在实验性糖尿病神经病变中，吲哚-3-丙酸通过调节 PERK-IRE1-ATF4-CHOP 信号，减轻高血糖诱导的 ER 应激反应并增强线粒体功能。

IF 2.5 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Archives of Physiology and Biochemistry Pub Date : 2024-06-01 Epub Date: 2022-01-11 DOI:10.1080/13813455.2021.2024577

Chayanika Gundu, Vijay Kumar Arruri, Bhoomika Sherkhane, Dharmendra Kumar Khatri, Shashi Bala Singh

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引用次数: 0

摘要

研究目的我们旨在评估吲哚-3-丙酸（IPA）对链脲佐菌素（STZ）诱导的大鼠糖尿病周围神经病变（DPN）以及高糖（HG）诱导的神经2a（N2A）细胞神经毒性的神经保护作用：方法：雄性 SD 大鼠经 STZ（55 毫克/千克，静脉注射）和 IPA（10 和 20 毫克/千克，口服）诱导糖尿病，从糖尿病诱导后第六周开始连续两周给药。对坐骨神经、DRGs和N2A细胞进行了神经行为和功能评估，并进行了各种分子研究，以评估IPA对HG诱导的坐骨神经、DRGs和N2A细胞ER应激和线粒体功能障碍的影响：结果：糖尿病大鼠和暴露于高血糖的 N2A 细胞的氧化损伤明显增加，同时伴有 ER 应激和线粒体功能障碍，以及凋亡标志物增加。持续两周的 IPA 治疗明显缓解了这些变化，并减轻了疼痛行为：IPA对高血糖损伤具有神经保护活性。

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Indole-3-propionic acid attenuates high glucose induced ER stress response and augments mitochondrial function by modulating PERK-IRE1-ATF4-CHOP signalling in experimental diabetic neuropathy.

Objectives: We aimed to evaluate the neuroprotective effect of Indole-3-propionic acid (IPA) against streptozotocin (STZ) induced diabetic peripheral neuropathy (DPN) in rats and in high glucose (HG) induced neurotoxicity in neuro2a (N2A) cells.

Methods: Diabetes was induced in male SD rats STZ (55 mg/kg, i.p.) and IPA (10 and 20 mg/kg, p.o.) was administered for two weeks, starting from sixth week after diabetes induction. Neurobehavioral, functional assessments were made, and various molecular studies were performed to evaluate the effect of IPA on HG induced ER stress and mitochondrial dysfunction in sciatic nerves, DRGs and in N2A cells.

Results: Diabetic rats and high glucose exposed N2A cells showed marked increase in oxidative damage accompanied by ER stress and mitochondrial dysfunction along with increased apoptotic markers. IPA treatment for two weeks markedly alleviated these changes and attenuated pain behaviour.

Conclusion: IPA exhibited neuroprotective activity against hyperglycaemic insults.

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来源期刊

Archives of Physiology and Biochemistry ENDOCRINOLOGY & METABOLISM-PHYSIOLOGY

CiteScore

6.90

自引率

3.30%

发文量

期刊介绍： Archives of Physiology and Biochemistry: The Journal of Metabolic Diseases is an international peer-reviewed journal which has been relaunched to meet the increasing demand for integrated publication on molecular, biochemical and cellular aspects of metabolic diseases, as well as clinical and therapeutic strategies for their treatment. It publishes full-length original articles, rapid papers, reviews and mini-reviews on selected topics. It is the overall goal of the journal to disseminate novel approaches to an improved understanding of major metabolic disorders. The scope encompasses all topics related to the molecular and cellular pathophysiology of metabolic diseases like obesity, type 2 diabetes and the metabolic syndrome, and their associated complications. Clinical studies are considered as an integral part of the Journal and should be related to one of the following topics: -Dysregulation of hormone receptors and signal transduction -Contribution of gene variants and gene regulatory processes -Impairment of intermediary metabolism at the cellular level -Secretion and metabolism of peptides and other factors that mediate cellular crosstalk -Therapeutic strategies for managing metabolic diseases Special issues dedicated to topics in the field will be published regularly.