他莫昔芬对高血压脑出血模型大鼠早期脑损伤的神经保护作用研究

目的:研究他莫昔芬对高血压脑出血模型大鼠早期脑损伤的神经保护作用。方法:取大鼠随机分为假手术组、模型组和高、中、低剂量实验(他莫昔芬10、5、2.5 mg/kg)组,每组48只,除假手术组外其余各组大鼠建立高血压脑出血模型,建模后分别腹腔注射相应药物,每24 h给药1次。考察给药后4、8、12、24、72 h和7 d时各组大鼠血肿周围脑组织中Fas相关死亡域蛋白(FADD)的阳性细胞数、凋亡细胞数、脑水肿情况以及脑组织形态学变化情况。结果:与假手术组比较,其余各组大鼠不同时间的脑组织中FADD阳性细胞数、凋亡细胞数、脑水肿比例均明显增加(P<0.05);与模型组比较,低剂量实验组大鼠的FADD阳性细胞数(给药后24、72 h)、凋亡细胞数(给药后24、72 h和7 d)和脑组织含水量(给药后72 h)均明显减少(P<0.05),中、高剂量实验组大鼠的FADD阳性细胞数(给药后8、12、24、72 h)、凋亡细胞数(给药后12、24、72 h和7 d)和脑组织含水量(给药后12、24、72 h和7 d)均明显减少(P<0.05),各剂量实验组大鼠血肿周围组织水肿范围变小、程度减轻,炎症细胞的浸润减轻,固缩细胞减少,肿胀细胞增多,细胞周围间隙变小,且均呈剂量依赖性。结论:他莫昔芬能够呈剂量依赖性地抑制高血压脑出血模型大鼠的FADD阳性细胞表达,减少脑组织细胞的凋亡,同时减轻脑出血后的脑水肿,发挥显著的神经保护作用。

Neuroprotection of Tamoxifen on Early Brain Injury in Rats with Hypertensive Cerebral Hemorrhage

OBJECTIVE：To study the neuroprotection of tamoxifen on early brain injury in rats with hypertensive cerebral hemorrhage.METHODS：Rats were randomly divided into sham operation group,model group,high-dose,medium-dose and lowdose trial（tamoxifen 10,5,2.5 mg/kg）groups with 48 rats in each group.Hypertensive cerebral hemorrhage model was established in those groups except sham operation group.After modeling,they were given relevant medicine intraperitoneally every 24 h.The amount of FADD positive cell and apoptotic cell,cerebral edema and morphological change in cerebral tissue around hematoma in rats were investigated 4 h,8 h,12 h,24 h,72 h and 7 d after medication.RESULTS：Compared with sham operation group,the amount of FADD positive cell and apoptotic cell,the proportion of cerebral edema in cerebral tissue of rats were increased in each group at different time points（P〈0.05）.Compared with model group,the amount of FADD positive cell（24 h,72 h after medication）and apoptotic cell（24 h,72 h and 7 d after medication）,the proportion of cerebral edema（72 h after medication）were significantly decreased in low-dose trial group（P〈0.05）;the amount of FADD positive cell（8 h,12 h,24 h,72 h after medication）and apoptotic cell（12 h,24 h,72 h and 7 d after medication）,the proportion of cerebral edema（12 h,24 h,72 h and 7 d after medication）were significantly decreased in medium-dose and high-dose trial groups（P〈0.05）;in trial groups,the edema of cerebral tissue around hematoma was relieved in scope and degree;the infiltration of inflammatory cells reduced;pyknotic cells decreased,while cell swelling increased;the peripheral clearance of cells became smaller in dose-dependant manner.CONCLUSIONS：Tamoxifen can inhibit the expression of FADD positive cells in rats with hypertensive cerebral hemorrhage in dose-dependant manner,reduce the apoptosis of cerebral cell,and relieve cerebral edema after cerebral hemorrhage to play a neuroprotective role.