冰片对岩黄连总碱在抑郁症模型大鼠中药效学和药动学的影响  

Effects of borneol on pharmacodynamics and pharmacokinetics of Corydalis saxicola total alkaloids in depression model rats

作　　者：叶峪 戴国梁[1] 杭华茜 于美双 王一然 邵雪文 居文政[1] YE Yu;DAI Guoliang;HANG Huaxi;YU Meishuang;WANG Yiran;SHAO Xuewen;JU Wenzheng(Dept.of Clinical Pharmacology,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临床药理科,南京210029

出　　处：《中国药房》2025年第1期30-36,共7页China Pharmacy

基　　金：江苏省中医药科技发展计划(No.MS2021011);江苏省基础研究计划(No.BK20211394);江苏省社会发展临床前沿技术项目(No.BE2023790)。

摘　　要：目的探讨冰片对岩黄连总碱在抑郁症模型大鼠中药效学和药动学的影响。方法将雄性SD大鼠30只按照随机数字表法分为空白对照组、阴性对照组、阳性对照组(灌胃氟西汀10 mg/kg)、单药组(灌胃岩黄连总碱210 mg/kg)、联合给药组(灌胃岩黄连总碱210 mg/kg+冰片50 mg/kg),每组6只。采用脂多糖(LPS)诱导造模,除空白对照组(未造模未给药)腹腔注射等量生理盐水外,其他各组大鼠每天腹腔注射1次LPS以建立抑郁症大鼠模型。造模1周后开始给药,各给药组按相应剂量灌胃药液,空白对照组及阴性对照组(不给予药物治疗)灌胃等体积溶解药物的溶剂,给药期间继续造模。连续给药2周后,通过行为学实验测试岩黄连总碱及岩黄连总碱与冰片联用对抑郁症模型大鼠抑郁样行为学的影响,测定大鼠血清中肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平,观察大鼠海马组织病理形态学变化。于第15天给药后不同时间点眼眶采血,取上层血浆,建立超高效液相色谱-三重四极杆串联质谱法同时测定单药组和联合给药组大鼠血浆中脱氢卡维丁、延胡索乙素、黄连碱、巴马汀、药根碱、小檗碱、小檗红碱和表小檗碱的分析方法,绘制血药浓度-时间曲线并计算曲线下面积(AUC),通过DAS 3.2.2软件对药动学参数进行分析。结果与空白对照组比较,阴性对照组大鼠体重、糖水偏好率降低,旷场运动总路程减少,游泳不动时间延长,血清中炎症因子表达升高(P<0.05);与阴性对照组比较,单药组和联合给药组大鼠糖水偏好率升高、旷场总路程延长、游泳不动时间缩短,血清中炎症因子表达降低(P<0.05);单药组和联合给药组大鼠以上指标无显著差异(P>0.05)。药动学结果显示,与单药组比较,联合给药组大鼠体内黄连碱AUC_(0-t),药根碱AUC_(0-t)、AUC_(0-∞)、t_(max)、c_(max),小檗红碱AUC_(0-t)、AUC_(0-∞)、t_(1/2)、c_(max),表小檗OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats.METHODS Thirty male SD rats were divided into blank control group,negative control group,positive control group(fluoxetine 10 mg/kg,i.g.),single drug group(C.saxicola total alkaloids 210 mg/kg,i.g.)and combined drug group(C.saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg,i.g.)according to the random number table method,with 6 rats in each group.By lipopolysaccharide(LPS)induction modeling,except blank control group(no model and no administration)received intraperitoneal injection of the same amount of normal saline,the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression.After 1 week of modeling,each administration group was given relevant drug intragastrically according to the corresponding dose,and blank control group and negative control group(without drug treatment)were administered intragastrically with an equal volume of solvent to dissolve the drug;continued modeling while administering the drug.After two weeks of continuous administration,the effects of C.saxicola total alkaloids versus the combination of C.saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments;the levels of tumor necrosis factor-α,interleukin-1βand interleukin-6 in rats were determined;the histopathological changes of the hippocampus of rats were observed.Blood sample was collected from the orbit at different time points after administration on the 15th day,and the upper plasma was obtained.Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine,tetrahydropalmatine,coptisine,palmatine,jatrorrhizine,berberine,berberrubine and epiberberine in rat plasma.The average plasma concentration-time curve was depicted,the area under the curve(AUC)was calculated,and the pharmac

关 键 词：岩黄连总碱 冰片 药物相互作用 药效学 药动学 抑郁 

分 类 号：R285.5[医药卫生—中药学] R969.2[医药卫生—中医学]