禁食大鼠可能经抑制mTOR减低心肌摄取葡萄糖  

Fasting reduces glucose uptake in rat myocardium via mTOR inhibition

作　　者：周详 蒋帅 王小波 赵汝舟 焦博 张琳 王云英 张园园 余志斌 ZHOU Xiang;JIANG Shuai;WANG Xiao-bo;ZHAO Ru-zhou;JIAO Bo;ZHANG Lin;WANG Yun-Ying;ZHANG Yuan-yuan;YU Zhi-bin(Department of Aerospace Physiology,School of Aerospace Medicine,Air Force Medical University,Xi’an 710032,Shaanxi,China;First Cadet Regiment,School of Basic Medical Sciences,Air Force Medical University,Xi’an 710032,Shaanxi,China;Department of Nuclear Medicine,Xijing Hospital,Air Force Medical University,Xi’an 710032,Shaanxi,China)

机构地区：[1]空军军医大学航空航天医学系航空航天生理学教研室,陕西西安710032 [2]空军军医大学基础医学院一大队一队,陕西西安710032 [3]空军军医大学西京医院核医学科,陕西西安710032

出　　处：《心脏杂志》2022年第2期203-209,共7页Chinese Heart Journal

基　　金：空军军医大学军事助推计划资助(2020AFB008)。

摘　　要：目的确定禁食降低心肌摄取葡萄糖的动态变化过程,探寻禁食降低大鼠心肌摄取葡萄糖能力的可能机制,为阐明禁食提高缺氧耐力作用奠定基础。方法测量不同禁食时间和恢复饮食组雄性SD大鼠体质量、血糖和血酮水平;采用M型超声心动图测量SD大鼠禁食后及恢复饮食后心脏泵血功能;对各组SD大鼠行^(18)F-FDG PET/CT显像,定量观测心肌FDG摄取;检测不同葡萄糖浓度培养心肌细胞的mTOR和AMPK表达与活性。结果SD大鼠体质量随禁食时间延长显著下降,并在恢复饮食24 h后恢复至接近禁食前水平;禁食24 h血糖显著降低,48 h达稳定水平,相反,禁食24 h血酮显著升高,在48 h达稳定水平;在恢复饮食24h后,血糖与血酮均恢复至正常水平。禁食各时间点及恢复饮食后心脏泵血功能均无明显改变。PET/CT显示心肌^(18)F-FDG摄取(SUV ratio)在禁食24 h后显著减低,并在正常饮食24h后恢复。降低培养心肌细胞的葡萄糖浓度,mTOR和AMPK的蛋白表达水平未见改变,但是,mTOR活性降低,AMPK活性增加。结论禁食引起低血糖可直接降低mTOR活性,另一方面,低血糖通过激活AMPK,间接抑制mTOR活性,可能进而抑制心肌对^(18)F-FDG摄取。AIM To investigate the underlying mechanism of blood glucose regulating myocardial ^(18)FFDG uptake in fasting rats.METHODS The body weight,blood glucose and blood ketone levels of male SD rats were measured at different fasting duration and re-feeding groups.M-mode echocardiography was used to measure the cardiac pumping function of rats after fasting.Rats in different fasting groups underwent ^(18)F-FDG PET/CT scanning to observe and quantitatively analyze the myocardial ^(18)F-FDG uptake.The expression and activity of mTOR and AMPK were detected in cardiomyocytes cultured with different glucose concentrations.RESULTS The body weight of rats decreased significantly with the prolonged fasting and returned to approximately pre-fasting level after re-feeding for 24 hours.The blood glucose decreased significantly in the 24h-fasting group and reached a lower and stable level in 48h-fasting and 72h-fasting groups.On the contrary,the blood ketone increased significantly in the 24h-fasting group and reached a higher and stable level in 48h-fasting and 72h-fasting groups.Twenty-four hours after re-feeding,blood glucose and blood ketone were completely reversed.There was no significant difference in cardiac performance between fasting groups and their synchronous control groups.PET/CT imaging showed that myocardial ^(18)F-FDG uptake(SUV ratio)was significantly reduced after 24h-fasting and completely recovered after 24h-refeeding.When the glucose concentration was reduced in cultured cardiomyocytes,the activity of mTOR decreased,but the activity of AMPK increased significantly.CONCLUSION Fasting leads to hypoglycemia which directly inhibits mTOR in the myocardium.On the other hand,activated AMPK by hypoglycemia indirectly inhibits mTOR and the reduction of mTOR activity may decrease the myocardial ^(18)F-FDG uptake in fasting rats.

关 键 词：禁食 血糖 心肌^(18)F-FDG摄取 mTOR蛋白表达 

分 类 号：R541[医药卫生—心血管疾病]