返回 
加入收藏
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
x
请在关注微信后，向客服人员索取文件
| 篇名： | 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 |
| TITLE： | Effects of borneol on pharmacodynamics and pharmacokinetics of Corydalis saxicola total alkaloids in depression model rats |
| 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10mg/kg）、单药组（灌胃岩黄连总碱210mg/kg）、联合给药组（灌胃岩黄连总碱210mg/kg+冰片50mg/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DAS3.2.2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AUC0-t，药根碱AUC0-t、AUC0-∞、tmax、cmax，小檗红碱AUC0-t、AUC0-∞、t1/2、cmax，表小檗碱AUC0-t，脱氢卡维汀cmax，巴马汀cmax均显著升高（P＜0.05）。结论岩黄连总碱单用及与冰片联用均能改善抑郁症模型大鼠抑郁样行为，减轻血清炎症因子水平，保护海马神经元。与岩黄连总碱单用相比，与冰片联用虽未表现出明显的药效学差异，但能提高模型大鼠体内黄连碱、药根碱等的吸收。 |
| ABSTRACT： | 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-1β and 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 pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group， the negative control group had a decrease in body mass and sugar water preference rate， a decrease in the total distance of open field， a prolonged swimming immobility time， and a increased in the expression of inflammatory factors in serum （P＜0.05）； compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water， increased the total distance of open field， shortened the time of swimming immobility， and decreased the expression of inflammatory factors in serum （P＜0.05）. There was no significant difference in the above indicators between the single drug group and the combined drug group in rats （P＞0.05）. Pharmacokinetic results showed that compared with single drug group， AUC0-t of coptisine， AUC0-t， AUC0-∞， tmax and cmax of jatrorrhizine， AUC0-t， AUC0-∞， t1/2 and cmax of berberrubine， and AUC0-t of epiberberine， cmax of dehydrocarvedine， cmax of palmatine were significantly increased in combined drug group， but there was no significant difference， indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats， reduce serum inflammatory cytokine levels， and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone， the combination with borneol do not show significant pharmacodynamic differences， bu can improve the absorption of coptisine， jatrorrhizine in model rats. |
| 期刊： | 2025年第36卷第01期 |
| 作者： | 叶峪；戴国梁；杭华茜；于美双；王一然；邵雪文；居文政 |
| AUTHORS： | YE Yu，DAI Guoliang，HANG Huaxi，YU Meishuang，WANG Yiran，SHAO Xuewen，JU Wenzheng |
| 关键字： | 岩黄连总碱；冰片；药物相互作用；药效学；药动学；抑郁 |
| KEYWORDS： | Corydalis saxicola total alkaloids； borneol； drug interactions； pharmacodynamics； pharmacokinetics； depression |
| 阅读数： | 6 次 |
| 本月下载数： | 0 次 |
* 注：未经本站明确许可，任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作！
