Department of Neurology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.
Exp Neurol. 2011 Dec;232(2):299-308. doi: 10.1016/j.expneurol.2011.09.022. Epub 2011 Sep 22.
We investigated the changes and the molecular mechanisms of cerebral vascular damage and tested the therapeutic effects of Niaspan in type-1 streptozotocin induced diabetic (T1DM) rats after stroke. T1DM-rats were subjected to transient middle cerebral artery occlusion (MCAo) and treated without or with Niaspan. Non-streptozotocin rats (WT) were also subjected to MCAo. Functional outcome, blood-brain-barrier (BBB) leakage, brain hemorrhage, immunostaining, and rat brain microvascular endothelial cell (RBEC) culture were performed. Compared to WT-MCAo-rats, T1DM-MCAo-rats did not show an increase lesion volume, but exhibited significantly increased brain hemorrhage, BBB leakage and vascular damage as well as decreased functional outcome after stroke. Niaspan treatment of stroke in T1DM-MCAo-rats significantly attenuated BBB damage, promoted vascular remodeling and improved functional outcome after stroke. T1DM-MCAo-rats exhibited significantly increased Angiopoietin 2 (Ang2) expression, but decreased Ang1 expression in the ischemic brain compared to WT-MCAo-rats. Niaspan treatment attenuated Ang2, but increased Ang1 expression in the ischemic brain in T1DM-MCAo-rats. In vitro data show that the capillary-like tube formation in the WT-RBECs marginally increased compared to T1DM-RBEC. Niaspan and Ang1 treatment significantly increased tube formation compared to non-treatment control. Inhibition of Ang1 attenuated Niacin-induced tube formation in T1DM-RBECs. Niaspan treatment of stroke in T1DM-rats promotes vascular remodeling and improves functional outcome. The Ang1/Ang2 pathway may contribute to Niaspan induced brain plasticity. Niaspan warrants further investigation as a therapeutic agent for the treatment of stroke in diabetics.
我们研究了脑血管损伤的变化和分子机制，并测试了尼可司他在 1 型链脲佐菌素诱导的糖尿病（T1DM）大鼠中风后的治疗效果。T1DM 大鼠接受短暂性大脑中动脉闭塞（MCAo），并分别给予尼可司他或不给予尼可司他治疗。非链脲佐菌素大鼠（WT）也接受 MCAo。进行功能结果、血脑屏障（BBB）渗漏、脑出血、免疫染色和大鼠脑微血管内皮细胞（RBEC）培养。与 WT-MCAo-大鼠相比，T1DM-MCAo-大鼠的病变体积没有增加，但中风后脑出血、BBB 渗漏和血管损伤明显增加，功能结果明显降低。尼可司他治疗 T1DM-MCAo-大鼠的中风，明显减轻了 BBB 损伤，促进了血管重塑，改善了中风后的功能结果。与 WT-MCAo-大鼠相比，T1DM-MCAo-大鼠缺血脑内的血管生成素 2（Ang2）表达明显增加，而 Ang1 表达明显降低。尼可司他治疗可减轻 T1DM-MCAo-大鼠缺血脑内的 Ang2，但增加 Ang1 表达。体外数据显示，WT-RBEC 的毛细血管样管状形成与 T1DM-RBEC 相比略有增加。尼可司他和 Ang1 治疗与非治疗对照相比，明显增加了管状形成。Ang1 抑制减弱了 T1DM-RBEC 中尼可司他诱导的管状形成。尼可司他治疗 T1DM 大鼠的中风，促进了血管重塑，改善了功能结果。Ang1/Ang2 通路可能有助于尼可司他诱导的脑可塑性。尼可司他作为糖尿病中风治疗剂值得进一步研究。
