醒脾解郁方对抑郁大鼠行为学及海马与骨骼肌线粒体超微结构的影响

目的探讨醒脾解郁方对抑郁模型大鼠行为学及海马与骨骼肌线粒体超微结构的影响。方法将Wister大鼠平均分成5组,即空白对照组、模型组、舍曲林组、醒脾解郁高、低剂量组。采用28 d慢性不可预见应激(CUS)建立抑郁模型,治疗各组给予相应药物灌胃,连续给药28 d。模型组、空白对照组以蒸馏水代替药液。以大鼠体重变化、糖水偏爱及旷场实验进行抑郁行为学评价,采用透射电镜观察大鼠海马神经元、骨骼肌细胞线粒体超微结构变化。结果与空白对照组相比,模型组大鼠体重增长缓慢、糖水偏爱率下降、旷场运动总路程减少(P0.01);与模型组相比,醒脾解郁高、低剂量组及舍曲林组大鼠体重、糖水偏爱率、旷场中运动总路程均明显增加(P0.05)。透射电镜观察结果:模型组海马神经元及骨骼肌细胞均出现线粒体数目减少、形态肿胀、空泡变性,内嵴排列紊乱甚至溶解消失。醒脾解郁高剂量组海马神经元及骨骼肌线粒体接近正常,未见肿胀及空泡变性;醒脾解郁低剂量组与舍曲林组海马神经元及骨骼肌的线粒体形态轻度肿胀,内嵴部分紊乱。结论慢性应激导致抑郁的发生中,海马与骨骼肌均会出现线粒体结构的损伤,这可能是抑郁症极度疲劳和多系统症状的关键因素之一;醒脾解郁方能改善大鼠抑郁行为学及线粒体结构损伤,其中高剂量组一定程度上比舍曲林组有效果更好的趋势。

Effects of Xingpi Jieyu Fang on behavior and mitochondria ultrastructure of hippocampus and skeletal muscle in depressed rats

Objective To explore the effects of Xingpi Jieyu Fang (XPJYF, Spleen-invigorating Depression-relieving Formula) on behaviors and mitochondria ultrastructure of hippocampus neurons and skeletal muscle in depressed rats.Methods Wister rats were randomly divided into five groups: blank control group, model group, sertraline group, XPJYF high-dose and low-dose groups.Chronic unpredictable stress (CUS)was applied to establish depression models in rats for 28 days.Intragastric gavage was used to offer corresponding medication in treatment groups or distilled water in model and blank control groups.Weight change, sugar/water preference test and open-field test were used to evaluate depressive behavior in rats.Changes in ultrastructure of mitochondria in hippocampus neurons and skeletal muscles of depressive rats were measured by using transmission-electron microscope.Results Compared with the blank control group, weight gain in model group rats was significantly slowed while the sugar/water preference rate and total moving distance of open-field test decreased significantly (P<0.01).The number of mitochondria in hippocampal neurons and skeletal muscle in the model group was also reduced with irregular swelling, fractured and fuzzy cristae as well as vacuolar degeneration.under the transmission-electron microscope Compared with the model group, body weight, total sugar/water preference rate, and total moving distance of open-field test in XPJYF high-dose, low-dose group and sertraline group were significantly increased (P<0.01).No swelling or vacuolar degeneration were observed in mitochondria of hippocampal neurons and skeletal muscle in XPJYF high-dose group, which were close to the normal level.Hippocampal neuron and skeletal muscle mitochondria of XPJYF low-dose group and sertraline group were slightly swollen with partly fractured and fuzzy cristae.Conclusion The mitochondria structure of hippocampal neurons and skeletal muscle were damaged in depression induced by chronic stress, which may be a key factor in severe fatigue and symptoms involving multiple systems.Xingpi Jieyu formula could improve depressive behavior and mitochondria structure damage in depressed rats.To some extent, the effects of high-dose Xingpi Jieyu formula were better than sertraline in improving depression of rats.