逍遥抗癌解郁方对乳腺癌并发抑郁症小鼠海马神经元突触后致密蛋白95表达的影响

Effect of Xiaoyao Kang’ai Jieyu Prescription on Hippocampal Neuron Postsynaptic Density Protein 95 Expression in Mice with Breast Cancer Related Depression

目的观察逍遥抗癌解郁方对乳腺癌并发抑郁症(BCRD)小鼠海马神经元突触后致密蛋白95(PSD95)的影响,探讨其对海马组织的可能保护机制。方法腋下注射4T1炎性乳腺癌细胞联合背部皮下注射皮质酮建立BCRD小鼠模型。随机分为模型组、紫杉醇组、紫杉醇+氟西汀组、逍遥抗癌解郁方组、紫杉醇+逍遥抗癌解郁方组,另取未造模BALB/c小鼠作为正常组。采用悬尾实验和强迫游泳实验检测小鼠抑郁样行为,HE染色观察小鼠海马和乳腺肿瘤病理变化,免疫组化染色和Western blot检测小鼠海马PSD95的表达。结果与正常组比较,模型组小鼠悬尾实验、强迫游泳实验不动时间显著增加(P<0.01),海马结构损伤明显,PSD95表达水平显著降低(P<0.01);给予逍遥抗癌解郁方干预后,模型小鼠悬尾实验、强迫游泳实验不动时间明显减少(P<0.05),海马结构损伤得以恢复,PSD95表达显著升高(P<0.01),联合紫杉醇出现肿瘤细胞大面积坏死。结论逍遥抗癌解郁方可改善BCRD小鼠抑郁症状,有效辅助化疗药物抑制乳腺肿瘤增殖,并通过上调突触可塑性相关蛋白PSD95的表达,保护海马组织。

Objective To study the effect of regulation of Xiaoyao Kang’ai Jieyu Prescription on hippocampal neuron postsynaptic density protein 95(PSD95)in mice with breast cancer related depression,and to elucidate its possible mechanism of protect hippocampus.Methods The BCRD mice model was established by axillary injection of 4T1 inflammatory breast cancer cells combined with subcutaneous injection of corticosterone in the back and randomly divided into model group,paclitaxel group,paclitaxel+fluoxetine group,Xiaoyao Kang’ai Jieyu Prescription group,paclitaxel+Xiaoyao Kang’ai Jieyu Prescription group.Another unmodeled BALB/c mice were taken as the normal group.Detection of depression-like behavior in mice with tail suspension test and forced swimming test.The pathological structurre changes of hippocampus and breast tumors were observed by HE staining. The expression of PSD95 in hippocampus of mice was detected by immunohistochemical staining andWestern blot. Results Compared with the normal group, the immobility time in the tail suspension test and forcedswimming test of the model group significantly increased (P<0.01), the hippocampal formation was significantlydamaged, and the expression level of PSD95 significantly decreased (P<0.01). After the intervention of XiaoyaoKang’ai Jieyu Prescription, the immobility time of the model mice obviously reduced in the tail suspension test andforced swimming test (P<0.05), the hippocampal structural damage was restored, and the expression level of PSD95significantly increased (P<0.01). Combined with paclitaxel, large areas of tumor cell necrosis could be observed.Conclusion Xiaoyao Kang’ai Jieyu Prescription can improve the depressive symptoms of BCRD mice, effectivelyassist chemotherapy drugs to inhibit breast tumor proliferation, and protect hippocampus by up-regulating theexpression of synaptic plasticity related protein PSD95.