摘要
目的探讨舒郁胶囊抗抑郁的作用靶点及相关机制。方法 50只Wistar大鼠随机分为正常组、模型组、舒郁胶囊组、氟西汀组、WAY-100635组,每组10只,采用28天慢性温和应激制备抑郁症大鼠模型,造模期间舒郁胶囊组给予舒郁胶囊0.51 g/(kg·d)、氟西汀组给予氟西汀胶囊2×10-3g/(kg·d)、WAY-100635组给予WAY-100635 0.2×10-3g/(kg·d),正常组与模型组给予等量生理盐水灌胃。造模与干预前后分别记录各组大鼠体重,并观察各组大鼠旷场实验总分与糖水偏好系数。造模后各组选择6只大鼠采用蛋白质印迹法检测胃、肠组织中的5羟色胺1A受体(5-HTR1A)蛋白表达水平,环磷酸腺苷反应元件结合蛋白(CREB)磷酸化水平;采用ELISA法检测环磷酸腺苷(c AMP)含量变化。结果与正常组比较,模型组大鼠体重、旷场实验总分、糖水偏好系数均显著下降(P<0.01),而舒郁胶囊组与氟血汀组各指标均较正常组显著改善(P<0.05或P<0.01)。与正常组比较,模型组大鼠胃、肠组织中5-HTR1A蛋白相对表达量显著升高,c AMP含量和CREB磷酸化水平显著降低(P<0.05或P<0.01)。舒郁胶囊和WAY-100635可显著性降低大鼠胃、肠组织中5-HTR1A蛋白相对表达量,升高c AMP含量及CREB磷酸化水平(P<0.05或P<0.01);氟西汀可使大鼠胃、肠组织中c AMP含量及胃组织中CREB磷酸化水平显著升高(P<0.05或P<0.01)。结论舒郁胶囊可通过下调胃、肠组织中5-HTR1A蛋白表达,上调其下游信号通路中c AMP含量、CREB磷酸化水平发挥抗抑郁作用。
Objective To study the antidepressant functional target of Shuyu Capsule（ 舒郁胶囊） and its related mechanism. Methods Fifty Wistar rats were randomly divided into normal group,model group,Shuyu Capsule group,fluoxetine group and WAY-100635 group,10 in each. Depression model was made by 28-day chronic mild stress. During the modeling period,the Shuyu Capsule group was given Shuyu Capsule 0. 51 g /（ kg·d）,with the flu-oxetine group giving Fluoxetine Capsule 2 × 10- 3g /（ kg·d）,WAY-100635 group giving WAY-100635 0. 2 × 10- 3g /（ kg·d）,and equivalent normal saline was given to normal and model group. Body weight,open field test total score and the sucrose preference coefficient in each group were recorded before and after modeling and interventions. After modeling,6 rats in each group were picked to measure the expression of 5-hydroxytrytamine 1A receptor（ 5-HTR1A）and the phosphorylation level of c AMP response element binding（ CREB） in gastric and intestinal tissue by western blot,and the cyclic adenosine monophosphate（ c AMP） was detected by ELISA. Results Compared with normal group,the body weight,open field test total score and sucrose preference coefficient in model group decreased significantly（ P 0. 01）,meanwhile these indicators in Shuyu Capsule group and fluoxetine group were higher significantly（ P 0. 05 or P 0. 01）. Compared with normal group,much more 5-HTR1 A in gastric and intestinal tissue was expressed in model group,and much less c AMP and CREB phosphorylation was expressed（ P 0. 05 or P 0. 01）.Shuyu Capsule and WAY-100635 could remarkably lower the relative expression of 5-HTR1 A in murine gastric and intestinal tissue and improve c AMP and CREB phosphorylation（ P 0. 05 or P 0. 01）. Fluoxetine can upregulate the c AMP in murine gastric and intestinal tissue and enhance CREB phosphorylation in murine gastric tissue（ P 0. 05 or P 0. 01）. Conclusion Shuyu Capsule seems to perform the antidepressant function by down-regulating the expression of 5-HTR1 A in gastric and intestinal tissue as well as up-regulating c AMP and CREB phosphorylation in its downstream signaling pathway.
出处
《中医杂志》
CSCD
北大核心
2016年第21期1858-1863,共6页
Journal of Traditional Chinese Medicine
基金
国家自然科学基金(81072721)
