摘要
目的:研究仝氏光明丸改善模型大鼠肾阳虚型抑郁症(KYDD)的物质基础和作用机制。方法:通过注射氢化可的松联合CUMS建立大鼠KYDD模型,将SD大鼠随机分为空白组、模型组、氟西汀组和仝氏光明丸低、中、高剂量组,行为学实验(旷场实验、强迫游泳、悬尾实验)考察抑郁情况,ELISA法检测大鼠海马体中神经递质含量及血清T含量,MTT实验考察SH-SY5Y细胞活力。通过UPLC-Q-Extractive Orbitrap MS技术对血清进行入血成分分析,建立入血成分数据库用于网络药理学筛选抗抑郁核心靶点,利用分子对接技术进行抗抑郁机制初步验证。结果:与模型组比较,仝氏光明丸高、中剂量组旷场实验平均活动次数和强迫游泳的游泳时间均提高(P<0.01),悬尾实验静止时间缩短(P<0.01),大鼠海马体中神经递质含量升高(P<0.01),血清中睾酮(T)含量升高(P<0.01)。仝氏光明丸含药血清对Glu诱导损伤的SH-SY5Y细胞具有较好的改善情况(P<0.01)。初步推测出51个入血成分,通过入血成分筛选获得效应靶点29个,核心靶点3个。分子对接结果表明入血成分与核心靶点间具有较好的结合能力。结论:仝氏光明丸能改善KYDD模型大鼠的抑郁情况,发挥抗KYDD作用可能与仝氏光明丸含药血清中的Fuziline、Ginsenoside Rh1、Kaempferitrin和靶点GRM5、SLC6A4、TH有关(结合能<-5 kcal/mol)。
Objective:To investigate the material basis and mechanism of action of TONGs’Guangming Pill in improving kidney yang deficiency depression(KYDD)in rats.Methods:The rat KYDD model was established by injecting hydrocortisone combined with CUMS,and SD rats were randomly divided into blank group,model group,fluoxetine group and TONGs’Guangming Pill low,medium and high dose groups.Behavioral experiments(open field experiment,forced swimming,tail suspension experiment)were used to investigate depression,ELISA to detect neurotransmitter content and serum T content in the hippocampus of rats,and MTT experiment to investigate SH-SY5Y cell viability.The serum was analyzed by UPLC-QExtractive Orbitrap MS technique to establish a database of blood components for the screening of core antidepressant targets by network pharmacology,and the preliminary validation of the antidepressant mechanism was carried out by molecular docking technique.Results:Compared with the model group,the mean number of activities and the swimming time of forced swimming in the open field experiment increased(P<0.01),the resting time in the tail suspension experiment decreased(P<0.01),the neurotransmitter content in the hippocampus increased(P<0.01)and the T content in the serum increased(P<0.01).TONGs’Guangming Pill containing serum showed better improvement in Glu-induced damage to SH-SY5Y cells(P<0.01).Initially,51 blood components were identified,and 29 effector targets and 3 core targets were obtained through blood component screening.The molecular docking results showed that the incoming blood components had a good binding ability with the core targets.Conclusion:TONGs’Guangming Pill can improve depression in rats with the KYDD model,and its anti-KYDD effect may be related to the presence of Fuziline,Ginsenoside Rh1,Kaempferitrin,and the targets GRM5,SLC6A4,and TH in the serum of Tongs’Guangming Pill(binding energy<-5 kcal/mol).
作者
张楠茜
张凯月
吕经纬
王跃龙
申嘉明
张辉
李春楠
孙佳明
ZHANG Nan-xi;ZHANG Kai-yue;LYU Jing-wei;WANG Yue-long;SHEN Jia-ming;ZHANG Hui;LI Chun-nan;SUN Jia-ming(Changchun University of Chinese Medicine,Changchun 130114,China)
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2023年第5期1982-1988,共7页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
吉林省科技发展计划项目(No.YDZJ202201ZYTS177)
国家自然科学基金面上项目(No.82074127)。
关键词
仝氏光明丸
肾阳虚型抑郁症
入血成分
网络药理学
分子对接
TONGs’Guangming Pill
Kidney yang deficiency depression
Blood entry component
Network pharmacology
Molecular docking
