Objective To explore the anti-depressive effects of Rosmarinic Acid ( RA) and its mechanisms on depressed rats with chronic unpredictable stress ( CUS) . Methods The rats were randomly divided into six groups ( n=16 for each group ): group A ( physiological saline ) , group B ( low-dose RA ) , group C ( high-dose RA ) , group D ( CUS + physiological saline) , group E ( CUS + low-dose RA) and group F ( CUS + high-dose RA) . After the inter-ventions, part of the established rat models ( n=8 for each group) underwent open-field and forced swimming tests, and then hippocampal tissue protein samples were taken out. Brain-derived neurotrophic factor ( BDNF) levels were detected by enzyme-linked immunosorbent assay ( ELISA ) , and levels of extracellular regulated protein kinase ( ERK1/2 ) and phosphorylation extracellular regulated protein kinase (pERK1/2) were detected by Western-blot method. The remaining animals ( n=8 for each group) underwent the Morris water maze ( MWM) test. Results The differences in results of e-thology test, ELISA detection for hippocampal tissue, albumen quantitations of pERK1/2 and ERK1/2 and retention per-centage of target quadrant in water maze experiment in group D were statistically significant (P<0. 05), and the differ-ences were also statistically significant between group F and D (P<0. 05), but there was no statistical significance be-tween group E with group D and F (P>0. 05), and the differences between group A, B and C showed no statistical sig-nificances (P>0. 05). Conclusion CUS rat models have depression-like behaviors, and RA can have an antidepres-sant-like effect. The antidepressant-like effect of RA may be achieved by increasing ERK1/2 phosphorylation level in hip-pocampus astroglia cells and improving BDNF releasing.%目的：探讨迷迭香酸( RA)对慢性不可预见应激( CUS)抑郁模型大鼠抑郁样行为的改善作用及机制。方法将大鼠随机分为6组,每组16只。 A组：生理盐水组；B组：低剂量RA组；C组：高剂量RA组；D组：CUS+生理盐水组；E组：CUS+低剂量RA组；F组：CUS+高剂量RA组。建立CUS抑郁大鼠模型,干预结束后对部分大鼠(每组8只)进行旷场实验、强迫游泳行为学测试后,取海马组织蛋白样品,酶联免疫吸附法( ELISA)检测脑源性神经营养因子(BDNF)水平,免疫印迹(Western-blot)法检测细胞外调节蛋白激酶(ERK1/2)、磷酸化细胞外调节蛋白激酶(pERK1/2)的蛋白表达水平。各组其余8只大鼠进行水迷宫实验。结果行为学实验、海马组织BDNF的ELISA检测、pERK1/2及ERK1/2蛋白定量及水迷宫实验目标象限停留时间百分比结果D组与A、B、C组比较均存在显著差异(P<0.05),F组与D组存在显著差异(P<0.05),而E组与D、F组之间无显著差异(P>0.05),A、B、C组之间差异也无统计学意义(P>0.05)。结论 CUS模型大鼠会表现出类似于抑郁症患者的抑郁样行为,而一定剂量的RA干预能改善这一行为,其机制可能为RA通过上调抑郁大鼠海马星形胶质细胞中ERK1/2的磷酸化,促进其释放BDNF,进而发挥抗抑郁效应。
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