参归仁合剂对产后抑郁大鼠行为学及雌激素介导下ERK1/2通路中MEK1的影响

Effect of Shenguiren Mixture on Rats with Postpartum Depression Behavior and Impact of Estrogen Mediation on MEK1/ERK Signaling Pathways

目的:探讨参归仁合剂对产后抑郁模型大鼠行为学的影响,及测其海马、额叶、下丘脑神经元内胞外信号调节激酶1/2(ERK1/2)通路上丝裂原活化细胞外调节激酶1(MEK1)蛋白表达量。方法:150只雌性大鼠分为正常组,模型组,参归仁高、中、低剂量组(7,3.6,1.8 g·kg-1·d-1),阳性药组(舍曲林4.5 mg·kg-1·d-1和苯甲酸雌二醇0.01 mg·kg-1·d-1),除正常组外,其余各组ih苯甲酸雌二醇和黄体酮造成抑郁模型。观察其行为学指标变化;蛋白质免疫印迹(Western blot)法检测其额叶、海马、下丘脑中p-MEK1,MEK1的蛋白表达。结果:与正常组比较,模型组体重、食欲、活动能力、兴趣等明显降低,额叶、海马、下丘脑细胞内的p-MEK1蛋白表达显著升高(P<0.01);参归仁合剂能改善抑郁模型组体重、食欲、活动能力、兴趣等行为学指标,抑郁模型组额叶、海马、下丘脑细胞内的p-MEK1,MEK1蛋白表达量明显下降,参归仁高、中、低组额叶、海马、下丘脑细胞内的p-MEK1,MEK1蛋白表达量显著增加,尤其以参归仁中、低组增加较为明显(P<0.01)。结论:参归仁合剂能改善产后抑郁大鼠的行为学指标,在一定程度上调ERK1/2信号通路p-MEK1,MEK1的蛋白表达量,且中、低组效果显著,提示该药作用机制为调控ERK1/2通路并改善抑郁症状。

Objective： To study the effect of Shenguiren mixture on behavior of postpartum depression model rats,and measure protein expression of mitogen-activated extracellular regulated kinase 1（MEK1） on extracellular signal-regulated kinase 1/2（ERK1/2） channel in hippocampus,frontallobe and hypothalamus neurons. Method： Totally 150 female rats were divided into control group,model group,high,medium and lowdose Shenguiren groups（7,3. 6,1. 8 g·kg-1·d-1）,positive drug groups [sertraline group（4. 5 mg·kg-1·d-1）,and estradiol benzoate（0. 01 mg·kg-1·d-1） ]. Except for the normal group,all of the remaining groups were subcutaneously injected with estradiol benzoate and progesterone to establish the depression model. Changes in their behavioral indicators were observed. Protein expressions of p-MEK1,MEK1 in hippocampus,frontallobe,hypothalamus neurons were detected by Western blot. Result： Compared with normal group,model group showed significant decreases in weight,appetite,activity,interest,but increases in protein expression of p-MEK1 in hippocampus,frontallobe,hypothalamus neurons（P 0. 01）. Shenguiren mixture can improve behavioral indicators,such as weight,appetite,activity,interest of the postpartum depression model group. The depression model showed obvious decreases in protein expressions of p-MEK1,MEK1 in hippocampus,frontallobe,hypothalamus neurons. high,medium,low-dose Shenguiren groups showed obvious increases in protein expressions of p-MEK1,MEK1 in hippocampus,frontallobe,hypothalamus neurons,particularly in medium,low-dose Shenguiren groups. Conclusion： Shenguiren mixture can improve the behavioral indicators of the postpartum depression model rats,up-regulate protein expressions of p-MEK1,MEK1 of ERK1/2 signaling pathway to a certain extent,particularly in medium,low-dose Shenguiren groups. This suggests that the mechanism of Shenguiren mixture is to regulate ERK1/2 signaling pathway and alleviate symptoms of depression.