靛玉红抑制自发性蛛网膜下腔出血早期脑损伤的研究

Inhibition effect of indirubin on early brain injury after spontaneous subarachnoid hemorrhage

目的:探讨靛玉红减轻自发性蛛网膜下腔出血(SAH)小鼠早期脑损害的作用。方法:90只雄性C57BL/6J小鼠随机分为假手术组、SAH+生理盐水组及SAH+靛玉红组,用血管内刺破法建立SAH模型。干湿重法检测脑含水量,神经病学评分评价小鼠的神经功能损伤,TUNEL法检测出血侧脑皮层及海马凋亡神经元的变化。结果:SAH总病死率为23.3%,其中SAH+生理盐水组病死率为24.1%,SAH+靛玉红组病死率为21.8%,差异无统计学意义(P>0.05)。神经病学评分,SAH+生理盐水组24、72 h分别为11.13±2.45、13.81±2.46,SAH+靛玉红组分别为12.55±2.11、16.32±1.09,各组间各时间点比较差异有统计学意义(P<0.05)。在出血侧大脑半球,SAH+靛玉红组脑含水量较SAH+生理盐水组脑含水量减少明显[(77.57±0.35)%vs(78.12±0.47)%,P<0.05];SAH+靛玉红组出血侧脑皮层及海马区TUNEL法检测阳性细胞与SAH+生理盐水组比较明显减少(P<0.05)。结论:靛玉红可减轻SAH后的脑水肿、抑制脑皮层和海马神经元的变性凋亡,明显改善SAH小鼠的神经功能损伤。

Objective To investigate the inhibition effect of indirubin on early brain injury after spontaneous subarachnoid hemorrhage. Methods Ninety male adult C57BL/6J mice were randomly divided into 3 groups： sham group, SAH ＋vehicle group and SAH ＋Indirubin group. Subarachnoid hemorrhage model was established by endovascular puncture method, and the blood flow of bleeding cerebral hemisphere was measured by laser Doppler flowmeter. The wet-dry weighing method was performed to measure the brain water content.The neurological appraisal was evaluated by neurological score. The apoptosis of neuron in the cortex and hippocampus was examined by TUNEL staining. Results SAH total mortality was 23.3%. Mortality showed statistical difference between SAH＋ vehicle group （24.1%） and SAH＋Indirubingroups （21.8%）.The neurological scores of the SAH＋vehicle group were 11.13 ± 2.45,13.81 ± 2.46 at 24, 72 h, which was higher than SAH＋ lndirubin group（12.55 ± 2.11,16.32 ± 1.09）. There were significant difference between groups at the same time point （P 〈 0.05）. At the bleeding cerebral hemisphere, brain water content of SAH＋ Indirubin group was （77.57 ± 0.35）%, which was better than SAH＋vehicle group （78.12 ± 0.47）% （P 〈 0.05）. The TUNEL positive cells rate of Cortex and hippo＇campus in SAH＋ Indirubin group are lower than SAH＋vehicle group （P 〈 0.05）. Conclusion Indirubin can relieve cerebral edema, reduce apoptosis of the cerebral cortex and hippocampal neurons, and improve early neurological function of SAH mice.