Yuan Qingjie, Li Yang, Deng Xiaofei, Shi Huawei, Zhao Zhenwu, Wang Chunye, Feng Xuegong, Guo Jianyou, Guo Rongjuan
Beijing Hospital of Integrated Traditional Chinese and Western Medicine, Beijing 100039, China.
Beijing University of Chinese Medicine, Beijing 100029, China.
Evid Based Complement Alternat Med. 2019 Jan 3;2019:6054926. doi: 10.1155/2019/6054926. eCollection 2019.
To clarify the effectiveness and mechanism of the Chinese herbal formula (XPKYF) which is composed of (Xi-Yang-shen), (Yu-Jin), (Shi-Chang-pu), and (Guan-Ye-lian-qiao) in depressed rats.
The rat model of depression was established by chronic unpredictable mild stress (CUMS) method for 6 weeks. Rats were randomly divided into six groups: control group, CUMS group, CUMS+XPKYF (3.6g/kg/d, 7.2g/kg/d, 14.4g/kg/d) groups, and CUMS+sertraline (4.5mg/kg/d) group. The sucrose preference test and the forced swimming test were performed to assess the rats' depression behavior. Mitochondrial ultrastructure was observed by transmission electron microscope and adenosine triphosphate (ATP) content, sodium potassium ATPase (Na/K-ATPase) activity, and mitochondrial respiratory chain complexes activities in hippocampus and gastrocnemius muscle were measured at the 14 and 42 day.
Rats subjected to six weeks of CUMS exhibited decreased sucrose preference ratio and prolonged immobility time. CUMS reduced ATP content in hippocampus, decreased Na/K-ATPase activity and respiratory chain complex I, III, and IV activities in hippocampus and gastrocnemius muscle, and damaged mitochondrial ultrastructure of hippocampus and gastrocnemius muscle. XPKYF at 14.4g/kg, the efficacy trend of which was better than the other drug groups, could prevent the stress-induced depressed behavior changes, inhibit the decrease of Na/K-ATPase activity in hippocampus, inhibit the decrease of respiratory chain complex III activities in hippocampus and gastrocnemius muscle, and protect mitochondria from ultrastructural damage.
Energy deficiency and damaged mitochondrial ultrastructure were found in hippocampus and gastrocnemius muscle of depressed rats established by CUMS. XPKYF could partly reverse alterations in ATP, Na/K-ATPase, and respiratory chain complexes of hippocampus and gastrocnemius muscle and protect mitochondria from ultrastructural damage. This provides another experimental evidence for the clinical application of XPKYF in the treatment of depression.
阐明由西洋参、郁金、石菖蒲和关叶连翘组成的中药复方（XPKYF）对抑郁大鼠的疗效及作用机制。
采用慢性不可预测温和应激（CUMS）法建立大鼠抑郁模型，持续6周。将大鼠随机分为6组：对照组、CUMS组、CUMS+XPKYF（3.6g/kg/d、7.2g/kg/d、14.4g/kg/d）组和CUMS+舍曲林（4.5mg/kg/d）组。进行蔗糖偏好试验和强迫游泳试验以评估大鼠的抑郁行为。在第14天和第42天，用透射电子显微镜观察线粒体超微结构，并测定海马和腓肠肌中三磷酸腺苷（ATP）含量、钠钾ATP酶（Na/K-ATP酶）活性以及线粒体呼吸链复合物活性。
接受6周CUMS处理的大鼠蔗糖偏好率降低，不动时间延长。CUMS降低了海马中的ATP含量，降低了海马和腓肠肌中Na/K-ATP酶活性以及呼吸链复合物I、III和IV的活性，并损害了海马和腓肠肌的线粒体超微结构。14.4g/kg的XPKYF疗效趋势优于其他药物组，可预防应激诱导的抑郁行为变化，抑制海马中Na/K-ATP酶活性的降低，抑制海马和腓肠肌中呼吸链复合物III活性的降低，并保护线粒体免受超微结构损伤。
在CUMS诱导建立的抑郁大鼠的海马和腓肠肌中发现能量缺乏和线粒体超微结构受损。XPKYF可部分逆转海马和腓肠肌中ATP、Na/K-ATP酶和呼吸链复合物的改变，并保护线粒体免受超微结构损伤。这为XPKYF在抑郁症治疗中的临床应用提供了另一实验依据。
