Cerebral ischemia-induced apoptosis and necrosis in normal and diabetic rats: Effects of insulin and C-peptide
Cerebral ischemia-induced apoptosis and necrosis in normal and diabetic rats: Effects of insulin and C-peptide
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DOI：
10.1016/j.brainres.2006.04.060
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发表时间：
2006-06-22
期刊：
影响因子：
2.9
通讯作者：
Dunbar, Joseph C.
中科院分区：
文献类型：
--
作者：
Rizk, Natalie N.;Rafols, Jose A.;Dunbar, Joseph C.
神经元凋亡已被证明是与糖尿病相关的神经功能缺陷的重要因素，并且这些缺陷在缺血后被夸大。与非糖尿病大鼠相比，糖尿病大鼠具有增加的细胞凋亡基础水平，并且先前已经证明，与非糖尿病大鼠相比，在大脑中动脉闭塞（MCAO）后，糖尿病动物中的梗死体积更大。在这项研究中，我们评估了急性和慢性的影响，胰岛素和/或C-肽对中枢神经系统坏死和细胞凋亡的非糖尿病和链脲佐菌素诱导的糖尿病大鼠MCAO再灌注。两个大脑区域，感觉运动皮层（层5和6）和海马CA 1和CA 3部门（锥体细胞层），进行了分析，使用TUNEL和Caspase-3免疫反应性细胞凋亡。慢性给药低维持浓度的胰岛素（2 U/kg），或急性给药胰岛素（2 U/kg）与或不与C-肽，没有改变病变体积或基础水平的细胞凋亡或细胞凋亡水平的动物进行2小时MCAO，随后24小时再灌注。然而，无论是急性或慢性管理的高浓度胰岛素（12 U/kg）显着减少病变体积和细胞凋亡后2小时MCAO 24小时再灌注。高剂量胰岛素治疗也降低了细胞凋亡的基础水平。我们的结论是，在糖尿病大鼠缺血和再灌注慢性胰岛素治疗降低了基础凋亡水平，急性和慢性胰岛素减少了MCAO诱导的病变体积和细胞凋亡。有或没有C肽的维持胰岛素浓度没有影响。(c)2006 Elsevier B. V.保留所有权利。
Neuronal apoptosis has been demonstrated to be a significant factor in neurological deficiencies associated with diabetes, and these deficiencies are exaggerated following ischemia. Diabetic rats have an increased basal level of apoptosis compared to non-diabetics and it has been previously demonstrated that infarct volumes were greater in diabetic animals following middle cerebral artery occlusion (MCAO) when compared to non-diabetics. In this study, we evaluated both the acute and chronic effects of insulin and/or C-peptide on CNS necrosis and apoptosis in non-diabetic and streptozotocin-induced diabetic rats following MCAO with reperfusion. Two brain areas, the sensori-motor cortex (layers-5 and 6) and the CA1 and CA3 sectors (pyramidal cell layers) of the hippocampus, were analyzed for apoptosis using TUNEL and Caspase-3 immunoreactivity. The chronic administration of a low maintenance concentration of insulin (2 U/kg), or the acute administration of insulin (2 U/kg) with or without C-peptide, did not alter the lesion volume or basal levels of apoptosis or the apoptotic levels in animals subjected to 2-h MCAO followed by 24-h reperfusion. However, both the acute or chronic administration of a high concentration of insulin (12 U/kg) significantly decreased lesion volume and apoptosis subsequent to 2-h MCAO followed by 24-h reperfusion. High dose insulin treatment also decreased the basal level of apoptosis. We conclude that in diabetic rats subjected to ischemia and reperfusion chronic insulin treatment decreased the basal apoptotic level, and both acute and chronic insulin decreased the MCAO-induced lesion volume and apoptosis. Maintenance insulin concentrations with or without C-peptide were without effect. (c) 2006 Elsevier B.V. All rights reserved.