l-Borneol ameliorates cerebral ischaemia by downregulating the mitochondrial calcium uniporter-induced apoptosis cascade in pMCAO rats
l-Borneol ameliorates cerebral ischaemia by downregulating the mitochondrial calcium uniporter-induced apoptosis cascade in pMCAO rats
复制标题
左旋冰片通过下调 pMCAO 大鼠线粒体钙单向转运蛋白诱导的细胞凋亡级联反应改善脑缺血
DOI：
10.1093/jpp/rgaa028
复制
发表时间：
2021-03-04
影响因子：
3.3
通讯作者：
Ma，Xiao
中科院分区：
文献类型：
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作者：
Zhang，Wenwen;Wen，Jianxia;Ma，Xiao
目标中风是全世界残疾和死亡的主要原因之一，缺血性中风是最常见的亚型。而且我们发现左旋冰片对脑缺血有明显的治疗作用。本研究旨在探讨左旋冰片通过线粒体钙单向转运蛋白(MCU)相关的细胞凋亡级联对永久性大脑中动脉闭塞(pMCAO)大鼠的潜在作用机制。方法采用pMCAO模型模拟脑缺血，并评估神经功能。 TTC染色观察脑梗死情况。 HE染色也用于反映大鼠海马和皮质的病理生理变化。并在基因和蛋白水平检测MCU相关信号和凋亡信号通路。结果左旋冰片高剂量（H-B）组、中剂量左旋冰片（M-B）组和低剂量左旋冰片（L-B）组24 h神经功能评分均显着低于模型组（P<0.05，P<0.01）。高、中剂量左旋冰片可逆转脑梗塞面积，与尼莫托类似。 HE染色后，H-B组和M-B组细胞排列整齐、致密，形态结构基本正常。高剂量左旋冰片可显着降低Apaf-1、Bad、Caspase-3基因及蛋白水平，上调Bcl-2表达（P<0.05，P<0.01）。此外，与模型组相比，H-B组MCU表达在基因和蛋白水平上均显着降低（P<0.05，P<0.01）。 IDH2的表达与MCU相似，而与MEP相似(P<0.05，P<0.01)。结论左旋冰片可通过下调MCU相关信号通路的过度表达，进一步抑制pMCAO过程中神经元的凋亡来实现脑保护作用。
ObjectivesStroke is one of the leading causes of disability and death worldwide, and ischaemic stroke is the most common subtype. Moreover, we found that L-borneol has an obvious therapeutic effect on cerebral ischaemia. This study aimed to investigate the potential mechanism of L-borneol in permanent middle cerebral artery occlusion (pMCAO) rats via the mitochondrial calcium uniporter (MCU)-related apoptosis cascade.MethodsA pMCAO model was used to simulate cerebral ischaemia, and neurological function was evaluated. Cerebral infarction was observed by TTC staining. HE staining was also used to reflect the pathophysiological changes in the rat hippocampus and cortex. Furthermore, MCU-related signals and apoptosis signalling pathways were detected at both the gene and protein levels.ResultsThe neurological function scores of the high-dose L-borneol (H-B) group, medium-dose L-borneol (M-B) group and low-dose L-borneol (L-B) group were significantly lower than that of the model group at 24 h (P< 0.05,P< 0.01). High and medium doses of L-borneol could reverse the cerebral infarction area, similar to Nimotop. After HE staining, the cells in the H-B group and M-B group were neatly and densely arranged, with largely normal morphological structures. High-dose L-borneol could significantly reduce the gene and protein levels of Apaf-1, Bad and Caspase-3 and increase the expression of Bcl-2 (P< 0.05,P< 0.01). In addition, the MCU expression of the H-B group was significantly decreased compared with that of the model group at both the gene and protein levels (P< 0.05,P< 0.01). The expression of IDH2 was similar to that of MCU but not MEP (P< 0.05,P< 0.01).ConclusionL-borneol can achieve brain protection by downregulating the excessive expression of MCU-related signalling pathway and further inhibiting the apoptosis of neurons during pMCAO.