雌激素对脑卒中后抑郁大鼠海马和杏仁核脑源性生长因子-磷酸化酪氨酸激酶B表达以及行为学的影响

Effects of Estrogen on Depressive-like Behavior and Expression of Brain-derived Neurotrophic Factor and Phosphorylation Tyrosine Kinase B in Hippocampus and Amygdala in Spontaneous Post-stroke Depression Rat

目的通过观察雌激素对缺血性脑卒中后抑郁大鼠模型海马和杏仁核的脑源性生长因子(BDNF)-磷酸化酪氨酸激酶B(pTrkB)的表达,探讨缺血性脑卒中后内源性抑郁的发病机制。方法将SD雌性大鼠随机分为对照组12只(无任何干预)、模型组16只(MCAO术后2周,皮下注射大豆油,持续2周)和雌激素组16只(MCAO术后2周,皮下注射溶有10μg 17β-雌二醇的0.1 mL大豆油,持续2周)。通过旷场实验和强迫游泳实验观察大鼠行为学变化,应用免疫组化和Western blot方法观察海马和杏仁核中BDNF和pTrkB表达。结果雌激素干预后:①旷场实验和强迫游泳中,大鼠行为学评分均显著提高,雌激素组与模型组比较,差异有统计学意义(P<0.01);②免疫组化法观察示雌激素组海马和杏仁核BDNF阳性细胞数与模型组比较明显增多,差异有统计学意义(P<0.05);③Western blot法检测示雌激素组BDNF/β-actin和pTrkB/TrkB灰度比值较模型组明显提高(P<0.05)。结论雌激素能改善脑卒中后大鼠的抑郁行为,其机制可能是通过BDNF-pTrkB信号通路的变化而改善PSD症状。

Aim To explore the effect of estrogen on brain-derived neurotrophic factor （BDNF）, and its receptor tyrosine kinase B （TrkB） and phosphorylation tyrosine kinase B （pTrkB） expression in hippocampus and amygdala of post-stroke depression （PSD） rats. Methods Female Sprague-Dawley rats were randomly divided into a control group, a PSD group and an estrogen group. The PSD rats in the estrogen group were injected subcutaneously with 10 μg 17β-estradiol for 2 weeks. All animals were assessed for depression-like behavior at a specific time. The expression ofBDNF, pTrkB and TrkB in the hippocampus and amygdala were investigated using immunohistochemistry and Western blot. Results The scores of PSD group had a significant decrease either in crossing activity or in frequency of rearing compared with the control group （P〈0.01）, and Estrogen administration showed a increase in frequency of crossing activity and rearing activity compared with PSD group （P〈0.01）. Compared with the control group, the immobility time of PSD group was longer（P〈0.01）. Estrogen group showed a significant decrease in the immobility time compared with PSD group （P〈0.01）. A significant regulation of BDNF/[3-actin and pTrkB/TrkB ratio in hippocampus and amygdala were observed in PSD animals treated with estradiol, compared with treated with oil （P〈0.01）. Likewise, Estrogen can increase the protein level of BDNF and pTrkB in amygdala compared with PSD group （P〈0.05）. Conclusion Estrogen treatment may improve depression-like behavior in PSD rats by modulating the BDNF-pTrkB signaling pathway.