基于IL-6/gp130信号研究逍遥抗癌解郁方调节乳腺癌并发抑郁症模型小鼠肿瘤、海马组织免疫的机制

Research Mechanism of Xiaoyao Kang’ai Jieyu Recipe in Regulating Tumor andHippocampus Immunity in Mice with Breast Cancer Complicated withDepression Based on IL-6/gp130 Signal

目的 观察逍遥抗癌解郁方(Xiaoyao Kang’ai Jiyu Formula,XYKAJY)对乳腺癌并发抑郁症(breast cancer related depression, BCRD)模型小鼠肿瘤、海马组织免疫的影响。方法 BALB/c雌性小鼠腋下接种1×106个/m L 4T1炎性乳腺癌细胞,7d后观察成瘤情况,将所有成瘤小鼠根据糖水偏好随机分为5组:模型组、紫杉醇合氟西汀组、逍遥抗癌解郁高剂量组、逍遥抗癌解郁低剂量组,并连续21 d背部皮下注射皮质酮(30 mg/kg)以复制BCRD模型,另设空白组。通过旷场、强迫游泳实验检测各组小鼠行为学变化;采用悬液芯片技术检测小鼠血清、海马、肿瘤、前额皮质中白细胞介素(interleukin, IL)-6的含量;采用免疫组化和Western blot法检测肿瘤、海马中白细胞介素6受体(interleukin 6 receptor, IL-6R)、糖蛋白130(glycoprotein 130, gp130)的蛋白表达。结果 与空白组比较,BCRD小鼠的水平及垂直活动次数降低(P<0.01),强迫游泳不动时间延长(P<0.01);血清、肿瘤、海马、前额皮质中IL-6的含量均显著升高(P<0.01,P<0.05);海马组织中IL-6R、gp130表达均显著升高(P<0.01,P<0.05)。与模型组比较,逍遥抗癌解郁高剂量能显著增加模型小鼠的水平及垂直活动次数(P<0.01,P<0.05),缩短游泳不动时间(P<0.01),降低血清、海马、前额皮质、乳腺肿瘤中IL-6含量(P<0.01或P<0.05),并有效降低肿瘤、海马组织中IL-6R、gp130表达(P<0.01,P<0.05)。结论 XYKAJY具有良好的抗癌解郁功效,其机制可能与IL-6/gp130信号异常紧密相关。

Objective To observe the effects of Xiaoyao Kang’ai Jiyu Formula(XYKAJY)on tumor and hippocampal immunity of breast cancer related depression(BCRD)model mice.Methods BALB/C female mice were inoculated with 1×106 cells/ml 4T1 inflammatory breast cancer cells in their armpits,and tumor formation was observed 7 days later.All the tumor-forming mice were randomly divided into 5 groups according to the sucrose preference:model group,paclitaxel combined with fluoxetine group,XYKAJY high-dose group,XYKAJY low-dose group,and subcutaneous injection of corticosterone(30 mg/kg)on the back for 21 consecutive days to replicate the BCRD model,and blank control group was also set.Behavioral changes of mice in each group were determined by open-field and forced swimming experiments.Suspension chip technology was used to detect the content of IL-6 in serum,hippocampus,tumor and prefrontal cortex.Immunohistochemistry and Western-blotting were used to detect the protein expression of IL-6R and gp130 in tumor and hippocampus.Results Compared with the blank group,the times of horizontal and vertical activities of BCRD mice were decreased(P<0.01),and the immobile time of forced swimming was prolonged(P<0.01).The levels of IL-6 in serum,tumor,hippocampus and prefrontal cortex were significantly increased(P<0.01,P<0.05).The expressions of IL-6R and gp130 in hippocampus were significantly increased(P<0.01,P<0.05).Compared with model group,XYKAJY high-dose could significantly increase the number of horizontal and vertical activities of model mice(P<0.01,P<0.05),shorten the immobile swimming time(P<0.01),and decrease the content of IL-6 in serum,hippocampus,prefrontal cortex and breast tumor(P<0.01,P<0.05).The expression of IL-6R and gp130 in tumor and hippocampus was decreased(P<0.01,P<0.05).Conclusion XYKAJY has a good anti-cancer and anti-depression effect,and its mechanism may be closely related to the abnormal IL-6/gp130 signal.