miR-126-5p通过靶向TRAF3抑制糖氧剥夺再灌注介导的HT22细胞凋亡和炎症

miR-126-5p Inhibits Oxygen-glucose Deprivation/Reperfusion Mediated Apoptosis and Inflammatory Response in HT22 Cells by Targeting TRAF3

目的探讨miR-126-5p通过靶向肿瘤坏死因子受体相关因子3(tumor necrosis factor receptor-associated factor 3,TRAF3)对糖氧剥夺再灌注(oxygen-glucose deprivation/reperfusion,OGD/R)介导的小鼠海马神经元细胞HT22细胞凋亡和炎症的影响。方法模拟缺血/再灌注损伤(ischemia/reperfusion,I/R)损伤在体外建立氧糖剥夺/复氧(oxygen-glucose deprivation/reperfusion,OGD/R)细胞模型,分析miR-126-5p与TRAF3靶向关系及对HT22细胞凋亡和炎症反应的影响。结果与对照组比较,OGD/R组中miR-126-5p下调而TRAF3 mRNA及蛋白水平上调,细胞存活率及Bcl-2蛋白水平降低,乳酸脱氢酶(lactate dehydrogenase,LDH)释放量、细胞凋亡率、Bax及Cleaved caspase-3蛋白水平升高(P均<0.05)。与OGD/R+mimic-NC组比较,OGD/R+miR-mimic组、OGD+miR-mimic+pcDNA组TRAF3蛋白水平、LDH释放量、细胞凋亡率、Bax及Cleaved caspase-3蛋白水平明显降低,细胞存活率及Bcl-2蛋白水平升高,而OGD+miR-mimic+pcDNA-TRAF3组各指标升高,细胞存活率明显下降(P均<0.05)。结论miR-126-5p通过靶向TRAF3,抑制OGD/R介导的HT22细胞凋亡和炎症反应,从而对神经元细胞发挥保护作用。

Objective To explore the effect of miR-126-5p on apoptosis and inflammatory response in mouse hippocampal neuron HT22 cells mediated by oxygen-glucose deprivation/reperfusion(OGD/R)by targeting tumor necrosis factor receptor-associated factor 3(TRAF3).Methods The OGD/R cell model was established in vitro by simulating ischemia/reperfusion(I/R)injury.The targeting relationship between miR-126-5p and TRAF3 and the effect of miR-126-5p on apoptosis and inflammatory response in HT22 cells were analyzed.Results The level of miR-126-5p in the OGD/R group was down-regulated while the mRNA and expression levels of TRAF3 were upregulated when compared with those in the control group.The cell survival rate and the Bcl-2 expression level in the OGD/R group were decreased while the lactate dehydrogenase(LDH)release,the apoptosis rate and the protein expression levels of Bax and cleaved caspase-3 in the OGD/R group were increased when compared with those in the control group(all P<0.05).The protein expression levels of TRAF3,Bax and cleaved caspase-3,the LDH release,the apoptosis rate were significantly decreased in the OGD/R+miR-mimic group and the OGD+miR-mimic+pcDNA group while the cell survival rate and the protein expression level of Bcl-2 were increased when compared with those in the OGD/R+mimic-NC group.In addition,the above indicators were elevated in the OGD+miR-mimic+pcDNA-TRAF3 group while the cell survival rate was significantly lowered when compared with those in the OGD/R+mimic-NC group(all P<0.05).Conclusion miR-126-5p can inhibit the OGD/R-mediated apoptosis of and inflammatory response in HT22 cells by targeting TRAF3,thus playing a protective role on neuronal cells.