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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。
Objective: This study was designed to investigate the protective effects of different doses of Tamoxifen on brain injury in early experimental cerebral hemorrhage (ICH) rats. Methods: Fifty-six male Sprague-Dawley rats were injected with 100 μL autologous arterial blood into the right basal ganglia to make ICH model and divided into 3 groups. The brain water content and pathological observation group (n = 6 in all subgroups) at 24 hours after ICH were given different doses of Tam (Tam 2.5 mg · kg -1) and Tam 5 mg · kg -1 -1) group and 4% DMSO normal saline (24 h control group) were injected intraperitoneally. After 24 h, the brain water content and pathological changes were observed. (2) After 72 hours of ICH, rats in observation group (n = 6 in each subgroup) received different doses of Tam (72 h at 2.5 mg · kg -1 and 2.5 mg · kg -1 at 2 h and 24 h after ICH, 1) group, 72hTam 2.5mg.kg -1 +5 mg · kg -1 group, 72h Tam 5mg.kg -1 +5 mg · kg -1 group) and 4% DMSO Normal saline (72 h control group) was intraperitoneally injected, and the brain water content was measured at 72 h postoperatively. ③28 d imaging and pathological observation group: rats were given tam (28d Tam 5mg.kg -1 +5mg, kg -1) twice a day after ICH (n = 6) , 4% DMSO normal saline (28 d control group) (n = 8) were injected intraperitoneally, followed by MRI and behavioral changes at 1, 7, 14 and 28 days postoperatively, and sacrificed on the 28th day for histological examination. Results: Tam5 mg · kg ~ (-1) significantly reduced cerebral edema (P <0.05) 3 d after ICH and improved postoperative behavioral score (P <0.05), and significantly reduced the ipsilateral Cerebral atrophy of the caudate nucleus (P <0.01), but MRI showed an abnormal enlargement of supratentorial ventricles in 2 rats. CONCLUSION: Tam, a selective estrogen receptor modulator, has obvious neuroprotective effect after ICH, but adverse reactions of hydrocephalus occur and need further study.