摘要
目的探究皮质酮(corticosterone,CORT)诱导小鼠静息能量代谢率(resting metabolic rate,RMR)改变的趋势和相关机制,观察经典补肾方剂知柏地黄丸和金匮肾气丸的干预作用。方法64只实验小鼠随机分为短期(Day 8)和长期(Day 56)2批,每批随机分为4组:模型组、知柏地黄丸组、金匮肾气丸组小鼠给予含皮质酮无菌饮用水,空白对照组小鼠给予含1%无水乙醇的无菌饮用水。知柏地黄丸组、金匮肾气丸组小鼠中药灌胃干预。造模及中药干预期间动态监测各组小鼠RMR。透射电镜观察各组肝、肌肉组织线粒体形态;免疫荧光观察各组肝、肌肉组织TR表达水平,检测各组肝、肌肉组织MDA、ATP水平,各组血清ACTH、TSH、INS、T3、T4、FT3、FT4、8-OHdG、FGF-21、GDF-15、L-乳酸、丙酮酸水平。结果与空白对照组比较,模型组小鼠肝、肌肉组织线粒体形态受损、TR表达量降低。短期批次,模型组小鼠RMR、肝组织ATP含量、血清T4、ACTH、INS水平显著升高,血清FGF-21、TSH水平、肝组织MDA含量显著降低,长期批次,模型组小鼠RMR、血清8-OhdG、INS水平,肝、肌肉组织ATP含量显著降低,血清FGF-21、GDF-15、T3、T4、FT3、FT4水平,肝、肌肉组织MDA含量显著升高。与模型组比较,短期批次,知柏地黄丸组小鼠RMR、血清L-乳酸水平显著降低,血清8-OHdG水平、肌肉组织TRα表达量显著升高。金匮肾气丸组小鼠肌肉组织线粒体形态改善、TRα表达量、血清FGF-21水平显著升高,血清L-乳酸、FT4、肝组织ATP水平显著降低。长期批次,知柏地黄丸组血清FGF-21显著降低。金匮肾气丸组RMR、肝组织ATP水平、肌肉组织TRα表达量显著升高,血清FGF-21、GDF-15、T3、FT4水平、肌肉组织MDA水平显著降低。结论CORT诱导小鼠RMR随干预时间出现先升高、再降低的趋势。CORT短期应用时,知柏地黄丸显著降低小鼠RMR,长期应用时,金匮肾气丸显著升高小鼠RMR。其机制可能与组织线粒体损伤、甲状腺素分泌、甲状腺素受体表达相关。
Objective To explore the change trend and related mechanism of resting metabolic rate induced by corticosterone in mice,and observe the intervention effects of Zhibai Dihuang Pill and Jinkui Shenqi pill.Methods Sixty-four mice were randomly divided into short-term and long-term groups,and each group was randomly divided into four groups.Mice in CORT group,ZBDH group and JKSQ group were given sterile drinking water containing corticosterone,and mice in Ctrl group were given sterile drinking water containing 1%anhydrous ethanol.Mice in ZBDH group and JKSQ group were given Chinese medicine by gavage.RMR of mice in each group was dynamically monitored during modeling and Chinese medicine intervention.The morphology of mitochondria in liver and muscle were observed by transmission electron microscope.The TR expression level in liver and muscle tissues of each group was observed by immunofluorescence,and MDA and ATP levels were detected in liver and muscle tissues of each group.levels of ACTH,TSH,INS,T3,T4,FT3,FT4,8-OHdG,FGF-21,GDF-15,L-lactic acid and pyruvic acid in serum were also detected.Results Compared with Ctrl group,the mitochondrial morphology of liver and muscle tissues in CORT group was damaged,and the expression of TR was decreased.In short-term(Day 8),RMR,ATP in liver,serum T4,ACTH and INS levels were significantly increased in the CORT group,while serum FGF-21,TSH levels and MDA in liver were significantly decreased.In long term(Day 56),RMR,serum 8-OhdG,INS,and ATP in liver and muscle were significantly decreased in the CORT group,serum FGF-21,GDF-15,T3,T4,FT3,FT4,MDA in liver and muscle were significantly increased.Compared with CORT group,in short term,RMR,serum L(+)-lactate in ZBDH group were significantly decreased,while serum 8-OHdG and the expression of TRαin muscle were significantly increased.In JKSQ group,the mitochondrial morphology of muscle tissue was improved,the expression of TRαand serum FGF-21 were significantly increased,while serum L(+)-lactic acid,FT4 and ATP in liver were significantly decreased.In long term,serum FGF-21 was significantly lower in ZBDH group,and in JKSQ group,RMR,ATP in liver tissue and TRαexpression in muscle were significantly increased,while the levels of FGF-21,GDF-15,T3,FT4 in serum and MDA in muscle tissue were significantly decreased.Conclusion CORT induced RMR to increase first and then decrease with the intervention time.In the short term,Zhibai Dihuang Pill significantly decreased RMR in mice,while in the long term,Jinkui Shenqi Pill significantly increased RMR.The mechanism may be related to mitochondrial injury,thyroxine secretion and thyroxine receptor expression.
作者
贾雨欣
陈丹丹
胡吉梦
邓晓红
黄建华
JIA Yuxin;CHEN Dandan;HU Jimeng;DENG Xiaohong;HUANG Jianhua(Institute of Integrated Traditional Chinese and Western Medicine,Huashan Hospital Affiliated to Fudan University,Shanghai 200040,China;Department of Urology,Huashan Hospital Affiliated to Fudan University,Shanghai 200040,China)
出处
《中国实验动物学报》
北大核心
2025年第7期1043-1052,共10页
Acta Laboratorium Animalis Scientia Sinica
关键词
皮质酮
静息能量代谢率
线粒体
甲状腺素
corticosterone
resting metabolic rate
mitochondria
thyroxine Conflicts of Interest:The authors declare no conflict of interest.
