丹参-川芎-红花对颅脑损伤后大鼠抑郁-心脏损伤的多病研究

A study of Danshen-Chuanxiong-Honghua on comorbidity of depression-heart injury in rats after traumatic brain injury

关键词:  颅脑损伤  即刻早期基因  胃饥饿素  神经营养因子  抑郁多病

Key words:  traumatic brain injury  c-Fos  Ghrelin  BDNF  comorbidity of depression

摘要:

[目的] 探究丹参-川芎-红花（丹川红，DCH）及主要吸收成分阿魏酸（FA）对颅脑损伤（TBI）模型大鼠抑郁-心脏损伤的治疗作用及多病发生机制研究。[方法] SD大鼠TBI造模，造模苏醒后给药，24 h后取材。分为空白（Sham）组，模型（Vehicle）组，FA（2 mg/kg）组、DCH（10 g/kg）组。用高尔基染色法检测海马神经元的树突棘密度和树突长度，酶联免疫吸附测定（ELISA）检测海马、心脏及血清中即刻早期基因（c-Fos）和胃饥饿素（Ghrelin）、心脏内皮型一氧化氮合成酶（eNOS）、血清五羟色胺（5-HT）和炎性因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）；蛋白免疫印迹法（Western blot）检测海马、心脏的脑源性神经营养因子（BDNF），心脏损伤指标肌酸激酶同工酶（CK-MB）和心肌凋亡指标半胺氨酸-天冬氨酸蛋白酶3（Caspase3）。[结果] TBI后大鼠海马神经元树突棘密度和长度均下降，治疗后有所恢复；血清炎性因子应激后明显上升，治疗后下降；5-HT应激后显著下降，治疗后上升。应激后显著下降的心脏eNOS水平治疗后升高，显著上升的心脏损伤指标CK-MB和Caspase3水平治疗后下降。c-Fos、Ghrelin在大鼠血清、海马、心脏中具有一致性的表达特征，前者在应激后表达量增高，给药后下降；后者在应激后表达量下降，给药后上升。BDNF在心脑中表现为应激后下降，给药后上升。[结论] TBI后大鼠具有抑郁-心脏损伤的多病表现，DCH和FA均发挥抗抑郁-心脏保护的作用，可能通过调节Ghrelin-BDNF/c-Fos这一共享途径对TBI后抑郁-心脏损伤共病发挥治疗作用。

Abstract:

[Objective] To explore the therapeutic effect and comorbidity mechanism of Danshen-Chuanxiong-Honghua and its main absorption component Ferulic acid on depression heart injury in traumatic brain injury（TBI） model rats. [Methods] SD rats were used to build traumatic brain injury model. After awakening，the model was treated with the medicine，and samples were taken after 24 h. Rats were divided into Sham group，Vehicle group，FA（2 mg/kg） group and DCH（10 g/kg） group. Using Golgi-Cox staining to measure the dendritic spine density and length in hippocampus neurons. Using ELISA to detect the c-Fos，Ghrelin in hippocampus，heart and serum，cardiac endothelial nitric oxide synthase（eNOS），Serum serotonin 5-HT，inflammatory factors interleukin IL-6，tumor necrosis factor TNF-α，Interleukin IL-β. Using Western blot to detect brain-derived neurotrophic factor BDNF expression in hippocampus and heart，cardiac injury index creatine kinase isoenzyme CK-MB and Myocardial apoptosis index Caspase3 expression in heart. [Results] After TBI，the length of hippocampal neurons and the density of dendritic spines decreased，inflammatory factors（IL-1β，IL-6 and TNF-α） in serum increased and 5-HT decreased. The level of eNOS in heart also decreased，the level of CK-MB and Caspase3 in heart increased. After treatment，the length of neurons in hippocampal increased，and the density of dendritic spines has a recovery trend. Inflammatory factors（IL-1β，IL-6 and TNF-α） in serum decreased，5-HT was increased. The level of eNOS in heart increased. CK-MB and Caspase3 in heart decreased. The expression levels of c-Fos and Ghrelin in the hippocampus，heart and serum have consistent expression characteristics. The expression level of the former increases after stress and decreases after treatment，the expression level of the latter decreased after stress and increased after treatment. BDNF appears to decrease after stress and increase after treatment in the heart and brain. [Conclusion] After TBI，rats exhibit depression-heart injury comorbidities. Both DCH and FA have antidepressant-cardioprotective effects and play a therapeutic role on the depression-heart injury comorbidities by regulating the shared pathway Ghrelin-BDNF/c-Fos.