Angiotensin II Peptide Vaccine Protects Ischemic Brain Through Reducing Oxidative Stress
Angiotensin II Peptide Vaccine Protects Ischemic Brain Through Reducing Oxidative Stress
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DOI：
10.1161/strokeaha.116.016269
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发表时间：
2017-05-01
期刊：
影响因子：
8.3
通讯作者：
Morishita, Ryuichi
中科院分区：
文献类型：
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作者：
Wakayama, Kouji;Shimamura, Munehisa;Morishita, Ryuichi
背景和目的-药物不依从性是缺血性卒中预后不良的主要危险因素之一。疫苗接种因其持久效果有望解决这样的问题，但其对缺血性脑损伤的作用仍不清楚。本研究重点关注肾素-血管紧张素系统的疫苗接种，考察血管紧张素II（Ang II）肽疫苗对大鼠永久性大脑中动脉闭塞模型的影响。方法：雄性Wistar大鼠注射3次Ang II肽疫苗后置于永久性大脑中动脉闭塞模型，检测血清或脑内抗Ang II抗体水平。通过梗塞体积、脑肾素-血管紧张素系统成分以及神经变性和氧化应激标记物的差异来评估疫苗的效果。结果-Ang II 疫苗接种成功地在血清中产生了抗 Ang II 抗体，而没有伴随血压变化。血清中抗 Ang II 抗体的充足产生导致梗塞体积减少，并诱导抗 Ang II 抗体渗透到缺血半球，同时抑制 Ang II 1 型受体 mRNA 的表达。产生足够抗体的疫苗接种大鼠显示 Fluoro-Jade B 阳性细胞、血影蛋白碎片、4-羟基壬烯醛阳性细胞和 Nox 2 mRNA 表达减少。结论 - 我们的研究结果表明，Ang II 疫苗接种在脑缺血中发挥神经保护和抗氧化作用，通过抗 Ang II 抗体渗透到缺血性脑病变中，阻断肾素 - 血管紧张素系统。 Ang II 肽疫苗接种可能是治疗缺血性中风的一种有前途的方法。
Background and Purpose-Medication nonadherence is one of major risk factors for the poor outcome in ischemic stroke. Vaccination is expected to solve such a problem because of its long-lasting effects, but its effect on ischemic brain damage is still unknown. Here, we focused on vaccination for renin-angiotensin system and examined the effects of angiotensin II (Ang II) peptide vaccine in permanent middle cerebral artery occlusion model in rats.Methods-Male Wistar rats were exposed to permanent middle cerebral artery occlusion after 3x injections of Ang II peptide vaccine, and the serum or brain level of anti-Ang II antibody was examined. The effects of the vaccine were evaluated by differences in infarction volume, brain renin-angiotensin system components, and markers for neurodegeneration and oxidative stress.Results-Ang II vaccination successfully produced anti-Ang II antibodies in serum without concomitant change in blood pressure. Sufficient production of serum anti-Ang II antibody led to reduction of infarct volume and induced the penetration of anti-Ang II antibody in ischemic hemisphere, with suppressed expression of Ang II type 1 receptor mRNA. Vaccinated rats with sufficient antibody production showed the reduction of Fluoro-Jade B-positive cells, spectrin fragmentation, 4-hydroxynonenal-positive cells, and Nox 2 mRNA expression.Conclusions-Our findings indicate that Ang II vaccination exerts neuroprotective and antioxidative effects in cerebral ischemia, with renin-angiotensin system blockade by penetration of anti-Ang II antibodies into ischemic brain lesion. Ang II peptide vaccination could be a promising approach to treat ischemic stroke.