依布硒林减轻DMT1诱导的铁死亡在实验性大鼠蛛网膜下腔出血中的研究

发布时间：2018-05-05 23:33

本文选题：蛛网膜下腔出血 + 早期脑损伤　；参考：《第三军医大学学报》2017年16期

【摘要】：目的观察大鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后二价金属离子转运体(divalent metal transportor 1,DMT1)的表达变化及铁死亡情况,探讨依布硒林可能通过抑制DMT1的表达减轻铁死亡,从而对SAH后早期脑损伤起保护作用。方法血管内穿刺法构建SD大鼠SAH模型,免疫荧光检测脑皮质中DMT1、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)表达定位,Western blot检测脑皮质中SAH后72 h内各时间点及侧脑室注射依布硒林后DMT1、GPX4的表达变化,检测细胞内铁沉积情况、铁含量、脂质过氧化物产物丙二醛(malonaldehyde,MDA)等铁死亡指标,以及大鼠脑水肿和神经功能学评分变化。结果免疫荧光检测结果显示DMT1、GPX4表达于大鼠脑皮质神经元胞质内。Western blot检测结果显示,与假手术组相比,DMT1表达先升高,24 h降低后再次升高,48、72 h仍增高(P0.01);而SAH后GPX4的表达降低,24 h显著降低(P0.01),随后48、72 h继续降低(P0.01)。与SAH组、溶剂组相比,依布硒林2 mg/kg组中DMT1降低(P0.01);依布硒林4 mg/kg干预后DMT1表达降低显著(P0.01),GPX4表达增高显著(P0.01)。与SAH组、溶剂组相比,依布硒林4 mg/kg组中细胞内铁沉积减少,铁含量、MDA减少(P0.01);GSH含量、GPX4活性增加(P0.01)。神经功能学评分、脑水肿得到改善(P0.01)。结论依布硒林可能通过抑制DMT1的表达减少铁向胞内转运继而减轻铁死亡,从而对SAH后早期脑损伤起保护作用。
[Abstract]:Objective to observe the changes of divalent metal ion transporter (divalent metal transportor 1 DMT1) and iron death after subarachnoid hemorrhage (SAH) in rats, and to explore whether ibuselin may alleviate iron death by inhibiting the expression of DMT1. Thus, early brain injury after SAH plays a protective role. Methods Sprague-Dawley (SD) rat model of SAH was established by intravascular puncture. The expression of DMT1 and glutathione peroxidase 4(glutathione peroxidase 4GPX4 in cerebral cortex were detected by immunofluorescence. The expression of DMT1GPX4 in cerebral cortex was detected by Western blot at every time point after 72 h of SAH injection and intraventricular injection of ebuselenin. The intracellular iron deposition and iron content were detected. Lipid peroxides such as malondialdehyde (MDA), malonaldehyde( MDA), and brain edema and neurological scores in rats. Results the results of immunofluorescence assay showed that DMT1GPX4 was expressed in the cytoplasm of rat cortical neurons. Western blot assay showed that DMT1GPX4 was expressed in the cytoplasm of rat cortical neurons. Compared with the sham-operated group, the expression of DMT1 increased at first and decreased at 24 h, then increased again at 48 h and then increased at 72 h, while the expression of GPX4 decreased significantly at 24 h after SAH, and continued to decrease at 48 h after operation. Compared with SAH group and solvent group, DMT1 in Ebuselin 2 mg/kg group decreased P0.01N, and DMT1 expression decreased significantly after Ebuselin 4 mg/kg intervention. Compared with SAH group and solvent group, Ibuselin 4 mg/kg group had less iron deposition and lower iron content. Neurological function score, brain edema was improved (P 0.01). Conclusion Ebuselenol may play a protective role in early brain injury after SAH by inhibiting the expression of DMT1 and reducing iron transport to the cell and then reducing iron death.
【作者单位】：重庆医科大学附属第一医院神经外科;
【基金】：国家自然科学基金面上项目(81371309) 重庆市科委自然科学基金(CSTC2012jjA10109) 国家临床重点专科建设项目经费资助项目(财社[2011]170号)~~
【分类号】：R743.35

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