细胞特异性受体盐:脑卒中未来的治疗目标?
Neural Regen Res: 细胞特异性受体盐:脑卒中未来的治疗目标?
来自美国北俄亥俄大学,Sophocles Chrissobolis 教授认为盐皮质激素受体是一种肾上皮细胞,它在液体和电解质平衡中具有重要作用。除了可以在肾脏中表达,许多研究已经报道盐皮质激素受体在非上皮组织中也能表达,包括心肌细胞、血管细胞(包括内皮细胞和平滑肌细胞)、免疫细胞和大脑。而盐皮质激素受体在大脑的几个区域中表达尤其高。盐皮质激素受体拮抗剂是通过防止内皮功能障碍、氧化应激,血管重塑和脑部炎症进而实现对脑卒中、脑血管病模型的有效作用。在脑卒中自发性高血压大鼠中,螺内酯治疗会改善脑血管内皮依赖性舒张,增加大脑中动脉的腔和外径,甚至当高血压时降低并完善墙/管腔比率,这表明盐皮质激素受体拮抗剂对脑血管系统是有好处的,即使脑血管系统已发生病理性变化。
盐皮质激素受体拮抗剂在缺血性脑卒中条件下是有益的,并且盐皮质激素受体拮抗剂、依普利酮和螺内酯对脑缺血实验模型也具有保护作用。预处理依普利酮不仅可以减少缺血区面积,同时也改善了局灶性大脑中动脉闭塞小鼠的神经功能缺损。靶向盐皮质激素受体在特定细胞类型中的治疗剂开发让脑卒中治疗向前迈进了极有意义的一步。相关内容发表在《中国神经再生研究(英文版)》杂志2016年8月8期。
Article: " Cell-specific mineralocorticoid receptors: future therapeutic targets for stroke?" by Quynh N. Dinh1, Grant R. Drummond1, Christopher G. Sobey1, Sophocles Chrissobolis2 (1 Vascular Biology & Immunopharmacology Group, Cardiovascular Disease Program and Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia; 2 Department of Pharmaceutical and Biomedical Sciences, Raabe College of Pharmacy, Ohio Northern University, Ada, OH, USA)
Dinh QN, Drummond GR, Sobey CG, Chrissobolis S (2016) Cell-specific mineralocorticoid receptors: future therapeutic targets for stroke? Neural Regen Res 11(8):1230-1231.
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细胞特异性受体盐:脑卒中未来的治疗目标?
盐皮质激素受体是一种肾上皮细胞,它在液体和电解质平衡中具有重要作用。除了可以在肾脏中表达,许多研究已经报道盐皮质激素受体在非上皮组织中也能表达,包括心肌细胞、血管细胞(包括内皮细胞和平滑肌细胞)、免疫细胞和大脑。而盐皮质激素受体在大脑的几个区域中表达尤其高。盐皮质激素受体拮抗剂是通过防止内皮功能障碍、氧化应激,血管重塑和脑部炎症进而实现对脑卒中、脑血管病模型的有效作用。在脑卒中自发性高血压大鼠中,螺内酯治疗会改善脑血管内皮依赖性舒张,增加大脑中动脉的腔和外径,甚至当高血压时降低并完善墙/管腔比率,这表明盐皮质激素受体拮抗剂对脑血管系统是有好处的,即使脑血管系统已发生病理性变化。
盐皮质激素受体拮抗剂在缺血性脑卒中条件下是有益的,并且盐皮质激素受体拮抗剂、依普利酮和螺内酯对脑缺血实验模型也具有保护作用。预处理依普利酮不仅可以减少缺血区面积,同时也改善了局灶性大脑中动脉闭塞小鼠的神经功能缺损。靶向盐皮质激素受体在特定细胞类型中的治疗剂开发让脑卒中治疗向前迈进了极有意义的一步。
Cell-specific mineralocorticoid receptors: future therapeutic targets for stroke?
The mineralocorticoid receptor (MR), well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis, has aldosterone as one of its main agonists. In addition to renal expression, many studies have reported MR expression in non-epithelial tissues, including in cardiomyocytes, vascular cells (both endothelial and smooth muscle cells), immune cells and brain. MR expression is particularly high in several brain regions. MR antagonism is beneficial in the cerebral vasculature and brain in models of stroke and aldosterone excess by preventing endothelial dysfunction, oxidative stress and remodeling in the vasculature, as well as brain inflammation. In the stroke-prone spontaneously hypertensive rat (SHRSP), spironolactone treatment improved cerebral vascular endothelium-dependent dilation), increased lumen and outer diameter of middle cerebral arteries, and decreased wall/lumen ratio even when hypertension was well established, suggesting that MR antagonism is beneficial in the cerebral vasculature even after pathology has been established (reviewed in. During aldosterone excess, spironolactone inhibited cerebral vascular oxidative stress and brain inflammation in mice. MR antagonism is beneficial in the setting of ischemic stroke in that the MR antagonists, eplerenone and spironolactone, are both protective in experimental models of cerebral ischemia. Pretreatment with eplerenone not only reduced ischemic area, but it also reduced the neurological deficit in mice subjected to focal middle cerebral artery occlusion (MCAO). The development of therapeutic agents to target MR on specific cell types may represent a promising way forward in stroke therapy.
基金资助:该研究由奥克斯纳临床基金会支持。