冰片对交泰丸在抑郁模型大鼠药效学、主要活性成分药动学及脑组织分布的影响  

Effect of Borneol on Pharmacodynamics,Pharmacokinetics and Brain Tissue Distribution of Main Active Ingredients of Jiaotaiwan in Depression Model Rats

作　　者：于美双 戴国梁[1] 杭华茜 叶峪 王一然 邵雪文 居文政[1] YU Meishuang;DAI Guoliang;HANG Huaxi;YE Yu;WANG Yiran;SHAO Xuewen;JU Wenzheng(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]南京中医药大学附属医院,南京210029

出　　处：《中国实验方剂学杂志》2024年第24期18-27,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：江苏省基础研究计划面上项目(BK20211394);江苏省医学重点实验室项目(ZDXYS202209);江苏省重点研发计划社会发展项目(BE2023790);江苏省中医药科技发展计划面上项目(MS2021011)。

摘　　要：目的:探讨交泰丸与冰片联用时,对脂多糖(LPS)诱导抑郁模型大鼠药效学,以及7种主要成分药代动力学及脑组织分布的影响。方法:将40只SD大鼠随机分为空白组、模型组、氟西汀组(10 mg·kg^(-1))、交泰丸组(1.50 g·kg^(-1))、交泰丸冰片联用组(交泰丸1.50 g·kg^(-1)+冰片0.05 g·kg^(-1)),每组8只。除空白组外采用腹腔注射LPS建立抑郁模型,各组分别灌胃给予相应药物或等体积纯水,连续14 d。采用糖水偏好实验、旷场实验及强迫游泳实验评估大鼠的抑郁状态;采用酶联免疫吸附测定法(ELISA)检测大鼠血清中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)水平;苏木素-伊红(HE)和尼氏(Nissl)染色观察大鼠海马组织神经元形态变化。取行为学实验后的交泰丸组和交泰丸冰片联用组,分别于灌胃后在设置的时间点采血,采用超高效液相色谱-三重四极杆串联质谱法(UPLC-QqQ-MS/MS)测定血浆中药根碱、表小檗碱、黄连碱、巴马汀、小檗碱、木兰花碱、小檗红碱的含量,采用DAS 3.2.2软件对各成分药代动力学参数进行分析。采血完成后冰上快速取脑,采用UPLC-QqQMS/MS比较7种成分在脑组织中的含量变化。结果:与空白组比较,模型组大鼠糖水偏好率降低、旷场总路程减少、游泳不动时间延长,血清中炎症因子表达升高(P<0.01);与模型组比较,各给药组大鼠糖水偏好率增加、旷场总路程增加、游泳不动时间缩短,交泰丸组和交泰丸冰片联用组大鼠血清中炎症因子表达降低(P<0.05,P<0.01)。病理观察结果显示,交泰丸组和交泰丸冰片联用组均对海马神经元有一定保护作用。药动学结果显示,与交泰丸组比较,交泰丸冰片联用组中小檗碱、表小檗碱的药时曲线下面积(AUC_(0-t)、AUC_(0-∞))、达峰浓度(C_(max))、平均稳态血药浓度(C_(av))增加(P<0.05,P<0.01),黄连碱的AUC_(0-t)、AUC_(0-∞)、平均驻留时间(MRT_(0-∞))、C_(av)增加Objective:To investigate the pharmacodynamics,pharmacokinetics and brain distribution of seven main components of Jiaotaiwan alone and Jiaotaiwan combined with borneol in lipopolysaccharide(LPS)-induced depression rats.Method:Rats were randomly divided into the control group,model group,fluoxetine group(10 mg·kg^(-1)),Jiaotaiwan group(1.5 g·kg^(-1))and combination group(1.5 g·kg^(-1)of Jiaotaiwan+0.05 g·kg^(-1)of borneol),with 8 rats in each group.Except for the control group,the depression model was established by intraperitoneal injection of LPS for 7 consecutive days,and each group was given the corresponding drugs or the same volume of pure water by gavage for 14 consecutive days.The behavioral indicators and levels of serum inflammatory factors[interleukin-1β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)]of rats in each group were compared.The morphological changes of hippocampal neurons were observed by hematoxylin-eosin(HE)and Nissl staining.After the behavioral tests of sucrose preference,open field and forced swimming were completed,blood samples were collected from Jiaotaiwan group and combination group at the set time points after gavage,the contents of seven components in plasma were determined by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLCQqQ-MS/MS),and the pharmacokinetic parameters of each component were analyzed by DAS 3.2.2.Brains were rapidly removed on ice after blood collection was completed,and UPLC-QqQ-MS/MS was used to compare the content changes of the 7 components in brain tissue.Result:Compared with the control group,rats in the model group showed decreased sucrose preference rate and total distance of open field,prolonged swimming immobility time,and increased expression of inflammatory factors in serum(P<0.01).Compared with the model group,the sucrose preference rate and total distance of open field were increased,and the swimming immobility time was shortened in the rats of each administration group,and the expression of inflammator

关 键 词：交泰丸 冰片 抑郁 药动学 药效学 组织分布 

分 类 号：R22[医药卫生—中医基础理论] R28[医药卫生—中医学] O657[理学—分析化学] R969.1[理学—化学] R971