目的研究缺氧大鼠下丘脑Ⅰ型大麻素受体(cannabinoid receptor typeⅠ,CB1)的表达变化及其与摄食量的关系。方法 54只雄性SD大鼠按随机数字表法分为3组(每组18只):平原对照组、缺氧1 d组和缺氧7 d组。缺氧组大鼠置模拟海拔5 000 m低压舱中,平原对照组大鼠置平原饲养。记录各组大鼠摄食量,蛋白免疫印迹法和免疫组化法观察各组大鼠下丘脑CB1受体和c-Fos蛋白表达变化。结果与平原对照组[(15.5±2.7)g]大鼠相比,缺氧1 d组大鼠摄食量[(4.9±0.7)g]显著减少(P〈0.05),同时大鼠下丘脑CB1和c-Fos阳性细胞数量和蛋白表达量显著减少;缺氧1 d组大鼠弓状核(arcuate nucleus,ARC)、下丘脑腹外侧区(later hypothalamic area,LH)和下丘脑腹内侧核(ventromedial hypothalamic nucleus,VMH)CB1受体、c-Fos表达较平原对照组显著降低;随着缺氧时间的延长,动物摄食量逐日增加,缺氧3~7 d时的摄食量与平原对照组大鼠相当;缺氧7 d组大鼠下丘脑CB1受体和c-Fos阳性细胞数量和蛋白表达量与平原对照组大鼠比较,差异无统计学意义(P〉0.05)。结论急性缺氧大鼠摄食减少可能与弓状核、下丘脑腹外侧区和下丘脑腹内侧核CB1受体和c-Fos表达减少相关。
Objective To study the relationship between the hypothalamic expression of cannabinoid receptor type Ⅰ( CB1) and food intake during hypoxia exposure in rats. Methods Adult SD rats were randomly divided into 3 groups: normal group( N),2-day hypoxia exposure group( H1d) and 7-day hypoxia exposure group( H7d). The rats of the hypoxia groups were put into a hypobaric chamber simulating 5 000-meter high altitude for 1 or 7 d,and the food intake and body weight of each group were recorded. The expression levels of CB1 and c-Fos in the hypothalamus were detected by Western blotting and immuohistochemical assay. Results After exposure to hypoxia,the food intake of the H1 d group was lower than that of the N group significantly( 4. 9 ± 0. 7 vs 15. 5 ± 2. 7 g,P〈 0. 05). The level of CB1 in the arcuate nucleus( ARC),later hypothalamic area( LH) and ventromedial hypothalamic nucleus( VMH) was reduced obviously,and the expression of c-Fos in the ARC,LH and VMH was decreased,too. The food intake was increased along with the days of exposure to hypoxia,and in 3 ~ 7 d after hypoxia exposure,the rats in the H7 d group had the food intake similar with the N group. The levels of CB1 and c-Fos had no significant changes between the H7 d group and the N group. Conclusion The down-regulation of CB1 and c-Fos in the ARC,LH and VMH may be closely associated with the food intake decrease induced by acute exposure to hypoxia.