对药酸枣仁-合欢花对抑郁模型大鼠海马CA3区神经元凋亡GRP78蛋白表达的影响

目的研究对药酸枣仁-合欢花对抑郁模型大鼠海马CA3区神经元凋亡及葡萄糖调节蛋白78(GRP78)蛋白表达的影响,从内质网应激(ERS)角度探讨其抗抑郁作用机制。方法将雄性SD大鼠按随机数字表法分为正常对照组、模型组、对药酸枣仁-合欢花组、盐酸文拉法辛组;采用孤养加慢性不可预见性温和应激(CUMS)建立抑郁症大鼠模型,并用糖水消耗实验观察各组大鼠的行为学变化,用苏木素-伊红(HE)染色法观察海马CA3区神经细胞形态及数量。应用DNA原位末端缺口标记(TUNEL)法检测海马CA3区神经元凋亡情况,应用免疫组化法检测海马CA3区ERS通路的关键因子GRP78蛋白表达。结果与正常对照组比较,模型组大鼠糖水偏爱值下降(P <0.01),海马CA3区神经细胞数量减少(P <0.01)、凋亡细胞数和细胞凋亡率增加(P <0.01)、GRP78蛋白表达增加(P <0.01);与模型组比较,对药酸枣仁-合欢花组、盐酸文拉法辛组大鼠糖水偏爱值升高(P <0.05),海马CA3区神经细胞数量增加(P <0.05)、凋亡细胞数和细胞凋亡率降低(P <0.05或P <0.01)、GRP78蛋白表达增加(P <0.05)。结论对药酸枣仁-合欢花能显著改善抑郁模型大鼠的抑郁行为,具有抗抑郁功效,其机制可能与提高海马CA3区GRP78蛋白表达,抑制胱天蛋白酶-12(Caspase-12)表达,减缓ERS引起的细胞凋亡,维持内质网(ER)的稳定有关。

Effects of Herbal Pair Spinosae Ziziphi Semen and Albiziae Flos on Neuronal Apoptosis and GRP78 Protein Expression in Hippocampal CA3 Region of Depression Model Rats

Objective To study the effect of herbal pair spinosae Ziziphi semen and Albiziae flos on the neuronal apoptosis and the expression of GRP78 protein in the hippocampal CA3 area of the depression model rats,and to explore the antidepressant mechanism from the aspect of endoplasmic reticulum stress. Methods Male SD rats were divided into normal control group,model group,herbal pair spinosae Ziziphi semen and Albiziae flos group,and venlafaxine hydrochloride group by random number table. The depressive model rats was established by social isolation and chronic mild unpredictable stress (CUMS), and the behavioral changes of rats in each group were measured by sugar water consumption test;the morphology and quantity of neurons in the hippocampus CA3 region were observed after HE staining. Neuronal apoptosis in hippocampal CA3 region was detected by TUNEL,and the expression of GRP78 protein in the hippocampus CA3 region was detected by immunohistochemistry. Results Compared with the normal control group,the sugar water preference and number of neurons in the hippocampal CA3 region decreased (P < 0.01);the number of apoptotic cells and the apoptosis rate increased (P < 0.01),and the expression of GRP78 protein increased (P < 0.01) in the model group. Compared with the model group,the sugar water preference and number of neurons in the hippocampal CA3 region increased (P < 0.05);and the number of apoptotic cells and the apoptosis rate decreased (P < 0.05,P < 0.01),the expression of GRP78 protein increased (P < 0.05) in the herbal pair spinosae Ziziphi semen and Albiziae flos group and the venlafaxine hydrochloride group. Conclusion The herbal pair spinosae Ziziphi semen and Albiziae flos can significantly improve the symptoms of depressive model rats,and have antidepressant effect. The mechanism may be related to improving the expression of GRP78 protein in the CA3 region of the hippocampus, inhibiting Caspase- 12 expression, slowing apoptosis caused by ERS,and maintaining the stability of ER.