下丘脑LHA-VMH Ghrelin信号通路对肥胖大鼠摄食选择、胃肠道运动及自发活动的影响及机制研究

目的:探究下丘脑外侧区(LHA)-腹内侧核(VMH)ghrelin信号通路对肥胖大鼠的摄食选择、胃肠道运动及自发活动的影响。方法:采用免疫组织化学方法检测大鼠LHA中ghrelin受体的表达;观察LHA注射ghrelin对大鼠摄食选择胃肠道运动及自发活动的影响;电损毁VMH,观察LHA注射ghrelin对大鼠摄食的影响。结果:免疫组化结果显示,大鼠下丘脑LHA中存在ghrelin受体,且LHA-VMH之间存在纤维投射;大鼠LHA微量注射ghrelin后,肥胖(DIO)大鼠及肥胖抵抗(DR)大鼠的正常饮食、高脂饮食及高糖饮食均高于正常大鼠,但预注射ghrelin受体拮抗剂D-Lys3]-GHRP-6 (DLS)能够阻断这种作用;而电损毁大鼠VMH,显著减弱了ghrelin对正常大鼠、DIO大鼠及DR大鼠的促摄食作用。大鼠LHA微量注射ghrelin后,正常大鼠、DIO大鼠及DR大鼠的自发活动中,X轴、Y轴方向上的活动增加,且总活动增加,但Z轴方向上活动无明显改变;此外,LHA注射ghrelin,DIO大鼠及DR大鼠的胃肠道转运速率明显加快,且DR大鼠胃肠道转运速率增加更为明显,而预注射ghrelin受体拮抗剂D-Lys3]-GHRP-6(DLS)显著阻断ghrelin的促胃肠道转运作用。结论:下丘脑LHA-VMH ghrelin信号通路参与调节正常大鼠、DIO及DR大鼠的摄食选择、胃肠道运动及自发活动。

Effect of Hypothalamic LHA Injection of Ghrelin on the Feeding and Energy Metabolism in Rats and Its Mechanisms

ABSTRACT Objective: To explore the effects of ghrelin signaling pathway in the lateral hypothalamic (LHA)-ventral medial nucleus (VMH) on feeding choice, gastrointestinal motility and spontaneous activity in obese rats. Methods: The expression of ghrelin receptor in rat LHA was detected by immunohistochemistry. To observe the effect of LHA injection of ghrelin on the movement and spontaneous activity of gastrointestinal tract in rats. The VMH was destroyed by electrical damage, and the effect of LHA injection of ghrelin on the feeding of rats was observed. Results: Immunohistochemistry showed that there was ghrelin receptor in the LHA, and there was fiber projection from LHA to VMH; After microinjection of ghrelin into LHA, the normal diet, high-fat diet and high-glucose diet of obese (DIO) rats and obesity-resistant(DR) rats were higher than normal rats, but pre-injected with ghrelin receptor antagonistD -Lys3]-GHRP-6 (DLS) can block this effect; The electric damage of rat VMH significantly attenuated the feeding effect of ghrelin on normal rats, DIO rats and DR rats. After microinjection of ghrelin into LHA, the activities in the X-axis and Y-axis increased in the spontaneous activities of normal rats, DIO rats and DR rats, and the total activity increased, but the activity in the Z-axis direction did not change significantly; In addition, the gastrointestinal transit rate of LHA injected ghrelin, DIO rats and DR rats was significantly accelerated, and the gastrointestinal transit rate of DR rats increased more significantly, while pre-injection of ghrelin receptor antagonistD-Lys3]- GHRP-6 (DLS) significantly blocked the gastrointestinal transit of ghrelin. Conclusion: The hypothalamic LHA-VMH ghrelin signaling pathway can be involved in the regulation of feeding selection, gastrointestinal motility and spontaneous activity in male SD rats.