Sato Kota, Yamashita Toru, Kurata Tomoko, Fukui Yusuke, Hishikawa Nozomi, Deguchi Kentaro, Abe Koji
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
J Stroke Cerebrovasc Dis. 2014 Nov-Dec;23(10):2511-2519. doi: 10.1016/j.jstrokecerebrovasdis.2014.02.019. Epub 2014 Sep 20.
Telmisartan, an angiotensin receptor blocker with high lipid solubility, also called metabo-sartan, not only reduces blood pressure (BP), but also ameliorates inflammation in the cerebral cortex and in adipose tissue. We examined the effects of telmisartan on inflammatory responses of monocyte chemotactic protein-1, tumor necrosis factor-α, and ionized calcium-binding adapter molecule 1 in the brain of spontaneously hypertensive rat stroke-resistant (SHR-SR) after transient middle cerebral artery occlusion (tMCAO). At 12 weeks of age, SHR-SR received tMCAO for 90 minutes and were divided into 3 groups, that is, the vehicle group, a low-dose telmisartan group (.3 mg/kg/day), and a high-dose telmisartan group (3 mg/kg/day). Immunohistological analysis was performed when rats became 6, 12 and 18 months old. Monocyte chemotactic protein-1, tumor necrosis factor-α, and ionized calcium-binding adapter molecule 1 cells (/mm(2)) immunoreactivities increased with age in the cerebral cortex and hippocampus of the vehicle group, suggesting strong and persistent inflammatory changes in SHR-SR after tMCAO up to 18 months of age. On the other hand, a low dose of telmisartan significantly reduced such inflammatory changes without lowering BP, whereas a high dose of telmisartan showed a few additional improvements, including the lowering of BP throughout 6-18 months of age. The present study suggests that persistent hypertension after tMCAO caused a long-lasting inflammatory response in the SHR-SR brain, and that even a low dose of telmisartan reduced continuous inflammation without lowering BP via its pleiotropic effects in the SHR-SR brain. A high dose of telmisartan had a few additional benefits, including lowering BP.
替米沙坦是一种具有高脂质溶解度的血管紧张素受体阻滞剂，也称为美卡素，它不仅能降低血压，还能改善大脑皮层和脂肪组织中的炎症。我们研究了替米沙坦对短暂性大脑中动脉闭塞（tMCAO）后自发性高血压抗中风大鼠（SHR-SR）大脑中单核细胞趋化蛋白-1、肿瘤坏死因子-α和离子钙结合衔接分子1炎症反应的影响。12周龄时，SHR-SR接受90分钟的tMCAO，并分为3组，即载体组、低剂量替米沙坦组（0.3mg/kg/天）和高剂量替米沙坦组（3mg/kg/天）。当大鼠6、12和18个月大时进行免疫组织学分析。载体组大脑皮层和海马中单核细胞趋化蛋白-1、肿瘤坏死因子-α和离子钙结合衔接分子1细胞（/mm²）免疫反应性随年龄增加，表明tMCAO后直至18个月龄，SHR-SR中存在强烈且持续的炎症变化。另一方面，低剂量替米沙坦在不降低血压的情况下显著减少了此类炎症变化，而高剂量替米沙坦显示出一些额外的改善，包括在6至18个月龄期间降低血压。本研究表明，tMCAO后持续的高血压在SHR-SR大脑中引起了持久的炎症反应，并且即使是低剂量的替米沙坦也能通过其在SHR-SR大脑中的多效性作用减少持续炎症而不降低血压。高剂量替米沙坦还有一些额外的益处，包括降低血压。
