Down-regulation of miR-34a-5p activates PINK1/Parkin pathway to mitigate neurological dysfunction in rats with intracerebral hemorrhage
10.13431/j.cnki.immunol.j.20250046
- VernacularTitle:miR-34a-5p下调激活PINK1/Parkin通路减轻脑出血大鼠神经功能障碍
- Author:
Yanpeng MA
1
;
Shao HAN
1
;
Jianbo LI
1
;
Xiaoheng GAO
1
;
Jingchuan GUO
1
;
Tao ZHOU
1
Author Information
1. 056002,邯郸市第一医院神经外三科
- Publication Type:Journal Article
- Keywords:
MicroRNA-34a-5p;
PTEN-induced kinase 1/Parkin pathway;
Intracerebral hemorrhage;
Neurological function
- From:
Immunological Journal
2025;41(5):305-311
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of microRNA(miR)-34a-5p on neurological function of rats with intracerebral hemorrhage(ICH)by adjusting PTEN-induced kinase 1(PINK1)/Parkin pathway.Methods SD rats were assigned into sham surgery group(Sham),ICH group,inhibitor NC group,miR-34a-5p inhibitor group,miR-34a-5p inhibitor+DMSO group,and miR-34a-5p inhibitor+Mdivi-1 group,with 8 rats in each group.Modified neurological severity score(mNSS)was used to assess changes in neurological function of rats;HE staining was used to observe the pathological changes in the brain tissue of rats;transmission electron microscopy was used to observe autophagy in brain tissue;TUNEL staining was used to observe cell apoptosis;qRT-PCR experiment was used to detect the mRNA levels of miR-34a-5p,PINK1 and Parkin in the brain tissues;Western blot experiments were used to measure PINK1,Parkin,Beclin1 and P62 proteins in the brain tissues of rats;dual luciferase reporter gene assay was used to determine the targeting relationship between miR-34a-5p and PINK1.Results Compared with the inhibitor NC group,the miR-34a-5p inhibitor group demonstrated lower levels of neuronal necrosis,red blood cell amount,inflammatory cell amount,autophagic vacuole amount,mNSS score,TUNEL positivity rate,miR-34a-5p expression and p62 protein,but higher levels of PINK1,Parkin mRNA and protein expression,and Beclin1 protein expression(P<0.05).Compared with the miR-34a-5p inhibitor+DMSO group,the changes mentioned above in rat of the miR-34a-5p inhibitor+Mdivi-1 group are all reversed(P<0.05).In the dual luciferase reporter gene experiment,the relative luciferase activity of cells in the miR-34a-5p mimic and PINK1-WT cotransfected group was greatly reduced(P<0.05).Conclusion The downregulation of miR-34a-5p may alleviate neurological dysfunction in ICH rats by adjusting PINK1/Parkin pathway.