Pioglitazone exerts protective effects against stroke in stroke-prone spontaneously hypertensive rats, independently of blood pressure
Pioglitazone exerts protective effects against stroke in stroke-prone spontaneously hypertensive rats, independently of blood pressure
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DOI：
10.1161/strokeaha.107.486522
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发表时间：
2007-11-01
期刊：
影响因子：
8.3
通讯作者：
Kim-Mitsuyama, Shokei
中科院分区：
文献类型：
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作者：
Nakamura, Taishi;Yamamoto, Eiichiro;Kim-Mitsuyama, Shokei
背景和目的-最近的亚组分析表明，吡格列酮可降低2型糖尿病患者复发性卒中的风险。然而，吡格列酮预防卒中的潜在机制尚不清楚。我们的目的是研究吡格列酮对大鼠高血压性卒中的作用。kg（-1）。d（-1））口服给药于易卒中的自发性高血压大鼠（SHRSP），以检查对高血压诱导的偶发性卒中、脑血管损伤、脑炎症、氧化应激和血管内皮功能障碍的影响。（P < 0.05），抑制大脑中动脉（P < 0.05）和脑微血管重构（P < 0.05），抑制脑巨噬细胞浸润（P <0.05），抑制脑单核细胞趋化蛋白-1和肿瘤坏死因子-α表达上调（P < 0.01）。吡格列酮治疗显著延迟SHRSP脑卒中症状的发生和死亡（P < 0.05）。吡格列酮对SHRSP脑血管损伤和卒中的这些有益作用与通过抑制NADPH氧化酶activity.Conclusions减少脑和血管超氧化物有关-我们的工作提供了第一个证据表明吡格列酮通过改善血管内皮功能障碍，抑制脑炎症，减少氧化应激，显着防止高血压引起的脑血管损伤和卒中。吡格列酮的这些有益作用与血压或血糖值无关。因此，吡格列酮似乎是治疗2型糖尿病伴高血压患者卒中的潜在药物。
Background and Purpose - Very recent subgroup analysis from the PROspective pioglitAzone Clinical Trial In macroVascular Events has shown that pioglitazone reduces the risk of recurrent stroke in type 2 diabetic patients. However, the underlying mechanism of stroke prevention by pioglitazone is unknown. Our aim was to examine the effect of pioglitazone on hypertension-based stroke in rats.Methods - Pioglitazone (1 mg . kg(-1) . d(-1)) was orally administered to stroke-prone spontaneously hypertensive rats (SHRSP) to examine the effect on incidental stroke, cerebrovascular injury, brain inflammation, oxidative stress, and vascular endothelial dysfunction induced by hypertension.Results - Treatment of SHRSP with pioglitazone for 4 weeks, without affecting blood pressure and blood glucose values, improved vascular endothelial dysfunction (P < 0.05), suppressed remodeling of the middle cerebral artery (P < 0.05) and brain microvessels (P < 0.05), and inhibited brain macrophage infiltration (P < 0.05) and the upregulation of brain monocyte chemoattractant protein-1 and tumor necrosis factor-alpha expression (P < 0.01). Furthermore, pioglitazone treatment significantly delayed the onset of stroke signs and death in SHRSP (P < 0.05). These beneficial effects of pioglitazone on cerebrovascular injury and stroke in SHRSP were associated with a reduction of brain and vascular superoxide via the inhibition of NADPH oxidase activity.Conclusions - Our work provides the first evidence that pioglitazone significantly protects against hypertension-induced cerebrovascular injury and stroke by improving vascular endothelial dysfunction, inhibiting brain inflammation, and reducing oxidative stress. These beneficial effects of pioglitazone were independent of blood pressure or blood sugar values. Thus, pioglitazone appears to be a potential therapeutic agent for stroke in type 2 diabetes with hypertension.