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【Stroke】动物实验:过量摄入盐可引起神经元凋亡
Excess Salt Causes Cerebral Neuronal Apoptosis and Inflammation in Stroke-Prone Hypertensive Rats Through Angiotensin II-Induced NADPH Oxidase Activation
Eiichiro Yamamoto MD; Nobuaki Tamamaki PhD; Taishi Nakamura MD; Keiichiro Kataoka MD; Yoshiko Tokutomi PhD; Yi-Fei Dong; Masaya Fukuda MD; Shinji Matsuba MD; Hisao Ogawa MD; and Shokei Kim-Mitsuyama MD*
From the Departments of Pharmacology and Molecular Therapeutics (E.Y., T.N., K.K., Y.T., Y.-F.D., M.F., S.M., S.K.-M.), Morphological Neural Science (N.T.), and Cardiovascular Medicine (H.O.), Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
* To whom correspondence should be addressed. E-mail: kimmitsu@gpo.kumamoto-u.ac.jp.
Background and Purpose—The precise mechanism of salt-induced brain injury is unclear. We examined the detailed causative role of angiotensin II and NADPH oxidase in salt-accelerated brain injury of stroke-prone spontaneously hypertensive rats (SHRSP).
Methods—We examined the effect of salt loading on brain reactive oxygen species (ROS), inflammation, and apoptosis in SHRSP. Salt-loaded SHRSP were given vehicle, valsartan (an angiotensin AT1 receptor blocker), or hydralazine to compare their efficacy on brain injury. We also examined the efficacy of apocynin (a NADPH oxidase inhibitor) on brain injury of salt-loaded SHRSP.
Results—Cerebral NADPH oxidase activity and ROS in SHRSP were already increased at 1 week after salt loading followed by the significant increase in ED-1-positive cells and neuronal apoptosis. Thus, cerebral NADPH oxidase activation preceded cerebral inflammation and neuronal apoptosis. Despite comparable hypotensive effects between valsartan and hydralazine in salt-loaded SHRSP, valsartan reduced cerebral NADPH oxidase activity and ROS more than hydralazine being accompanied by more prevention of stroke by valsartan than hydralazine. Valsartan, but not hydralazine, prevented neuronal apoptosis, being associated with the suppression of apoptosis signal-regulating kinase 1 activation by valsartan. Moreover, cerebral inflammation was also prevented by valsartan more than hydralazine, being associated with more suppression of monocyte chemotactic protein-1 and tumor necrosis factor- expressions by valsartan. Thus, angiotensin II was directly involved in salt-induced neuronal NADPH oxidase activation, ROS, apoptosis, and inflammation in SHRSP. Apocynin attenuated the enhancement of ROS, cerebral inflammation, neuronal apoptosis, and apoptosis signal-regulating kinase 1 activation and prevented stroke in salt-loaded SHRSP, indicating the causative role of cerebral NADPH oxidase in salt-induced brain injury.
Conclusion—We obtained the evidence that excess salt, through ROS produced by angiotensin II-activated NADPH oxidase, caused cerebral neuronal apoptosis and inflammation as well as stroke in SHRSP. 本人已认领本文翻译，48小时内未提交请其他战友继续认领。 Excess Salt Causes Cerebral Neuronal Apoptosis and Inflammation in Stroke-Prone Hypertensive Rats Through Angiotensin II-Induced NADPH Oxidase Activation
Eiichiro Yamamoto MD; Nobuaki Tamamaki PhD; Taishi Nakamura MD; Keiichiro Kataoka MD; Yoshiko Tokutomi PhD; Yi-Fei Dong; Masaya Fukuda MD; Shinji Matsuba MD; Hisao Ogawa MD; and Shokei Kim-Mitsuyama MD*
From the Departments of Pharmacology and Molecular Therapeutics (E.Y., T.N., K.K., Y.T., Y.-F.D., M.F., S.M., S.K.-M.), Morphological Neural Science (N.T.), and Cardiovascular Medicine (H.O.), Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.
* To whom correspondence should be addressed. E-mail: kimmitsu@gpo.kumamoto-u.ac.jp.
Background and Purpose—The precise mechanism of salt-induced brain injury is unclear. We examined the detailed causative role of angiotensin II and NADPH oxidase in salt-accelerated brain injury of stroke-prone spontaneously hypertensive rats (SHRSP).
研究背景和研究目的-盐诱导脑损伤的准确机制还不清楚，我们检验了血管紧张素II和NADPH氧化酶在导致自发性高血压脑卒中大鼠的盐促发性脑损伤中所起的作用
Methods—We examined the effect of salt loading on brain reactive oxygen species活性氧簇 (ROS), inflammation, and apoptosis in SHRSP. Salt-loaded荷盐的 SHRSP were given vehicle, valsartan缬沙坦(an angiotensin AT1 receptor blocker), or hydralazine盐酸肼苯哒嗪to compare their efficacy on brain injury. We also examined the efficacy of apocynin夹竹桃麻素(a NADPH oxidase inhibitor) on brain injury of salt-loaded SHRSP.
方法：在自发性高血压脑卒中大鼠上，我们检测了盐负荷对脑活性氧簇（ROS），炎症以及凋亡能过的效果。我们给盐荷自发性高血压脑卒中大鼠缬沙坦（一种血管紧张素1的拮抗剂）或盐酸肼苯哒嗪作为载体，来比较其引起大脑损伤的效力。我们还检测了夹竹桃麻素（一种NADPH氧化酶抑制剂）引起盐荷自发性高血压脑卒中大鼠大脑损伤的效力。
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作者:admin@医学,生命科学 2011-02-17 05:14
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