Objective To investigate the role and mechanism of microRNA(miR)-4472 targeting PIN1 in regulating the nuclear factor kappa B(NF-κB)/signal transducer and activator of transcription 3(STAT3)signaling pathway in a rat model of hypoxic-ischemic encephalopathy(HIE).Methods Between January 2022 and January 2024,sixty Sprague-Dawley rats were randomly assigned to six groups at The Second Hospital of Jiaxing using a random number table method:a normal control group,an HIE model group,an inhibition control group,a miR-4472 inhibition group,a miR-4472 inhibition+interference control group,and a miR-4472 inhibition+PIN1 interference group,with ten rats in each group.There was no significant difference in body mass among the six groups(all P＞0.05).Rat models of HIE were established using the Rice-Vannucci method.Behavioral performance was assessed using the Morris water maze test,while neurological function was evaluated using the Longa scoring method.Apoptosis was detected using the TUNEL assay,and the expression of NF-κB and STAT3 protein was measured using Western blot analysis.Results Compared with the HIE model group,the miR-4472 inhibition group and the miR-4472 inhibition+interference control group showed a shortened escape latency,while the miR-4472 inhibition+PIN1 interference group exhibited an extended escape latency(all P＜0.05).The number of platform crossings in the miR-4472 inhibition+PIN1 interference group[(2.13±0.54)times]was significantly lower than that in the HIE model group[(3.56±0.71)times],the inhibition control group[(3.61±0.87)times],the miR-4472 inhibition group[(5.47±1.29)times],and the miR-4472 inhibition+interference control group[(5.58±1.32)times](t=5.07,4.57,7.55,7.65,all P＜0.05).The Longa score in the miR-4472 inhibition+PIN1 interference group[(3.03±0.30)points]was significantly lower than that in the HIE model group[(2.45±0.54)points],the inhibition control group[(2.38±0.69)points],the miR-4472 inhibition group[(1.27±0.46)points],and the miR-4472 inhibition+interference control group[(1.29±0.51)points](t=2.97,2.73,10.13,9.30,all P＜0.05).The apoptosis rate of hippocampal neurons in the miR-4472 inhibition+PIN1 interference group[(25.34±6.16)％]was significantly lower than that in the HIE model group[(18.42±5.46)％],the inhibition control group[(17.95±4.38)％],the miR-4472 inhibition group[(8.89±2.10)％],and the miR-4472 inhibition+interference control group[(9.13±2.57)％](t=2.97,2.73,10.13,9.30,all P＜0.05).Compared with the HIE model group,the miR-4472 inhibition group and the miR-4472 inhibition+interference control group exhibited decreased gray values of NF-κB and STAT3 protein,while the miR-4472 inhibition+PIN1 interference group showed increased gray values of NF-κB and STAT3 protein(all P＜0.05).Conclusion miR-4472 targets and regulates PIN1,which contributes to HIE injury through the activation of the NF-κB/STAT3 signaling pathway.
万方数据
维普
