PDF(Pubmed)
Abstract：
UNASSIGNED: Oxidative stress is an important pathological process in ischemic stroke (IS). Apigenin (APG) is a natural product with favorable antioxidative effects, and some studies have already demonstrated the antioxidative mechanism of APG in the treatment of IS. However, the mechanism of APG on DNA damage and repair after IS is not clear. The aim of this study was to investigate the mechanism of APG on DNA repair after IS.
UNASSIGNED: Male Sprague-Dawley rats were used to establish a model of permanent middle cerebral artery occlusion (pMCAO) on one side, and were pre-treated with gavage of APG (30, 60, or 120 mg/kg) for 7 days. One day after pMCAO, the brain tissues were collected. Cerebral infarct volume, brain water content, HE staining and antioxidant index were analyzed to evaluated the brain damage. Molecular Docking, molecular dynamics (MD) simulation, immunohistochemistry, and Western blot were used to explore the potential proteins related to DNA damage repair.
UNASSIGNED: APG has a low binding score with DNA repair-related proteins. APG treatment has improved the volume of cerebral infarction and neurological deficits, reduced brain edema, and decreased parthanatos and apoptosis by inhibiting PARP1/AIF pathway. In addition, APG improved the antioxidative capacity through reducing reactive oxygen species and malondialdehyde, and increasing glutathione and superoxide dismutase. Also, APG has reduced DNA damage- and cell death-related proteins such as PARP1, γH2A.X, 53BP1, AIF, cleaved caspase3, Cytochrome c, and increased DNA repair by BRCA1 and RAD51 through homologous recombination repair, and reduced non-homologous end link repair by KU70.
UNASSIGNED: APG can improve nerve damage after IS, and these protective effects were realized by reducing oxidative stress and DNA damage, and improving DNA repair.
UNASSIGNED: Male Sprague-Dawley rats were used to establish a model of permanent middle cerebral artery occlusion (pMCAO) on one side, and were pre-treated with gavage of APG (30, 60, or 120 mg/kg) for 7 days. One day after pMCAO, the brain tissues were collected. Cerebral infarct volume, brain water content, HE staining and antioxidant index were analyzed to evaluated the brain damage. Molecular Docking, molecular dynamics (MD) simulation, immunohistochemistry, and Western blot were used to explore the potential proteins related to DNA damage repair.
UNASSIGNED: APG has a low binding score with DNA repair-related proteins. APG treatment has improved the volume of cerebral infarction and neurological deficits, reduced brain edema, and decreased parthanatos and apoptosis by inhibiting PARP1/AIF pathway. In addition, APG improved the antioxidative capacity through reducing reactive oxygen species and malondialdehyde, and increasing glutathione and superoxide dismutase. Also, APG has reduced DNA damage- and cell death-related proteins such as PARP1, γH2A.X, 53BP1, AIF, cleaved caspase3, Cytochrome c, and increased DNA repair by BRCA1 and RAD51 through homologous recombination repair, and reduced non-homologous end link repair by KU70.
UNASSIGNED: APG can improve nerve damage after IS, and these protective effects were realized by reducing oxidative stress and DNA damage, and improving DNA repair.
摘要：
■氧化应激是缺血性卒中（IS）的重要病理过程。芹菜素（APG）是一种具有良好抗氧化作用的天然产物，一些研究已经证明了APG治疗IS的抗氧化机制。然而,APG对IS后DNA损伤修复的机制尚不清楚。本研究的目的是探讨APG对IS后DNA修复的作用机制。
■雄性Sprague-Dawley大鼠建立一侧永久性大脑中动脉闭塞（pMCAO）模型，并用APG(30、60或120mg/kg)管饲法预处理7天。pMCAO后的一天，收集脑组织。脑梗死体积,脑含水量,HE染色和抗氧化指数分析评价脑损伤。分子对接,分子动力学（MD）模拟，免疫组织化学，用Westernblot方法探索与DNA损伤修复相关的潜在蛋白。
■APG与DNA修复相关蛋白的结合得分较低。APG治疗改善了脑梗死的体积和神经功能缺损，减少脑水肿，并通过抑制PARP1/AIF途径减少parthanatos和凋亡。此外,APG通过减少活性氧和丙二醛来提高抗氧化能力，增加谷胱甘肽和超氧化物歧化酶。此外，APG具有减少DNA损伤和细胞死亡相关蛋白,例如PARP1、γH2A。X,53BP1,AIF,caspase3，细胞色素c，BRCA1和RAD51通过同源重组修复增加了DNA修复，KU70减少了非同源末端连接修复。
■APG可以改善IS后的神经损伤，这些保护作用是通过减少氧化应激和DNA损伤来实现的，改善DNA修复。
■雄性Sprague-Dawley大鼠建立一侧永久性大脑中动脉闭塞（pMCAO）模型，并用APG(30、60或120mg/kg)管饲法预处理7天。pMCAO后的一天，收集脑组织。脑梗死体积,脑含水量,HE染色和抗氧化指数分析评价脑损伤。分子对接,分子动力学（MD）模拟，免疫组织化学，用Westernblot方法探索与DNA损伤修复相关的潜在蛋白。
■APG与DNA修复相关蛋白的结合得分较低。APG治疗改善了脑梗死的体积和神经功能缺损，减少脑水肿，并通过抑制PARP1/AIF途径减少parthanatos和凋亡。此外,APG通过减少活性氧和丙二醛来提高抗氧化能力，增加谷胱甘肽和超氧化物歧化酶。此外，APG具有减少DNA损伤和细胞死亡相关蛋白,例如PARP1、γH2A。X,53BP1,AIF,caspase3，细胞色素c，BRCA1和RAD51通过同源重组修复增加了DNA修复，KU70减少了非同源末端连接修复。
■APG可以改善IS后的神经损伤，这些保护作用是通过减少氧化应激和DNA损伤来实现的，改善DNA修复。
