School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Pharmacy, Fifth Medical Center of PLA General Hospital, Beijing, China.
J Pharm Pharmacol. 2021 Mar 4;73(2):272-280. doi: 10.1093/jpp/rgaa028.
Stroke 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.
A 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.
The 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).
L-borneol can achieve brain protection by downregulating the excessive expression of MCU-related signalling pathway and further inhibiting the apoptosis of neurons during pMCAO.
脑卒中是全球范围内导致残疾和死亡的主要原因之一，其中缺血性脑卒中是最常见的亚型。此外，我们发现龙脑对脑缺血具有明显的治疗作用。本研究旨在通过线粒体钙单向转运体（MCU）相关的凋亡级联探讨龙脑在永久性大脑中动脉闭塞（pMCAO）大鼠中的潜在作用机制。
采用 pMCAO 模型模拟脑缺血，评估神经功能。TTC 染色观察脑梗死情况。HE 染色反映大鼠海马和皮质的病理生理变化。进一步检测 MCU 相关信号和凋亡信号通路的基因和蛋白水平。
高、中、低剂量龙脑组（H-B 组、M-B 组、L-B 组）24 h 时的神经功能评分均显著低于模型组（P<0.05，P<0.01）。高、中剂量龙脑可逆转脑梗死面积，与尼莫地平相似。HE 染色后，H-B 组和 M-B 组细胞排列整齐、密集，形态结构基本正常。高剂量龙脑可显著降低 Apaf-1、Bad 和 Caspase-3 基因和蛋白水平，增加 Bcl-2 表达（P<0.05，P<0.01）。此外，与模型组相比，H-B 组 MCU 基因和蛋白表达均显著降低（P<0.05，P<0.01）。IDH2 的表达与 MCU 相似，但与 MEP 不同（P<0.05，P<0.01）。
龙脑可通过下调 pMCAO 时 MCU 相关信号通路的过度表达，进一步抑制神经元凋亡，实现脑保护作用。
