant difference in the activity of daylight between TP and model group (P> 0.05 (P <0.01). Compared with the model group, the average 5-HT content in the hypothalamus had no significant effect (P> 0.05), but it was significantly increased by 5 -HT metabolite 5-HIAA (P <0.01), significantly decreased the content of DA and DOPAC (P <0.01), and significantly increased the content of NE. CONCLUSION TP can inhibit the obesity rats induced by olanzapine to reduce the amount of food intake and water intake, increase activity and reduce body weight, which is related to the regulation of monoamine neurotransmitter in the hypothalamus.