Pien-Tze-Huang protects cerebral ischemic injury by inhibiting neuronal apoptosis in acute ischemic stroke rats
Pien-Tze-Huang protects cerebral ischemic injury by inhibiting neuronal apoptosis in acute ischemic stroke rats
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DOI：
10.1016/j.jep.2018.03.018
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发表时间：
2018-06-12
影响因子：
5.4
通讯作者：
Peng, Jun
中科院分区：
文献类型：
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作者：
Zhang, Xiaoqin;Zhang, Yiping;Peng, Jun
民族药理学相关性：片仔癀（PZH）是用于治疗中风的著名中药配方。然而，PZH对急性缺血性脑卒中的保护作用及其机制仍有待探讨。本研究目的：探讨PZH对急性脑缺血损伤大鼠神经元凋亡的保护作用，并探讨其潜在机制。材料与方法：研究PZH对短暂性大脑中动脉闭塞所致急性缺血性脑卒中大鼠的影响，以及线粒体介导的细胞色素C（Cyt C）、Bax、Bcl-xl、评估P53、caspase-3和caspase-9以及AKT和糖原合成酶激酶-3β（GSK-3β）。结果：PZH治疗（180mg/kg）4天可显着减少急性缺血性脑卒中大鼠的脑梗塞体积，改善神经功能缺损，减轻炎症反应并抑制神经元凋亡。此外，PZH 治疗显着降低了细胞质 Cyt C、Bax、P53、cleaved caspase-3 和 cleaved caspase-9 水平，但升高了线粒体 Cyt C 和 Bcl-xl 水平。 PZH 治疗还增加了 AKT 和 GSK-3 beta 的磷酸化。结论：PZH 有效保护大脑免受体内脑缺血/再灌注损伤，抑制线粒体介导的神经元凋亡以及减弱炎症反应可能与此作用有关。本研究为PZH治疗急性脑缺血性脑卒中提供了实验依据，为其防治缺血性脑卒中提供了新的思路。
Ethnopharmacological relevance: Pien-Tze-Huang (PZH) is a famous formula of traditional Chinese medicine used to treating stroke. However, the protective effect of PZH and its mechanisms in acute ischemic stroke remain to be explored.Aim of the study: To investigate the protective effect of PZH on neuronal apoptosis in acute cerebral ischemic injury rats and explore its underlying mechanisms.Materials and methods: The effects of PZH were studied in acute ischemic stroke rats induced by transient middle cerebral artery occlusion, and the mitochondria-mediated apoptotic proteins including cytochrome C (Cyt C), Bax, Bcl-xl, P53, caspase-3, and caspase-9 as well as AKT and glycogen synthase kinase-3 beta (GSK-3 beta) were assessed.Results: Four days of PZH treatment (180 mg/kg) could significantly reduce cerebral infarct volume, improve neurological deficit, attenuate inflammatory response, and inhibit neuronal apoptosis in acute ischemic stroke rats. Moreover, PZH treatment significantly decreased cytosolic Cyt C, Bax, P53, cleaved caspase-3, and cleaved caspase-9 levels, but elevated mitochondrial Cyt C and Bcl-xl levels. PZH treatment also increased phosphorylation of AKT and GSK-3 beta.Conclusion: PZH potently protects the brain from cerebral ischemia/reperfusion injury in vivo, and inhibiting mitochondria-mediated neuronal apoptosis as well as attenuating inflammatory responses may be involved in this effect. This study provides experimental basis of PZH in treating acute cerebral ischemic stroke, which would provide some novel insights for its prevention and treatment of ischemic stroke.