目的 探讨HPA轴紊乱致海马损伤与乳腺癌并发抑郁症（BCRD）的相关性。方法 将BALB/c雌性小鼠分为4组：对照组、乳腺癌组（腋下1次性接种0.1 mL的10⁷/mL 4T1炎性乳腺癌细胞）、抑郁症组（背部sc皮质酮混悬液30 mg/kg，每天1次，连续21 d）和BCRD（先进行乳腺癌造模后进行抑郁症造模）组，每组10只。每周1次糖水偏好测试；连续注射皮质酮21 d后，进行旷场、悬尾行为学实验；杀鼠取材，HE染色观察各组大鼠海马、肾上腺和肿瘤的病理改变；Elisa法检测血浆促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）、皮质酮含量。结果 与对照组比较，BCRD组小鼠糖水消耗明显降低（P<0.01），第3周与乳腺癌组比较显著下降（P<0.05）。与对照组、抑郁症组、乳腺癌组比较，BCRD组小鼠旷场实验中水平运动与垂直运动显著减少（P<0.05），悬尾实验中不动时间显著上升（P<0.01）。HE染色结果显示，与对照组比较，BCRD组小鼠海马、肾上腺出现明显病理改变，乳腺肿瘤细胞异常增生。与对照组比较，BCRD组血浆HPA轴相关指标皮质酮、ACTH和CRH含量显著升高（P<0.01、0.05）；与抑郁症组比较，BCRD组皮质酮、ACTH和CRH明显升高（P<0.05、0.01）；与乳腺癌组比较，BCRD组皮质酮、ACTH明显升高（P<0.05）。结论 BCRD小鼠存在快感缺乏、自主行为下降和绝望行为，并且海马和肾上腺存在明显损伤，HPA轴紊乱。

Objective To investigate the relationship between hippocampal injury induced by HPA axis disorder with breast cancer complicated with depression (BCRD). Methods A total of 40 BALB/c female mice were divided into four groups:blank group, simple breast cancer group (0.1 mL 10⁷/mL 4T1 inflammatory breast cancer cells were inoculated once on the axilla of mice), simple depression group (subcutaneous injection of 30 mg/kg corticosterone suspension was given on the back of mice, once daily for 21 d) and BCRD (establish depression model followed by breast cancer model establishment) group. The sugar water preference test was tested once a week; Detection open field experiment and tail suspension test were performed after continuous injection of corticosterone for 21 d in mice; HE staining was used to study the pathological changes of hippocampus, adrenal, and breast cancer tumors; Elisa was used to detect plasma adrenocorticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisone. Results Compared with control group, the consumption of sugar water in the BCRD group was significantly lower (P<0.01), and the consumption of sugar and water in BCRD group was significantly lower than that in breast cancer group at the 3rd week (P<0.05). The horizontal and vertical movements in the open field experiment were significantly decreased (P<0.05) compared with control group, depression group, and breast cancer group; The immobility time was significantly increased in the tail suspension test (P<0.01); HE staining showed that there were obvious pathological changes in the hippocampus and adrenal gland compared with control group; The CORT, ACTH, and CRH were increased significantly (P<0.05 and 0.01) compared with control group. Compared with depression group, corticosterone, ACTH, and CRH in BCRD group were increased significantly (P<0.05 and 0.01); Compared with breast cancer group, corticosterone and ACTH in BCRD group were increased significantly (P<0.05). Conclusion The BCRD mice had the characteristics of lack of pleasure, decreased autonomic behavior, and desperate behavior. Moreover, the hippocampus and adrenal gland of mice with HPA axis disorder were obviously damaged.

湖南省自然科学基金（2017JJ3235）；湖南省研究生创新项目（2017CX30）；湖南省研究生一方项目（YF201702）