[关键词]
[摘要]
目的 研究逍遥散对抑郁大鼠运动能力及肝脏线粒体结构和功能的影响。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35mg·kg-1)组和逍遥散(生药21.2g·kg-1)组,除对照组外,采用慢性不可预知温和应激(CUMS)建立抑郁模型,于造模同时ig给药,连续28d,每周称体质量。造模结束后进行旷场实验、糖水偏好实验、爬杆实验和转棒实验行为学测试;通过透射电镜观察肝脏线粒体超微结构;通过试剂盒测定血清睾酮、皮质酮水平和线粒体腺嘌呤核苷三磷酸(ATP)和线粒体呼吸链复合体(MRCC)I、III、IV、V水平。结果 与对照组比较,模型组大鼠体质量增长缓慢(P<0.01),糖水偏爱率、旷场实验的穿越格数及直立次数、爬杆实验得分和转棒实验在棒时间均显著下降(P<0.05、0.01);血清皮质酮水平显著增加(P<0.05),睾酮水平和睾酮-皮质酮比值(T/C)显著降低(P<0.05、0.01);大鼠肝脏线粒体数目减少,外膜模糊,基质疏松;肝脏线粒体ATP水平及MRCCⅠ、Ⅲ、Ⅳ、Ⅴ活性降低(P<0.05、0.01)。与模型组比较,逍遥散组大鼠体质量显著增加(P<0.05),旷场实验穿越格数和直立次数增加(P<0.05、0.01),糖水偏好率显著增高(P<0.05),爬杆实验得分显著增加(P<0.01),转棒实验的在棒时间显著延长(P<0.05);血清睾酮水平显著升高(P<0.05),皮质酮水平显著降低(P<0.05),T/C显著升高(P<0.01);大鼠肝脏线粒体嵴清晰,结构较为完整;肝脏线粒体ATP水平和MRCCⅠ、Ⅴ活性显著增加(P<0.05)。结论 逍遥散能够显著改善CUMS大鼠肝脏线粒体形态和功能,提高其运动能力,发挥抗抑郁作用。
[Key word]
[Abstract]
Objective This study aims to clarify the effects of Xiaoyao San on exercise capacity and liver mitochondrial structure and function in depressed rats. 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. Except for the control group, the depression model was established by chronic unpredictable mild stress (CUMS) for 28 days. Rats were administered simultaneously, once a day, for 28 days during modeling. The rats were weighed weekly. After modeling, behavioral tests such as open field experiment, sugar-water preference experiment, pole test and rotarod test were performed, liver mitochondrial ultrastructure was observed by transmission electron microscopy. Serum levels of testosterone and corticosterone, mitochondrial adenine nucleoside triphosphate (ATP) and mitochondrial respiratory chain complex (MRCC) I, III, IV, V were determined by the kits. Results Compared with control group, rats in model group had slow body weight gain (P<0.01), sugar-water preference rate, number of crossing and rearing, score of pole test and time of rotarod test were significantly decreased (P<0.05 and 0.01), serum corticosterone level was significantly increased (P<0.05), and testosterone level and testosterone/corticosterone ratio (T/C) were significantly decreased (P<0.05 and 0.01). The electron microscopic results showed that the number of mitochondria in the liver of rats was reduced, the outer membrane was blurred and the matrix was loose in model group compared with control group. The results of the kits showed that the liver mitochondrial adenine nucleoside triphosphate (ATP) content and respiratory chain complex I, III, IV and V activities were decreased in model group rats compared with control group (P<0.05 and 0.01). Compared with model group, the body mass of rats in Xiaoyao San group was significantly increased (P<0.05), the number of crossing cells and the number of upright times in open field experiment were increased (P<0.05, 0.01), the sugar water preference rate was significantly increased (P<0.05), the score in pole climbing experiment was significantly increased (P<0.01), the time in rod spinning experiment was significantly extended (P<0.05), corticosterone levels decreased (P<0.05) and testosterone levels and T/C increased (P<0.05). After the intervention of Xiaoyao San, the mitochondrial cristae were clear and the structure was more complete in the liver of rats. ATP content and respiratory chain complex I and V activities were increased after the intervention of Xiaoyao San compared with model group (P<0.05). Conclusion It is concluded that Xiaoyao San can significantly improve the morphology and function of liver mitochondria, enhance exercise capacity and exert antidepressant effects in CUMS rats.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金资助项目(82074147);山西省基础研究计划项目(202103021224027)