Long-term amelioration of telmisartan on metabolic syndrome-related molecules in stroke-resistant spontaneously hypertensive rat after transient middle cerebral artery occlusion.
Long-term amelioration of telmisartan on metabolic syndrome-related molecules in stroke-resistant spontaneously hypertensive rat after transient middle cerebral artery occlusion.
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替米沙坦对短暂大脑中动脉闭塞后脑卒中抵抗性自发性高血压大鼠代谢综合征相关分子的长期改善作用。
DOI：
10.1016/j.jstrokecerebrovasdis.2014.06.012
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Abe K.
中科院分区：
文献类型：
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作者：
Deguchi K;Kurata T;Fukui Y;Liu W;Yun Z;Omote Y;Sato K;Kono S;Hishikawa N;Yamashita T;Abe K.
替米沙坦不仅有望改善高血压，而且作为代谢性沙坦也有望改善代谢综合征。我们研究了替米沙坦对短暂性大脑中动脉闭塞（tMCAO）后抗卒中自发性高血压大鼠（SHR-SR）代谢综合征相关分子如胰岛素受体（IR）、过氧化物酶体增殖物激活受体γ (PPAR-γ)和血管紧张素2型1受体（AT1R）的影响，方法是在0（对照品）、0（对照品）和0（对照品）时给药替米沙坦。术后从3月龄起给予3mg /kg/天（低剂量）或3mg /kg/天（高剂量），并在6、12和18月龄时进行免疫组织学分析。与载药组相比，2个替米沙坦组在tMCAO后6 ~ 18个月剂量依赖性地减少了同侧大脑皮层中IR和at1r阳性神经元的数量。另一方面，在6 ~ 18个月期间，2个替米沙坦组PPAR-γ阳性神经元数量呈剂量依赖性增加。本研究提示替米沙坦剂量依赖性改善了SHR-SR脑卒中后代谢综合征相关的变化，具有直接保护作用（低剂量）和附加益处，即高剂量的降压作用，对tMCAO后的长期保护。
Telmisartan is expected to ameliorate not only hypertension, but also metabolic syndrome as a metabosartan. We examined the effects of telmisartan on metabolic syndrome-related molecules such as insulin receptor (IR), peroxisome proliferator-activated receptor gamma (PPAR-γ), and angiotensin 2 type 1 receptor (AT1R) in stroke-resistant spontaneously hypertensive rat (SHR-SR) after transient middle cerebral artery occlusion (tMCAO), by administering telmisartan at either 0 (vehicle), .3 mg/kg/day (low dose), or 3 mg/kg/day (high dose), postoperatively, from 3 months of age and performed immunohistologic analysis at 6, 12, and 18 months of age. Compared with the vehicle group, the 2 telmisartan groups dose dependently decreased the number of IR- and AT1R-positive neurons in the cerebral cortex in the ipsilateral cerebral cortex from 6 to 18 months after tMCAO. On the other hand, the number of PPAR-γ-positive neurons increased in a dose-dependent manner in the 2 telmisartan groups from 6 to 18 months. The present study suggests that telmisartan dose-dependently ameliorated metabolic syndrome-related changes in the poststroke brain of SHR-SR with a direct protective effect (low dose) and an additive benefit, an antihypertensive effect at a high dose, for long-term protection after tMCAO.