酸枣仁和合欢花水提取物对焦虑性抑郁症模型大鼠HPA轴 及炎症因子的影响

目的：探讨酸枣仁和合欢花水提取物对焦虑性抑郁症模型大鼠下丘脑-垂体-肾上腺（HPA）轴及炎症因子的作用，阐明其配伍应用的效果及其作用机制。方法：80只Wistar大鼠随机分为对照组、模型组、低剂量酸枣仁组、高剂量酸枣仁组、低剂量合欢花组、高剂量合欢花组、低剂量酸枣仁-合欢花组和高剂量酸枣仁-合欢花组，每组10只。采用应激束缚+孤笼饲养，并联合皮质酮（CORT）皮下注射的方法复制焦虑性抑郁症大鼠模型。强迫游泳实验（FST）观察各组大鼠强迫游泳静止时间；高架十字迷宫实验（EPM）观察各组大鼠进入开放臂的次数（OE）、进入封闭臂的次数（CE）、进入开放臂的时间（OT）和进入封闭臂的时间（CT），并计算进入开放臂和封闭臂的总次数（TE）和OE％及OT％。ELISA法检测各组大鼠血清中促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）、CORT和炎症因子白细胞介素1β（IL-1β）及白细胞介素6（IL-6）水平；HE染色检测各组大鼠海马神经细胞形态表现。结果：与模型组比较，低和高剂量酸枣仁-合欢花组、高剂量酸枣仁组及高剂量合欢花组大鼠强迫游泳静止时间明显缩短（P<0.05或P<0.01）；与低剂量酸枣仁-合欢花组比较，低剂量酸枣仁组和低剂量合欢花组大鼠强迫游泳静止时间明显延长（P<0.05或P<0.01）；与高剂量酸枣仁组和高剂量合欢花组比较，高剂量酸枣仁-合欢花组大鼠强迫游泳静止时间明显缩短（P<0.01）。与模型组比较，低和高剂量酸枣仁-合欢花组、高剂量酸枣仁组及高剂量合欢花组大鼠OE%和OT%明显升高（P<0.05或P<0.01）；与低剂量酸枣仁组和低剂量合欢花组比较，低剂量酸枣仁-合欢花组大鼠OE%和OT%明显升高（P<0.05或P<0.01）；与高剂量酸枣仁组和高剂量合欢花组比较，高剂量酸枣仁-合欢花组大鼠OE%和OT%明显升高（P<0.05或P<0.01）。与模型组比较，低和高剂量酸枣仁-合欢花组、高剂量酸枣仁组及高剂量合欢花组大鼠血清中CHR、ACTH、CORT、IL-1β和IL-6水平明显降低（P<0.05或P<0.01）；与低剂量酸枣仁组和低剂量合欢花组比较，低剂量酸枣仁-合欢花组大鼠血清中CHR、ACTH、CORT、IL-1β和IL-6水平均明显降低（P<0.05或P<0.01）；与高剂量酸枣仁组和高剂量合欢花组比较，高剂量酸枣仁-合欢花组大鼠血清中CHR、ACTH、CORT、IL-1β及IL-6水平均明显降低（P<0.05或P<0.01）。HE染色，模型组大鼠海马神经细胞排列松散，大量神经细胞变性，细胞层次减少；低和高剂量酸枣仁-合欢花组大鼠海马神经细胞变性明显缓解，神经细胞排列紧密、细胞层次清晰。结论：酸枣仁与合欢花配伍应用能够改善焦虑性抑郁症大鼠的行为，保护大鼠海马神经元，降低焦虑性抑郁症大鼠炎症反应水平及调节HPA轴紊乱。

Effect of water extract of spina date seed and albizzia julibrissin flower on hpa axis and inflammatory cytokines in anxious depression model rats

Objective:To investigate the effects of spina date seed (SDS)and albizzia julibrissin flower(AJF) water extracts on the hypothalamic-pituitary-adrenal (HPA) axis and inflammatory factors(IF) in the anxiety depression model rats. Methods:A total of 80 Wistar rats were randomly divided into blank group(n=10),model group(n=10), low dose of SDS group(n=10),high dose of SDS group(n=10), low dose of AJF group(n=10),high dose of AJF group(n=10),low dose of SDS-AJF group(n=10),and high dose of SDS-AJF group(n=10).The rat models of anxiety depression were induced by chronic restraint stress,solitary cage and corticosterone(CORT) subcutaneous injection.The forced swimming test (FST) was used to observe the immobility time of forced swimming of the rats in various groups;Elevated plus maze test (EPM) was used to observe the open arm entry(OE),close arm entry(CE),open arm entry time(OT), and close arm entry time(CT) of the rats in various groups.The total entry of open arms and close arms(TE),OE% and OT% were calculated.ELISA method was used to detect the levels of serum corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH),CORT,inflammatory factors interleukin-1β(IL-β) and interleukin-6 (IL-6) of the rats in various groups.HE staining was used to observe the morphology of hippocampal neurons of the rats in various groups. Results:Compared with model group,the immobility time of forced swimming of the rats in low dose of SDS-AJF group,high dose of SDS-AJF group,high dose of SDS group and high dose of AJF group was decreased (P<0.05 or P<0.01);compared with low dose of SDS group and low dose of AJF group, the immobility time of forced swimming of the rats in low dose of SDS-AJF group was shortened (P<0.05 or P<0.01);compared with high dose of SDS group and high dose of AJF group,the immobility time of forced swimming of the rats in high dose of SDS-AJF group was shortened(P<0.05 or P<0.01). Compared with model group,the OE% and OT% of the rats in low dose of SDS-AJF group,high dose of SDS-AJF group,high dose of SDS group and high dose of AJF group were increased (P<0.05 or P<0.01);compared with low dose of SDS group and low dose of AJF group,the OE% and OT% of the rats in low dose of SDS-AJF group were increased(P<0.05 or P<0.01);compared with high dose of SDS group and high dose of AJF group,the OE% and OT% of the rats in high dose of SDS-AJF group were increased (P<0.05 or P<0.01).Compared with model group,the levels of serum CRH, ACTH, CORT, IL-1β, and IL-6 of the rats in low dose of SDS-AJF group,high dose of SDS-AJF group,high dose of SDS group and high dose of AJF group were decreased(P<0.05 or P<0.01);compared with low dose of SDS group and low dose of AJF group,the levels of serum CRH, ACTH, CORT, IL-1β and IL-6 of the rats in low dose of SDS-AJF group was decreased(P<0.05 or P<0.01);compared with high dose of SDS group and high dose of AJF group,the levels of serum CRH, ACTH, CORT, IL-1β, and IL-6 of the rats in high dose of SDS-AJF group was decreased(P<0.05 or P<0.01).The HE staining results showed that the hippocampal neurons of the rats in model group were loosely arranged, and a large number of nerve cells were degenerated and the cell layer was reduced. The degeneration of hippocampal neurons of the rats in low and high doses of SDS-AJF groups were significantly relieved, and the nerve cells were arranged closely and the cell layer was clear. Conclusion:Combination of SDS and AJF can improve the behavior of the rats with anxiety depression,protect the hippocampal neurons of rats, reduce the inflammatory response, and adjust the disorder of HPA axis.