大鼠脑出血早期应用他莫西芬的治疗作用  

Different Doses of Early Tamoxifen Treatment for Intracerebral Hemorrhage in Rats

作　　者：谢清[1,2,3] 叶子[4] 宫晔[1,2,3] 陈衔城[1,2,3] 黄峰平[1,2,3] 奚国华[1,5] 华亚[1,5] 

机构地区：[1]复旦大学附属华山医院神经外科,200040 [2]上海市神经外科临床医学中心,200040 [3]复旦大学上海医学院神经外科学系,200032 [4]复旦大学附属华山医院心内科,200040 [5]美国密歇根大学神经外科,美国48109

出　　处：《中国临床神经科学》2012年第5期481-487,共7页Chinese Journal of Clinical Neurosciences

基　　金：国家自然科学基金面上项目(编号:30872675);青年项目(编号:30901549)

摘　　要：目的:本研究探讨大鼠实验性脑出血(ICH)早期应用不同剂量他莫西芬(Tam)对脑损伤的保护作用。方法:雄性SD大鼠56只,予右侧基底节注射100μL自体动脉血制作ICH模型,并分为3大组。①24h脑水含量及病理观察组(各亚组均n=6):大鼠在ICH后2 h分别接受不同剂量Tam(Tam 2.5 mg·kg^(-1)组、Tam 5 mg·kg^(-1)组)和4%DMSO生理盐水(24 h对照组)腹腔注射,24 h后处死进行脑水含量及病理观察。②72 h脑水含量观察组(各亚组均n=6):大鼠在ICH后2h和24h分别接受不同剂量Tam(72h Tam2.5mg·kg^(-1)+2.5mg·kg^(-1)组、72hTam2.5mg.kg^(-1)+5mg·kg^(-1)组、72h Tam 5mg.kg^(-1)+5mg·kg^(-1)组)和4%DMSO生理盐水(72 h对照组)腹腔注射,于术后72 h处死测量脑水含量。③28 d影像学及病理学观察组:大鼠在ICH后2和24h分别2次给予tam(28d Tam 5mg.kg^(-1)+5mg,kg^(-1)组)(n=6),4%DMSO生理盐水(28 d对照组)(n=8)腹腔注射,分别在术后1、7、14和28d随访MRI和行为学变化,并在第28天处死进行组织学检查。结果:Tam5 mg·kg^(-1)能明显减轻ICH后3 d时脑水肿(P<0.05),改善术后行为学评分(P<0.05),并能明显减轻ICH术后28 d同侧尾状核的脑萎缩(P<0.01),但MRI提示2例大鼠出现幕上脑室异常扩大。结论:Tam作为选择性雌激素受体调节剂,在ICH后有明显的神经保护作用,但发生了脑积水的不良反应,需要进一步的研究。To study the effects of different doses oftamoxifen on reducing experimental intracerebral hemorrhage （ICH）-induced brain injury in rats early treatment. Methods： 56 adult male SD rats received an injection of 100 μL autologous whole blood into the right basal ganglia and were divided into 3 groups. ① 24 hour-measured group： rats were treated with different doses of tamoxifen 2 hours after ICH and were killedafter 24 hours to be measured brain water content. There were Tam 2.5 mg·kg^-1, Tam 5 mg·kg^-1 and 4% DMSO saline subgroups （n=6 in each subgroup）. ② 72 hour-measured group： rats were treated with different doses of tamoxifen at 2 and 24 hours twice after ICH, and were killed at 72 hours to be measured brain water content. There were Tam 2.5 mg.kgl＋2.5 mg·kg^-1 group, Tam 2.5 mg·kg^-1＋5 mg·kg^-1 group, Tam 5 mg·kg^-1＋5 mg·kg^-1 group and 4% DMSO saline subgroup （n=6 in each subgroup）. ③28 day-measured group： rats were treated with tamoxifen （5 mg·kg^-1,i.p.） at 2 and 24 hours twice after ICH. Magnetic resonance imaging （MRI） and behavior tests were examined at ICH. Then the rats were killed at 28 days and the brain histological examinations were made. There were Tam 5 mg·kg^-1＋5 mg·kg^-1 subgroup and 4% DMSO saline subgroup （n=6 in each subgroup）. Results： Only two injections of 5 mg·kg^-1 tamoxifen dose at 2 hours and 24 hours after ICH could reduce perihematomal brain edema at 3 days（P〈0.05）. Tamoxifen could also reduce ipsi-lateral caudate atrophy at 28 days for histology examination （P〈0.01）. And neurological deficits outcome was better in tamoxifen treated group （P〈0.05）. MRI demonstrated smaller T2^＊ lesions in tamoxifen-treated rats. But there were 2 rats developed abnormal ventricle dilation on MRI follow-up. Conclusion： The results suggested that tamoxifen could have obvious neuroprotective effects in ICH at a certain dosage, and the side effect of onset of hydrocephalus was suspected.

关 键 词：脑出血 脑水肿 脑萎缩 脑积水 他莫西芬 

分 类 号：R742[医药卫生—神经病学与精神病学]