摘要
目的观察逍遥散对抑郁大鼠行为学及其骨骼肌线粒体超微结构和功能的影响。方法将SD大鼠随机分为对照组、模型组、文拉法辛(给予盐酸文拉法辛胶囊35 mg·kg^(-1))组和逍遥散(生药21.2 g·kg^(-1))组,每组12只。除对照组外,采用孤养结合28 d慢性不可预知温和应激(CUMS)建立抑郁模型,造模同时给药,每天1次,连续给药28 d。对大鼠的体质量、糖水偏爱率及旷场实验中的直立次数、穿越格数进行评价;在透射电镜下观察骨骼肌线粒体结构,试剂盒法检测骨骼肌线粒体中腺嘌呤核苷三磷酸(ATP)和线粒体呼吸链复合体(MRCC)Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ水平。结果与对照组比较,模型组大鼠体质量增长显著减缓、糖水偏爱率、直立次数和穿越格数显著减少(P<0.05、0.01);与模型组比较,文拉法辛组和逍遥散组造模第3、4周大鼠体质量显著增加(P<0.05、0.01),文拉法辛组造模第2、3周和逍遥散组造模第1~4周大鼠糖水偏爱率显著升高(P<0.05、0.01),文拉法辛组造模第1、3、4周和逍遥散组造模第3、4周大鼠直立次数显著增加(P<0.05、0.01),文拉法辛组造模第1~4周和逍遥散组造模第3、4周大鼠穿越格数显著增多(P<0.05、0.01)。透射电镜结果发现,与对照组比较,模型组大鼠骨骼肌线粒体数目减少、空泡变性及形态肿胀;与模型组比较,文拉法辛组和逍遥散组的大鼠骨骼肌线粒体结构和功能损伤较轻。与对照组比较,模型组大鼠骨骼肌中的MRCCⅠ、Ⅱ、Ⅲ、Ⅳ、Ⅴ和ATP水平显著下降(P<0.05、0.01);与模型组比较,文拉法辛组MRCCⅠ、Ⅱ、Ⅳ水平,逍遥散组MRCCⅠ、Ⅱ、Ⅲ、Ⅳ、Ⅴ和ATP水平均显著升高(P<0.05、0.01)。结论抑郁大鼠出现骨骼肌线粒体结构和功能损伤,可能是引起抑郁大鼠产生疲劳的原因之一;逍遥散可通过保护骨骼肌线粒体结构和功能进而改善大鼠抑郁症状。
Objective To observe the effects of Xiaoyaosan on the behavior of depressed rats and their skeletal muscle mitochondrial ultrastructure and function.Methods SD rats were randomly divided into control group,model group,venlafaxine hydrochloride capsule 35 mg·kg^(-1) group and Xiaoyao powder(crude drug 21.2 g·kg^(-1))group,with 12 rats in each group.Except for the control group,the depression model was established by solitary confinement combined with chronic unpredictable mild stress(CUMS)for 28 days.The model was administered simultaneously,once a day,for 28 days.In this experiment,behavioral indicators such as body weight,sugar-water preference,and the number of standing uprights and number of crossings in the open field experiment were evaluated.The structure of skeletal muscle mitochondria was observed under transmission electron microscope,and the levels of adenine nucleoside triphosphate(ATP)and mitochondrial respiratory chain complex(MRCC)Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ in skeletal muscle mitochondria were detected by kit method.Results Compared with control group,the weight gain of model group was significantly slowed down,the sugar water preference rate,the number of upright and the number of crossing grids were significantly decreased(P<0.05,0.01).Compared with model group,the body weight of rats in venlafaxine group and Xiaoyaosan group was significantly increased at the 3rd and 4th week of modeling(P<0.05,0.01),and the sugar water preference rate of rats in venlafaxine group was significantly increased at the 2nd and 3rd week of modeling and Xiaoyaosan group was significantly increased at the 1st to 4th week of modeling(P<0.05,0.01).The upright times of rats in venlafaxine group at 1,3 and 4 weeks and Xiaoyaosan group at 3 and 4 weeks were significantly increased of modeling(P<0.05,0.01),and the crossing grid number of rats in venlafaxine group at 1 to 4 weeks of modeling and Xiaoyaosan group at 3 and 4 weeks of modeling were significantly increased(P<0.05,0.01).The results of lens showed that compared with control group,the number of mitochondria in skeletal muscle of rats in model group decreased,vacuolar degeneration and morphological swelling.Compared with the model group,the skeletal muscle mitochondria of rats in the venlafaxine group and Xiaoyaosan group had no significant change with the control group.Compared with the control group,the levels of MRCCⅠ,Ⅱ,Ⅲ,Ⅳ,Ⅴand ATP in skeletal muscle of the model group were significantly decreased(P<0.05,0.01).Compared with model group,the levels of MRCCⅠ,ⅡandⅣin venlafaxine group,and the levels of MRCCⅠ,Ⅱ,Ⅲ,Ⅳ,Ⅴand ATP in Xiaoyaosan group were significantly increased(P<0.05,0.01).Conclusion The structure and function of skeletal muscle mitochondria are damaged in CUMS rats,which may be one of the reasons for fatigue in CUMS rats.Xiaoyaosan can improve depressive symptoms in rats by protecting the structure and function of skeletal muscle mitochondria.
作者
冀翠
韩雨梅
赵伟迪
刘相玉
令狐婷
田俊生
秦雪梅
JI Cui;HAN Yumei;ZHAO Weidi;LIU Xiangyu;LINGHU Ting;TIAN Junsheng;QIN Xuemei(School of Physical Education,Shanxi University,Taiyuan 030006,China;Modern Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan 030006,China)
出处
《药物评价研究》
CAS
2022年第9期1763-1769,共7页
Drug Evaluation Research
基金
国家自然科学基金资助项目(82074147)。
关键词
逍遥散
抑郁症
骨骼肌
线粒体超微结构
线粒体功能
Xiaoyaosan
depression
skeletal muscle
mitochondrial ultrastructure
mitochondrial function
