徳島大学 教育・研究者情報データベース(EDB)

1. 徳島大学.医学研究科.医学専攻(2004年4月1日〜)

1. 島田 健司([徳島大学.病院.先端医科医療開発研究プロジェクト]/[徳島大学.病院.診療科.脳·神経·精神科.脳神経外科])

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2. (英) Kitazato T. Keiko / (日) 北里 慶子 / (読) きたざと けいこ

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3. 木内 智也

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4. 八木 謙次

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5. 多田 恵曜([徳島大学.大学院医歯薬学研究部.医学域.先端医学教育研究プロジェクト]/[徳島大学.大学院医歯薬学研究部.医学域.医科学部門.外科系.脳神経外科学])

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6. 里見 淳一郎

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7. 影治 照喜

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8. 永廣 信治

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(英) Activation of estrogen receptor- and of angiotensin-converting enzyme 2 suppresses ischemic brain damage in oophorectomized rats.

(英) Like the angiotensin II type 1 receptor blocker, endogenous estrogen (17-estradiol) is neuroprotective against cerebral ischemia; its effects are thought to be mediated by estrogen receptors (ERs). To verify the role of ERs and the brain renin-angiotensin system in estrogen-deficient rats with ischemia induced by middle cerebral artery occlusion, we compared rats subjected to oophorectomy (OVX(+)) with sham-oophorectomized rats (OVX(-)) and OVX(+) rats treated with 0.3 or 3.0 mg/kg of olmesartan for 2 weeks before middle cerebral artery occlusion. Independent of the blood pressure, the cortical infarct volume was larger in OVX(+) than in OVX(-) rats. It was smaller in olmesartan-pretreated OVX(+) rats. The expression of ER in the peri-infarct region was correlated with the reduction of cortical infarct but not that of ER or G protein-coupled estrogen receptor. Olmesartan prevented ER downregulation in the cortical peri-infarct area, without affecting ER or G protein-coupled estrogen receptor. Olmesartan also increased mRNA expression of angiotensin-converting enzyme 2, Bcl-2, and Bcl-xL and reduced angiotensin II and cleaved caspase 3. These effects were augmented by olmesartan and abolished by the ER inhibitor. In OVX(+) rats treated with the ER agonist alone, the infarct size was decreased, and the neuroprotective genes were upregulated. These findings suggest that the transactivation of neuroprotective genes and the reduction in brain angiotensin II are ER dependent and that this may augment neuroprotection together with an angiotensin II type 1 receptor blockade by olmesartan. We present the new insight that the activation of ER independent of estrogen contributes at least partly to limiting cerebral ischemic damage.

1. (英) Angiotensin II
2. (英) Angiotensin II Type 1 Receptor Blockers
3. (英) Animals
4. 血圧(blood pressure)
5. (英) Blotting, Western
6. 脳(brain)
7. (英) Brain Ischemia
8. (英) Caspase 3
9. (英) Dose-Response Relationship, Drug
10. (英) Estrogen Receptor alpha
11. (英) Female
12. 遺伝子発現(gene expression)
13. (英) Imidazoles
14. 免疫組織化学(immunohistochemistry)
15. (英) Ovariectomy
16. (英) Peptidyl-Dipeptidase A
17. (英) Pyrazoles
18. (英) Rats
19. (英) Rats, Wistar
20. (英) Receptors, Angiotensin
21. (英) Reverse Transcriptase Polymerase Chain Reaction
22. (英) Tetrazoles
23. (英) ras Proteins

1. (英) Article.Affiliation: Department of Neurosurgery, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan. s_kenji1032@yahoo.co.jp

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't