目的 觀察逍遙散對抑郁大鼠行為學(xué)及其骨骼肌線粒體超微結(jié)構(gòu)和功能的影響。方法 將SD大鼠隨機分為對照組、模型組、文拉法辛（給予鹽酸文拉法辛膠囊35 mg·kg^-1）組和逍遙散（生藥21.2 g·kg^-1）組，每組12只。除對照組外，采用孤養(yǎng)結(jié)合28 d慢性不可預(yù)知溫和應(yīng)激（CUMS）建立抑郁模型，造模同時給藥，每天1次，連續(xù)給藥28 d。對大鼠的體質(zhì)量、糖水偏愛率及曠場實驗中的直立次數(shù)、穿越格數(shù)進行評價；在透射電鏡下觀察骨骼肌線粒體結(jié)構(gòu)，試劑盒法檢測骨骼肌線粒體中腺嘌呤核苷三磷酸（ATP）和線粒體呼吸鏈復(fù)合體（MRCC）I、Ⅱ、III、IV、V水平。結(jié)果 與對照組比較，模型組大鼠體質(zhì)量增長顯著減緩、糖水偏愛率、直立次數(shù)和穿越格數(shù)顯著減少（P＜0.05、0.01）；與模型組比較，文拉法辛組和逍遙散組造模第3、4周大鼠體質(zhì)量顯著增加（P＜0.05、0.01），文拉法辛組造模第2、3周和逍遙散組造模第1～4周大鼠糖水偏愛率顯著升高（P＜0.05、0.01），文拉法辛組造模第1、3、4周和逍遙散組造模第3、4周大鼠直立次數(shù)顯著增加（P＜0.05、0.01），文拉法辛組造模第1～4周和逍遙散組造模第3、4周大鼠穿越格數(shù)顯著增多（P＜0.05、0.01）。透射電鏡結(jié)果發(fā)現(xiàn)，與對照組比較，模型組大鼠骨骼肌線粒體數(shù)目減少、空泡變性及形態(tài)腫脹；與模型組比較，文拉法辛組和逍遙散組的大鼠骨骼肌線粒體結(jié)構(gòu)和功能損傷較輕。與對照組比較，模型組大鼠骨骼肌中的MRCC Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ和ATP水平顯著下降（P＜0.05、0.01）；與模型組比較，文拉法辛組MRCC Ⅰ、Ⅱ、Ⅳ水平，逍遙散組MRCC Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ和ATP水平均顯著升高（P＜0.05、0.01）。結(jié)論 抑郁大鼠出現(xiàn)骨骼肌線粒體結(jié)構(gòu)和功能損傷，可能是引起抑郁大鼠產(chǎn)生疲勞的原因之一；逍遙散可通過保護骨骼肌線粒體結(jié)構(gòu)和功能進而改善大鼠抑郁癥狀。

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 MRCC Ⅰ, Ⅱ, Ⅲ, Ⅳ, Ⅴ and ATP in skeletal muscle of the model group were significantly decreased (P < 0.05, 0.01). Compared with model group, the levels of MRCC Ⅰ, Ⅱ and Ⅳ in venlafaxine group, and the levels of MRCC Ⅰ, Ⅱ, Ⅲ, Ⅳ, Ⅴ and 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.

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國家自然科學(xué)基金資助項目（82074147）