吲哚丙酸通过调节实验性糖尿病神经病变中 PERK-IRE1-ATF4-CHOP 信号通路减轻高糖诱导的内质网应激反应并增强线粒体功能。
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.
机构信息
Molecular and Cellular Neuroscience Laboratory, Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Hyderabad, Balanagar, India.
Department of Neurosurgery, University of Wisconsin-Madison, Madison, WI, USA.
出版信息
Arch Physiol Biochem. 2024 Jun;130(3):243-256. doi: 10.1080/13813455.2021.2024577. Epub 2022 Jan 11.
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, ) and IPA (10 and 20 mg/kg, ) 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.
目的
本研究旨在评估吲哚丙酸（IPA）对链脲佐菌素（STZ）诱导的糖尿病周围神经病变（DPN）大鼠和高葡萄糖（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（55mg/kg）诱导糖尿病，从糖尿病诱导后第 6 周开始，IPA（10 和 20mg/kg）连续给药 2 周。进行神经行为和功能评估，并进行各种分子研究，以评估 IPA 对 HG 诱导的坐骨神经、背根神经节和 N2A 细胞内质网应激和线粒体功能障碍的影响。
结果
糖尿病大鼠和高葡萄糖暴露的 N2A 细胞表现出明显的氧化损伤增加，伴有内质网应激和线粒体功能障碍，以及凋亡标志物增加。IPA 治疗 2 周可显著减轻这些变化，并减轻疼痛行为。
结论
IPA 对高血糖损伤表现出神经保护活性。
Zotero 插件