氟西汀预处理对脑出血模型小鼠的影响研究  

Fluoxetine pre-treatment exacerbates bleeding in a mouse model of intracerebral hemorrhage

作　　者：郭婷婷 周杰[1] 郭建[1] GUO Tingting;ZHOU Jie;GUO Jian(Department of Neurology,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China;Department of Cardiology and Neurology,Chengfei Hospital,Chengdu,Sichuan 610091,P.R.China)

机构地区：[1]四川大学华西医院神经内科,成都610041 [2]成飞医院心内神内科,成都610091

出　　处：《华西医学》2022年第3期431-436,共6页West China Medical Journal

基　　金：国家自然科学基金(81971162)。

摘　　要：目的利用标化脑出血小鼠模型,确定氟西汀这种常见的选择性五羟色胺再摄取抑制剂类药物是否有加重出血可能。方法选择42只12~14个月龄无特定病原体级雌性C57BL/6小鼠。小鼠由简单随机法分为氟西汀组(氟西汀预处理)和对照组,各21只。氟西汀预处理7 d后,采用右侧纹状体胶原酶注射法构建小鼠脑出血模型。通过组织学、分子、细胞和行为学评估氟西汀对脑出血的作用。结果脑出血后第3天,对照组和氟西汀组出血体积分别为(4.59±1.80)mm^(3)和(6.09±1.08)mm^(3)。与对照组相比,氟西汀预处理明显加重了脑出血小鼠的神经功能缺损、脑出血体积、髓鞘损伤、血红蛋白及铁沉积、神经元变性和脑水肿(P<0.05)。尽管两组鼠尾出血时间比较差异无统计学意义,但氟西汀预处理有增加鼠尾出血时间的趋势[(276.73±211.06)vs.(438.00±236.79)s;t=-1.686,P=0.055]。结论氟西汀可能通过抑制血小板聚集进而加重脑出血。因此,严重脑出血合并抑郁症患者应适当避免联用该药。未来尚需更多的临床研究以验证这一结论。Objective To determine whether fluoxetine,a commonly used selective serotonin reuptake inhibitors(SSRIs),could exacerbate bleeding in a intracerebral hemorrhage(ICH)mouse model.Methods Forty two12-14 month old female specific pathogen free C57BL/6 mice were selected.Mice were randomly divided into fluoxetine group(fluoxetine pre-treatment)and control group,with 21 mice in each group.After treated with fluoxetine for 7 days,ICH was induced by injecting collagenaseⅦ-S into the right striatum of middle-aged female mice.Effects of fluoxetine on exacerbating bleeding were evaluated by a combination of histologic,molecular,cellular,and behavioral assessments.Results On the third day after ICH,the hemorrhage volumes of the control group and fluoxetine group were(4.59±1.80)mm^(3) and(6.09±1.08)mm^(3),respectively.In middle-aged female mice subjected to collagenase-induced ICH,fluoxetine pre-treatment significantly exacerbated neurological deficit,cerebral hemorrhage volume,myelin damage,hemoglobin and iron deposition,neuronal degeneration,and brain edema(P<0.05).Although there was no significant difference in tail bleeding time between the two groups,fluoxetine pre-treatment might increase tail bleeding time[(276.73±211.06)vs.(438.00±236.79)s;t=-1.686,P=0.055].Conclusions The use of fluoxetine and more generally of SSRIs,which inhibits platelet aggregation,may exacerbate bleeding after ICH.Thus,patients with depression after ICH may avoid concomitant use of such drugs when choosing an antidepressant.

关 键 词：氟西汀 脑出血 小鼠模型 选择性五羟色胺再摄取抑制剂 

分 类 号：R743.34[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]