Hyperlipidemia exacerbates cerebral injury through oxidative stress, inflammation and neuronal apoptosis in MCAO/reperfusion rats
Hyperlipidemia exacerbates cerebral injury through oxidative stress, inflammation and neuronal apoptosis in MCAO/reperfusion rats
复制标题
高脂血症通过氧化应激、炎症和神经元凋亡加剧 MCAO/再灌注大鼠的脑损伤
DOI：
10.1007/s00221-015-4269-x
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发表时间：
2015-10-01
影响因子：
2
通讯作者：
Hu, Xia-Min
中科院分区：
文献类型：
--
作者：
Cao, Xiao-Lu;Du, Jing;Hu, Xia-Min
最近的研究表明，高血糖症加重了短暂性脑缺血性卒中时的脑损伤。然而，它们之间的病因联系却鲜为人知。本研究以高脂血症合并脑缺血再灌注损伤（I/R）大鼠模型为基础，发现高脂饮食（HFD）诱导的高脂血症导致血清甘油三酯、胆固醇和低密度脂蛋白胆固醇显著升高，而血清高密度脂蛋白胆固醇显著降低，并伴有神经功能缺损加重，脑梗死和末端脱氧核苷酸转移酶介导的缺口末端标记阳性细胞在脑I/R大鼠与HFD饮食治疗的缺血半球。结果表明，单纯高脂血症或脑I/R均可使血清超氧化物歧化酶活性和谷胱甘肽过氧化物酶含量明显降低，丙二醛含量明显升高，高脂血症与脑I/R共存时尤为明显;同时，高脂血症还增强脑I/R诱导的细胞色素P450 2 E1（CYP 2 E1）蛋白表达和促炎因子肿瘤坏死因子-α（TNF-α）水平。α和IL-6在缺血的大脑半球。此外，与高脂血症或脑I/R单独相比，高脂血症和脑I/R的联合作用导致细胞间粘附分子-1和血管细胞粘附分子-1的蛋白表达增加。同时，高脂血症可显著增强脑I/R诱导的细胞色素c从线粒体向胞浆的转移，增强Apaf-1和caspase-3蛋白的表达，降低bcl-2蛋白的表达。结果表明，高脂血症通过协同CYP 2 E1的诱导作用加重脑缺血再灌注损伤，并通过高脂血症与脑缺血再灌注共存，进一步诱导活性氧自由基的形成、氧化应激、炎症反应和神经元凋亡。
Recent studies showed that hyperglycemia enhanced brain damage when subjected to transient cerebral ischemic stroke. However, the etiologic link between them has been less known. In the present study, based on an experimental rat's model of hyperlipidemia combined with cerebral ischemia-reperfusion injury (I/R), we herein showed that hyperlipidemia induced by high-fat diet (HFD) resulted in considerable increase in serum triglycerides, cholesterol and low-density lipoprotein cholesterol, and remarkable decrease in serum high-density lipoprotein cholesterol, which associated with an exacerbation on neurological deficit, cerebral infarct and terminal deoxynucleotidyl transferase-mediated nick end labeling-positive cells in the ischemic hemisphere of cerebral I/R rats treated with HFD diet. The data showed that serum superoxide dismutase activity and glutathione peroxides content were significantly decreased, while malondialdehyde level was obviously increased by hyperlipidemia or cerebral I/R alone, especially by coexistence of hyperlipidemia and cerebral I/R; meantime, hyperlipidemia also enhanced cerebral I/R-induced protein expression of cytochrome P450 2E1 (CYP2E1) and the levels of pro-inflammatory factors tumor necrosis factor-alpha and IL-6 in the ischemic hemispheres. Furthermore, the combined action of hyperlipidemia and cerebral I/R resulted in a protein increase expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 compared to hyperlipidemia or cerebral I/R alone. Meanwhile, this study also showed that hyperlipidemia significantly enhanced cerebral I/R-induced transfer of cytochrome c from mitochondria to cytosolic and the protein expressions of Apaf-1 and caspase-3, but also decreased cerebral I/R-induced bcl-2 protein expression. The results reveal that hyperlipidemia exacerbates cerebral I/R-induced injury through the synergistic effect on CYP2E1 induction, which further induces reactive oxygen species formation, oxidative stress, inflammation and neuronal apoptosis by coexistence of hyperlipidemia and cerebral I/R.