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Metabolomic analysis and pharmacological validation of the cerebral protective effect of 3,4‑dihydroxybenzaldehyde on cerebral ischemia‑reperfusion injury.
Molecular Medicine Reports ( IF 3.4 ) Pub Date : 2022-11-11 , DOI: 10.3892/mmr.2022.12896 Yuan Luo 1 , Pu Chen 1 , Liping Yang 1 , Xiaohua Duan 1
Molecular Medicine Reports ( IF 3.4 ) Pub Date : 2022-11-11 , DOI: 10.3892/mmr.2022.12896 Yuan Luo 1 , Pu Chen 1 , Liping Yang 1 , Xiaohua Duan 1
Affiliation
3,4‑Dihydroxybenzaldehyde (DBD), one of the active components of Gastrodia elata, has a cerebral protective effect and can effectively combat cerebral ischemia/reperfusion (I/R) injury in rats. However, the metabolite profiles and underlying mechanisms associated with DBD remain unclear. To explore the level of energy metabolism and pharmacological targets in brain tissue following DBD treatment of stroke. The right middle cerebral artery of the rats was occluded for 2 h and reperfused for 24 h to simulate brain I/R injury. Pharmacological results showed that DBD reduced cerebral infarct volume, improved neurological function and increased adenosine triphosphate (ATP) content. Mitochondria are the primary sites for ATP generation and cellular energy supply and decreasing mitochondrial dysfunction can alleviate the energy expenditure of ischemic stroke. Through further experiments, it was found that mitochondrial damage was recovered following DBD treatment, which was manifested by the improvement of mitochondrial morphology under an electron microscope and the reduction of oxidative stress damage. The metabolomics of middle cerebral artery occlusion/reperfusion (MCAO/R) rat brain tissue was studied by the liquid chromatography‑tandem mass spectrometry metabolomics method. Significantly different metabolites were screened and the pathways involved included amino sugar and nucleotide sugar metabolism and pentose phosphate pathway. Finally, the present study performed targeted metabolic profiling and validated potential therapeutic targets. Uridine diphosphate N‑acetylglucosamine (UDP‑GlcNAc) levels were decreased in the MCAO/R group but significantly increased in the DBD group. TdT‑mediated dUTP nick end labeling (TUNEL) staining, hematoxylin and eosin staining and western blotting showed that brain cell apoptosis was inhibited and neuronal morphology improved. Among them, the regulatory enzyme O‑GlcNAc transferase (OGT) of UDP‑GlcNAc appeared to be significantly increased and neuronal apoptosis was inhibited following DBD treatment, which was verified by western blotting. Therefore, by analyzing mitochondrial dysfunction following I/R and the characterization of potential markers in mitochondrial energy metabolism, it was shown that OGT could inhibit neuronal apoptosis as a potential therapeutic target for brain I/R injury.
中文翻译:
3,4-二羟基苯甲醛对脑缺血再灌注损伤脑保护作用的代谢组学分析及药理验证
3,4-二羟基苯甲醛 (DBD) 是天麻的活性成分之一,具有脑保护作用,可有效对抗大鼠脑缺血/再灌注 (I/R) 损伤。然而,与 DBD 相关的代谢物概况和潜在机制仍不清楚。探讨DBD治疗脑卒中后脑组织能量代谢水平及药理靶点。阻断大鼠右侧大脑中动脉2 h,再灌注24 h,模拟脑I/R损伤。药理结果表明,DBD 可减少脑梗死体积,改善神经功能并增加三磷酸腺苷 (ATP) 含量。线粒体是 ATP 生成和细胞能量供应的主要场所,减少线粒体功能障碍可以减轻缺血性中风的能量消耗。通过进一步的实验发现,DBD处理后线粒体损伤得到恢复,表现为电镜下线粒体形态的改善和氧化应激损伤的减轻。采用液相色谱-串联质谱代谢组学方法研究了大脑中动脉闭塞/再灌注(MCAO/R)大鼠脑组织的代谢组学。筛选出显着不同的代谢物,涉及的途径包括氨基糖和核苷酸糖代谢以及磷酸戊糖途径。最后,本研究进行了有针对性的代谢分析并验证了潜在的治疗靶点。尿苷二磷酸 N-乙酰葡糖胺 (UDP-GlcNAc) 水平在 MCAO/R 组中降低,但在 DBD 组中显着升高。TdT 介导的 dUTP 缺口末端标记 (TUNEL) 染色、苏木精和伊红染色以及蛋白质印迹显示脑细胞凋亡受到抑制,神经元形态得到改善。其中,UDP-GlcNAc 的调节酶 O-GlcNAc 转移酶 (OGT) 似乎在 DBD 处理后显着增加,神经细胞凋亡受到抑制,这已通过蛋白质印迹法得到证实。因此,通过分析 I/R 后的线粒体功能障碍和线粒体能量代谢中潜在标志物的表征,
更新日期:2022-11-11
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
3,4-二羟基苯甲醛对脑缺血再灌注损伤脑保护作用的代谢组学分析及药理验证
3,4-二羟基苯甲醛 (DBD) 是天麻的活性成分之一,具有脑保护作用,可有效对抗大鼠脑缺血/再灌注 (I/R) 损伤。然而,与 DBD 相关的代谢物概况和潜在机制仍不清楚。探讨DBD治疗脑卒中后脑组织能量代谢水平及药理靶点。阻断大鼠右侧大脑中动脉2 h,再灌注24 h,模拟脑I/R损伤。药理结果表明,DBD 可减少脑梗死体积,改善神经功能并增加三磷酸腺苷 (ATP) 含量。线粒体是 ATP 生成和细胞能量供应的主要场所,减少线粒体功能障碍可以减轻缺血性中风的能量消耗。通过进一步的实验发现,DBD处理后线粒体损伤得到恢复,表现为电镜下线粒体形态的改善和氧化应激损伤的减轻。采用液相色谱-串联质谱代谢组学方法研究了大脑中动脉闭塞/再灌注(MCAO/R)大鼠脑组织的代谢组学。筛选出显着不同的代谢物,涉及的途径包括氨基糖和核苷酸糖代谢以及磷酸戊糖途径。最后,本研究进行了有针对性的代谢分析并验证了潜在的治疗靶点。尿苷二磷酸 N-乙酰葡糖胺 (UDP-GlcNAc) 水平在 MCAO/R 组中降低,但在 DBD 组中显着升高。TdT 介导的 dUTP 缺口末端标记 (TUNEL) 染色、苏木精和伊红染色以及蛋白质印迹显示脑细胞凋亡受到抑制,神经元形态得到改善。其中,UDP-GlcNAc 的调节酶 O-GlcNAc 转移酶 (OGT) 似乎在 DBD 处理后显着增加,神经细胞凋亡受到抑制,这已通过蛋白质印迹法得到证实。因此,通过分析 I/R 后的线粒体功能障碍和线粒体能量代谢中潜在标志物的表征,