基于线粒体-炎症途径的利格列嗪对偏头痛大鼠能量代谢的影响

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2024-11-04 DOI:10.1016/j.neulet.2024.138035

Yicheng Wang , Yongli Wang , Guangxin Yue , Jingjing Lin , Xueying Liu , Liwei Wang , Yonglie Zhao

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引用次数: 0

摘要

目的评估利格列净（Lig）对硝酸甘油诱导的偏头痛的影响，并探讨其通过线粒体-炎症途径的机制：大鼠分为对照组、模型组、Lig（50 mg/kg）+Erastin组、Lig（100 mg/kg）组、Lig（50 mg/kg）组和Zolmitriptan组。通过注射硝酸甘油（NTG）引发偏头痛。对以下参数进行了测量：机械痛阈值、线粒体形态、活性氧（ROS）水平、线粒体膜电位（MMP）、三磷酸腺苷（ATP）和一氧化氮（NO）。通过 Western 印迹和免疫组织化学方法检测了神经元一氧化氮合酶（nNOS）、瞬时受体电位 A1（TRPA1）、白细胞介素 1 beta（IL-1β）、核因子-卡巴（NF-κB）和降钙素基因相关肽（CGRP）：结果：与模型组相比，Lig（100 mg/kg）组和Lig（50 mg/kg）组提高了机械痛阈，改善了线粒体的异常形态。此外，与模型组相比，Lig（100 毫克/千克）组和 Lig（50 毫克/千克）组的 ROS 和 NO 水平降低，MMP 和 ATP 水平升高。Lig（100 毫克/千克）组和 Lig（50 毫克/千克）组通过抑制某些基因的表达减少了炎症和氧化应激。当注射 Erastin 时，Lig 的效果下降，这表明 Lig 的治疗效果与 mPTP 的开放程度有关：结论：线粒体-炎症通路在调节偏头痛中起着关键作用。Lig主要通过调节线粒体-炎症途径发挥抗偏头痛作用，为偏头痛研究提供了一个新的视角，有利于偏头痛的临床应用。

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Effects of ligustrazine on energy metabolism in migraine rats based on mitochondria-inflammation pathway

Objective

To evaluate the effects of Ligustrazine (Lig) on nitroglycerin-induced migraine and explore the mechanism through the mitochondria-inflammation pathway.

Methods

Rats were divided into control, model, Lig(50 mg/kg) + Erastin, Lig(100 mg/kg), Lig(50 mg/kg), and Zolmitriptan groups. Nitroglycerin (NTG) was administered through injection to trigger a migraine. The following parameters were measured: mechanical pain threshold, mitochondrial morphology, levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), Adenosine triphosphate (ATP), and Nitric oxide (NO). The neuronal nitric oxide synthase (nNOS), transient receptor potential A1 (TRPA1), interleukin 1 beta (IL-1β), nuclear factor-kappaB (NF-κB), and calcitonin gene-related peptide (CGRP) were detected by Western blotting and immunohistochemistry.

Results

Compared with the model group, the Lig(100 mg/kg) and Lig(50 mg/kg) groups increased mechanical pain threshold as well as improved abnormal mitochondrial morphology. Moreover, compared with the model group, the Lig(100 mg/kg) and Lig(50 mg/kg) groups demonstrated reduced levels of ROS, and NO, and increased MMP, and ATP. Lig(100 mg/kg) and Lig(50 mg/kg) groups reduced inflammation and oxidative stress by inhibiting certain gene expressions. When Erastin was injected, the effectiveness of Lig decreased, indicating that Lig’s therapeutic effect was related to the extent of mPTP opening.

Conclusion

The mitochondria-inflammation pathway plays a critical role in regulating migraine. Lig exerts anti-migraine effects primarily by modulating the mitochondria-inflammation pathway providing a novel perspective on migraine research that is beneficial for its clinical application.

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来源期刊

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

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