3,6'-二芥子酰基蔗糖联合tenuifoliside A协同抗抑郁作用及其机制的研究  

Study on synergistic antidepressant effect of 3,6-disinapoyl sucrose combined with tenuifoliside A and its possible mechanism

作　　者：赵润清[1,2] 胡园[2] 李牧函 张静[2,4] 谭潇[2] 刘屏[2] 

机构地区：[1]河北北方学院药学院,河北张家口075000 [2]中国人民解放军总医院临床药理研究室,北京100853 [3]北京中医药大学中药学院,北京100853 [4]山西中医学院中药学院,山西太原030024

出　　处：《中国药理学通报》2016年第5期716-722,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81173579)

摘　　要：目的研究远志中3,6'-二芥子酰基蔗糖(DISS)和tenuifoliside A(TFSA)协同抗抑郁作用及其初步作用机制。方法采用经典的行为绝望抑郁模型——小鼠悬尾实验,随机分为对照组、阳性药组、DISS 5、10 mg·kg^(-1)、TFSA 5、10mg·kg^(-1)、DISS 5 mg·kg^(-1)+TFSA 5 mg·kg^(-1)、DISS 5 mg·kg^(-1)+TFSA 10 mg·kg^(-1)、DISS 10 mg·kg^(-1)+TFSA 5 mg·kg^(-1)和DISS 10 mg·kg^(-1)+TFSA 10 mg·kg^(-1);灌胃给药7 d,观察DISS和TFSA单体及其合用对小鼠悬尾不动时间的影响;免疫组织化学方法检测小鼠海马及皮层内BDNF的表达;蛋白质印记法检测小鼠海马内CRTC1、CREB、p-CREB及BDNF的表达。结果 DISS和TFSA及其二者合用均可缩短悬尾小鼠的不动时间,其中DISS(10 mg·kg^(-1))和TFSA(10 mg·kg^(-1))组与单剂量药物组相比明显,并稳定缩短小鼠悬尾不动时间(P<0.05)。免疫组化实验中,DISS和TFSA及其合用组均可提高海马及皮层内BDNF的表达量(P<0.05),同时DISS和TFSA及其合用组可增加海马中CRTC1、CREB、p-CREB及BDNF蛋白的含量,其中合用组明显高于单药组(P<0.05)。结论 DISS与TFSA双药合用启动CREB共转录因子CRTC1,激活海马内CREB的磷酸化,进而增加其下游BDNF表达,发挥协同抗抑郁作用。Aim To study the synergistic anti-depres-sion effect of 3 , 6-disinapoyl sucrose ( DISS ) and&nbsp;tenuifoliside A ( TFSA ) from Radix Polygalae and the preliminary mechanism . Methods Using the classical&nbsp;behavioral despair and depression model of mouse tail suspension test, 120 mice were divided into control group, positive group, DISS 5 mg·kg-1 group,DISS 10 mg·kg-1 group,TFSA 5 mg·kg-1 group,TFSA 10 mg· kg-1 group, DISS 5 mg · kg-1 +TFSA 5 mg · kg-1 group,DISS 5 mg·kg-1 +TFSA 10 mg·kg-1 group,DISS 10 mg·kg-1 +TFSA 5 mg·kg-1 group and DISS 10 mg · kg-1 +TFSA 10 mg · kg-1 group randomly. They were given intragastric injection for 7 days continuously, to observe the effect of DISS and TFSA monomer and its combination on the time of mouse tail suspension. Expression of BDNF in the hip-pocampus of mice was detected by immunohistochemis-try. The expressions of CREB, pCREB, CRTC1 and BDNF in the hippocampus of mice were detected by Western blot method. Results The administration of DISS and TFSA could shorten the immobility time of&nbsp;mice subjected to the tail. DISS ( 10 mg · kg-1 ) and TFSA( 10 mg · kg-1 ) group were significantly lower than single dose drug group(P<0. 05). DISS and TF-SA and the combination groups could increase the ex-pression of BDNF in hippocampus and cortex by immu-nohistochemistry(P <0. 05). At the same time, the contents of CREB, CRTC1, pCREB and BDNF protein in the hippocampus were increased by DISS and TF-SA, and the combination group was significantly higher than the single drug group ( P<0. 05 ) . Conclusion The administration of DISS and TFSA are used to acti-vate CREB transcription factor CRTC1 , and activate the phosphorylation of CREB in the hippocampus, and then increase the expression of BDNF in the hippocam-pus and plays a synergistic antidepressant effect.

关 键 词：DISS TFSA 抑郁症 协同作用 CREB BDNF 

分 类 号：R-332[医药卫生] R284.1