目的 探討HPA軸紊亂致海馬損傷與乳腺癌并發(fā)抑郁癥（BCRD）的相關(guān)性。方法 將BALB/c雌性小鼠分為4組：對照組、乳腺癌組（腋下1次性接種0.1 mL的10⁷/mL 4T1炎性乳腺癌細(xì)胞）、抑郁癥組（背部sc皮質(zhì)酮混懸液30 mg/kg，每天1次，連續(xù)21 d）和BCRD（先進(jìn)行乳腺癌造模后進(jìn)行抑郁癥造模）組，每組10只。每周1次糖水偏好測試；連續(xù)注射皮質(zhì)酮21 d后，進(jìn)行曠場、懸尾行為學(xué)實驗；殺鼠取材，HE染色觀察各組大鼠海馬、腎上腺和腫瘤的病理改變；Elisa法檢測血漿促腎上腺皮質(zhì)激素釋放激素（CRH）、促腎上腺皮質(zhì)激素（ACTH）、皮質(zhì)酮含量。結(jié)果 與對照組比較，BCRD組小鼠糖水消耗明顯降低（P<0.01），第3周與乳腺癌組比較顯著下降（P<0.05）。與對照組、抑郁癥組、乳腺癌組比較，BCRD組小鼠曠場實驗中水平運(yùn)動與垂直運(yùn)動顯著減少（P<0.05），懸尾實驗中不動時間顯著上升（P<0.01）。HE染色結(jié)果顯示，與對照組比較，BCRD組小鼠海馬、腎上腺出現(xiàn)明顯病理改變，乳腺腫瘤細(xì)胞異常增生。與對照組比較，BCRD組血漿HPA軸相關(guān)指標(biāo)皮質(zhì)酮、ACTH和CRH含量顯著升高（P<0.01、0.05）；與抑郁癥組比較，BCRD組皮質(zhì)酮、ACTH和CRH明顯升高（P<0.05、0.01）；與乳腺癌組比較，BCRD組皮質(zhì)酮、ACTH明顯升高（P<0.05）。結(jié)論 BCRD小鼠存在快感缺乏、自主行為下降和絕望行為，并且海馬和腎上腺存在明顯損傷，HPA軸紊亂。

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.

湖南省自然科學(xué)基金（2017JJ3235）；湖南省研究生創(chuàng)新項目（2017CX30）；湖南省研究生一方項目（YF201702）