摘要
目的:研究体外培育牛黄(CBS)联合氟哌啶醇对精神分裂症模型大鼠行为学的影响并探索其作用机制。方法:以地卓西平马来酸盐(MK-801)制备大鼠精神分裂症模型。SD大鼠随机分为对照组,模型组,氟哌啶醇组(1.4 mg·kg-1),氟哌啶醇联合CBS低剂量(50 mg·kg-1)、中剂量(100 mg·kg-1)、高剂量(150 mg·kg-1)组,CBS低剂量(50 mg·kg-1)、中剂量(100 mg·kg-1)、高剂量(150 mg·kg-1)组。用高架十字实验评价各组大鼠焦虑水平的影响,Western blot检测各组大鼠前额皮层c-Fos蛋白水平。结果:高架十字实验结果显示,氟哌啶醇组和联合用药组大鼠开臂次数百分比相比模型组明显增加(P<0.01),而CBS各剂量组与模型组无显著差异。联合用药中、高剂量组开臂时间百分比显著大于氟哌啶醇组(P<0.05)。CBS和氟哌啶醇均可降低大脑前额皮层中c-Fos蛋白含量(P<0.05或P<0.01);而联合用药各剂量组较氟哌啶醇组c-Fos蛋白含量均显著降低(P<0.05)。结论:通过行为学评价发现,CBS与氟哌啶醇联合使用能协同降低大鼠精神分裂症模型中增高的焦虑水平,这可能与协同降低前额皮层c-Fos蛋白含量有关。本研究为临床上两药的联合使用提供了药效学基础,具有一定的参考意义。
Objective： To investigate the synergetic anti-schizophrenia effects in rats using Calculus Bovis Sativus（ CBS） in the combination with haloperidol,and explore the underlying mechanisms of action. Methods： Rats were randomly arranged： control,model,haloperidol alone（ 1. 4 mg/kg）,haloperidol combined with 50 mg/kg,100 mg/kg,150 mg/kg CBS,50 mg/kg,100 mg/kg,150 mg/kg CBS. Elevated plus maze test was conducted to verify the pharmacodynamic effects of a combination treatment of CBS and haloperidol on MK-801-induced schizophrenic rats. After anxiety level was evaluated,content of c-Fos in prefrontal cortex of cerebral tissues were also evaluated. Results： The elevated plus maze test data displayed a significantly increase（ P〈0. 01） in the percentage of open arm entries in haloperidol group and haloperidol combined with CBS groups than model group,but CBS groups did not show significant change. And the percentage of open arm time significantly increased when haloperidol was concomitantly administered with 100 mg/kg and 150 mg/kg CBS compared with haloperidol administration alone（ P〈0. 05）. CBS and haloperidol significantly decreased the content of c-Fos in prefrontal cortex of cerebral tissues compared to model group（ P〈0. 05 or P〈0. 01）. Levels of c-Fos were reduced in haloperidol combined with CBS groups compared with haloperidol alone（ P〈0. 05）. Conclusion： The experimental results suggested that oral co-administration of CBS with HAL resulted in a synergistic effect in rats. The findings of this study provide the basis of pharmacodynamics for the combination use of the two medicines,which exhibits great practical reference value.
作者
贺国芳
雷凯
李娟
张思
刘雅楠
杨金玉
刘东
He Guofang;Lei Kai;Li Juan;Zhang Si;Liu Ya＇ nan;Yang Jinyu;Liu Dong(Department of Pharmacy of Tongji Hospital,Tongji Med-ical School,Huazhong Science and Technology University,Wuhan 430030,Chin)
出处
《中国药师》
CAS
2018年第8期1335-1339,共5页
China Pharmacist
基金
湖北省自然科学基金面上项目(编号:2016CFB628)
