Ghrelin、melanotan-Ⅱ以及胆囊收缩素对下丘脑双侧室旁核损伤大鼠摄食的影响  

Effects of ghrelin,melanotan-Ⅱ and cholecystokinin on food intake in rats with paraventricular nucleus lesions

作　　者：王俊波 全胜[1] 袁张根 董静尹[1] 张大勇 凌树才[2] 

机构地区：[1]浙江大学城市学院医学与生命科学学院临床医学系,杭州310015 [2]浙江大学医学院人体解剖学与组织胚胎学系,杭州310058

出　　处：《解剖学报》2010年第5期649-653,共5页Acta Anatomica Sinica

基　　金：国家自然科学基金(30570586);浙江省自然科学基金(Y207159)资助

摘　　要：目的探讨大鼠下丘脑双侧室旁核(PVN)损伤引起的过食和肥胖的产生机制。方法 Wistar雄性大鼠36只,通过电损伤下丘脑双侧PVN使大鼠产生过食和肥胖,检测ghrelin、melanotan-II(MT-II,一种合成的α-黑色素细胞刺激素——α-MSH的结构同源体)以及胆囊收缩素-8(CCK-8)摄食作用的改变。结果双侧PVN损伤后大鼠的体重和摄食量明显增加,显示出过食和肥胖,手术后1周,外周给与Ghrelin,3～4h后PVN损伤组比伪损伤组的摄食量增加明显,Ghrelin显示出更强的刺激摄食的作用;中枢给予MT-Ⅱ可明显抑制24h节食大鼠的食物摄取,然而PVN损伤后MT-II对24h节食大鼠摄食的抑制作用减弱甚至消失;外周给予CCK-8可明显抑制大鼠各时间段的摄食作用,PVN损伤组和伪损伤组之间未见明显差异。结论大鼠下丘脑双侧PVN损伤引起的过食和肥胖可能与增强的ghrelin对摄食的刺激作用和(或)α-MSH受体的破坏有关。Objective To investigate the mechanism of hyperphagia and obesity induced by bilateral lesions of the hypothalamic paraventricular nuclei （PVN）. Methods Wistar male rats （36 rats） were used. After bilateral electrolytic lesions of the PVN, we measured the effects of ghrelin, melanotan-II （ MT-II, a synthetic structural homologue of alphamelanocyte-stimulating hormone, α-MSH） and cholecystokinin-8 （CCK-8） on food intake in rats with PVN lesions. Results After bilateral electrolytic lesions of the PVN, the body weight and food intake were significantly increased, showing hyperphagia and obesity. After 1 week of bilateral electrolytic lesions of the PVN, the rats were given ghrelin and CCK-8 intraperitoneally, or intracerebroventricular infusion of MT-II. We measured the cumulative food intake （FI） for 4 hours after ghrelin injection in rats fed ad lib, and the changes in FI at 15min, 30min, 1 hour and 2 hours after administration of MT-II and CCK-8 in rats fasted for 24 hours. Ghrelin significantly increased cumulative FI, with maximal response 3 hours and 4 hours after injection, and at these times, the FI of PVN-lesioned rats was greater than that of shamoperated rats. MT-II decreased FI in sham-operated, but not in PVN-lesioned rats. CCK-8 decreased FI at each time point in all groups, there was no difference between PVN-lesioned and sham-operated rats. Conclusion The hyperphagia and obesity induced by PVN lesions might be related to an increased orexigenic action of ghrelin due to the destruction of α- MSH receptors.

关 键 词：GHRELIN Α-黑色素细胞刺激素 melanotan-II 胆囊收缩素 室旁核 摄食 电损伤 大鼠 

分 类 号：R338.2[医药卫生—人体生理学]