昆明医科大学学报2025，Vol.46Issue(9)：45-53,9.DOI:10.12259/j.issn.2095-610X.S20250905
大车前苷通过促进PINK1/Parkin线粒体自噬途径改善糖尿病周围神经病变的机制
Mechanistic Studies on the Improvement of Diabetic Peripheral Neuropathy by Plantamajoside via Promoting the PINK1/Parkin Mitochondrial Autophagy Pathway
摘要
Abstract
Objective To investigate the efficacy of plantamajoside(PMS)on diabetic peripheral neuropathy(DPN)and to explore its mechanism of action from mitochondrial autophagy.Methods Mice(C57BL/6J)were randomly divided into 6 groups(n=10):normal group(Control),model group(Model),positive drug group(LA),and low(L-PMS),medium(M-PMS),and high(H-PMS)dosage groups.High-sugar and high-fat diet with intraperitoneal injection of streptozotocin was used to duplicate the DPN model.After successful model duplication,the intervention was administered by gavage for 4 weeks.Sciatic nerve was taken,and pathological changes were observed by HE and Nissl staining;oxidative stress indexes SOD,MDA,GSH-Px and inflammatory factors such as IL-1β,IL-6,TNF-αin sciatic nerve tissues were detected by kits,and the expression of VDAC1,TOM20,COX IV,PINK1,Parkin,and autophagy proteins of Beclin1,LC3,P62 in mouse sciatic nerves was detected by Western blotting.Results PMS dose-dependently improved the behavioral indexes of DPN mice,reduced the pathological damage of sciatic nerve,and resulted in tightly arranged sciatic nerve fibers,clearly visible myelin structure,uniform coloration,and increased number of Schwann cells as well as Nissl bodies.Compared with the model group,both the M-PMS group and the H-PMS group increased the expression levels of SOD and GSH-Px(P<0.05),while decreased the expression of MDA(P<0.05);the M-PMS group and the H-PMS groups reduced the expression of IL-1β,IL-6,and TNF-α(P<0.05);the L-PMS group,M-PMS group,and H-PMS group reduced the expression levels of VDAC1,TOM20,and COX IV proteins(P<0.05);the L-PMS group,M-PMS group,and H-PMS group could differentially increase the expression of PINK1,Beclin1,Parkin,and LC3 proteins(P<0.05),and decrease the expression of P62 proteins(P<0.05).Conclusion PMS can play a role in ameliorating neurological injury in DPN mice by promoting PINK1/Parkin pathway-mediated mitochondrial autophagy and alleviating oxidative stress-related inflammatory injury.关键词
糖尿病周围神经病变/大车前苷/线粒体自噬/PINK1/Parkin/坐骨神经Key words
Diabetic peripheral neuropathy/Plantamajoside/Mitochondrial autophagy/PINK1/Parkin/Sciatic nerve分类
医药卫生引用本文复制引用
张晓霞,党浩源,番明谣,裴环,赵杰,崔换天,海青山..大车前苷通过促进PINK1/Parkin线粒体自噬途径改善糖尿病周围神经病变的机制[J].昆明医科大学学报,2025,46(9):45-53,9.基金项目
云南省科技厅应用基础研究基金(202101AZ070001-213) （202101AZ070001-213）
云南省中西医结合慢病防治重点实验室开放基金资助项目(CWCD2023-012) （CWCD2023-012）
云南省科技厅应用基础研究基金(202101AZ070001-064). （202101AZ070001-064）
