Ginaton 通过诱导自噬和维持线粒体稳态来改善缺血性中风大鼠的神经功能。,Neuropsychiatric Disease and Treatment

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Ginaton 通过诱导自噬和维持线粒体稳态来改善缺血性中风大鼠的神经功能。
Neuropsychiatric Disease and Treatment ( IF 2.5 ) Pub Date : 2019-07-03 , DOI: 10.2147/ndt.s205612
Xiaoqiang Li ₁ , Deli Zhang ₁ , Yinliang Bai ₁ , Jiyuan Xiao ₁ , Haisheng Jiao ₁ , Rongxia He ₂

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目的本研究旨在证实银杏叶提取物（Ginaton）对大脑中动脉闭塞（MCAO）大鼠再灌注后24 h缺血性神经元损伤的保护作用，并进一步揭示其可能的作用机制。方法成年雄性Sprague-Dawley大鼠采用MCAO建模2 h。将大鼠分为三组：假手术组、模型组和 Ginaton (50 mg/kg)。所有动物从再灌注后 24 小时开始每天接受一次治疗，持续 14 天。MCAO 后 1、7 和 14 天进行改良神经严重程度评分测试，MCAO 后仅 14 天进行光束行走测试。实施苏木精-伊红应变以测量梗塞体积并进行免疫组织化学分析以计算缺血性皮质半影中的神经元数量。Western印迹用于评估自噬（Beclin1，LC3，AMPK，mTOR，ULK），线粒体动态蛋白（Parkin，DRP1，OPA1）和细胞凋亡（Bcl-2，Bax）的表达。结果用 Ginaton 治疗 14 天后，神经功能缺损评分降低，运动功能恢复促进，梗塞面积显着减小。此外，Ginaton 还减轻了缺血半影区 NeuN 阳性细胞的损失。在缺血皮层，Ginaton增加Beclin1和LC3-Ⅱ的表达，升高AMPK、mTOR和ULK1，并诱导自噬。此外，Ginaton 治疗上调 Parkin、DRP1 和 OPA1，并在 MCAO 再灌注损伤后 14 天内提高 Bcl-2/Bax 的比率。结论 Ginaton 在 MCAO 后 24 h 首次给药对 MCAO 大鼠表现出明显的神经保护作用。

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Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis.

PURPOSE The present study was carried out to confirm the protective effect of extract of Ginkgo biloba (Ginaton) against ischemic neuronal damage post-treatment at 24 h after reperfusion in rats with middle cerebral artery occlusion (MCAO) and further reveal its possible mechanisms. METHODS Adult male Sprague-Dawley rats were modeled by MCAO for 2 h. The rats were divided into three groups: sham, model, and Ginaton (50 mg/kg). All animals received treatment once a day for 14 days from 24 h after reperfusion. Modified neurological severity score test was performed in 1, 7 and 14 days after MCAO, and beam walking test was performed only 14 days after MCAO. Hematoxylin-eosin straining was implemented to measure infarct volume and immunohistochemical analysis was performed to calculate the number of neurons in ischemic cortex penumbra. Western blot was used to evaluate the expression of autophagy (Beclin1, LC3, AMPK, mTOR, ULK), mitochondrial dynamic protein (Parkin, DRP1, OPA1) and apoptosis (Bcl-2, Bax). RESULTS Post-treatment with Ginaton for 14 days decreased neurological deficit score, promoted the recovery of motor function, and noticeably reduced infarct size. Besides, Ginaton also alleviated the loss of NeuN-positive cells in ischemic cortex penumbra. In ischemic cortex, Ginaton increased the expression of Beclin1 and LC3-Ⅱ, elevated the AMPK, mTOR and ULK1, and induced autophagy. Moreover, Ginaton treatment upregulated Parkin, DRP1, and OPA1, and elevated the ratio of Bcl-2/Bax in 14 days after MCAO reperfusion injury. CONCLUSION Ginaton exhibited obvious neuroprotective effects in MCAO rats with initial administered 24 h after MCAO. The mechanism of Ginaton included induction of autophagy via activation of the AMPK pathway, maintenance of mitochondrial homeostasis and inhibition of apoptosis.

更新日期：2019-11-01

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