miR-125a-5p attenuates neurological dysfunction and inflammatory responses in pentylenetetrazole-induced epileptic rats by targeting STAT3
10.3969/j.issn.1000-484X.2024.07.005
- VernacularTitle:miR-125a-5p通过靶向STAT3减轻戊四唑诱导的癫痫大鼠神经功能障碍和炎症反应
- Author:
Ping SHAN
1
;
Jilong ZHANG
Author Information
1. 武汉市第一医院,武汉 430022
- Keywords:
miR-125a-5p;
Signal transducer and activator of transcription 3;
Pentylenetetrazole;
Epilepsy;
Neurological dysfunction;
Inflammation
- From:
Chinese Journal of Immunology
2024;40(7):1373-1380
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the impacts of miR-125a-5p on neurological dysfunction and inflammatory response in pentylenetetrazole(PTZ)-induced epileptic rats by targeting signal transducer and activator of transcription 3(STAT3).Methods:Rats epilepsy models were established by PTZ ignition method and randomly grouped into six groups:Con group,PTZ group,PTZ+agomir NC group,PTZ+miR-125a-5p agomir group,PTZ+miR-125a-5p agomir+pcDNA group and PTZ+miR-125a-5p agomir+pc-STAT3 group.Impacts of miR-125a-5p on epilepsy duration,latency,number and severity of seizures in rats were evaluated.qRT-PCR was applied to detect miR-125a-5p and STAT3 mRNA expressions;Modified Nervous System Severity Score(mNSS),open field test and Rotarod test were applied to evaluate neurological function in epileptic rats;Morris water maze test was applied to evaluate cognitive function of epileptic rats;immunostaining was applied to observe neuronal apoptosis in hippocampal CA1 and CA3 regions;ELISA was applied to detect levels of inflammatory factors(TNF-α,IL-6,IL-1β and IL-18)in hippocampus;Western blot was applied to detect STAT3 protein expression in hippocampus;dual-luciferase assay was applied to verify the relationship between miR-125a-5p and STAT3.Results:In PTZ-induced epilepsy rats,expression of miR-125a-5p was up-regulated,while expression of STAT3 was down-regulated,and miR-125a-5p was targeted and inhibited expression of STAT3.Compared with PTZ group,PTZ+miR-125a-5p agomir group had shorter latency,lower epilepsy score,fewer seizure duration and times,lower mNSS,increased fall latency and movement distance in peripheral areas and total open area,greatly decreased escape latency,increased number of platform crossings and time spent in the target quadrant and swimming distance,reduced expressions of TNF-α,IL-6,IL-1β,IL-18 in hippocampus,and increased NenN+cells in CA3 and CA1 regions(P<0.05);overexpression of STAT3 could reverse the alleviating effects of miR-125a-5p agomir on neurological dysfunction and inflammatory response in epileptic rats(P<0.05).Conclusion:miR-125a-5p attenu-ates neurological dysfunction and inflammatory response in PTZ-induced epilepsy rats by targeting down-regulation of STAT3.
