MiR-146b诱导小鼠主动脉夹层发生机制的实验研究

MiR-146b induces aortic dissection by regulating HIPPO-YAP pathway and apoptosis of vascular wall cells

目的:探究微小RNA-146b(miR-146b)诱导小鼠主动脉夹层(AD)的机制。方法:将小鼠随机分为3组:对照组、AD组和抑制剂(Antagomir)组,每组12只。通过喂养β-氨基丙腈建立AD模型,通过尾静脉注射miR-146b抑制剂干预小鼠。干预后采集各组主动脉样本,测量主动脉直径(LD)、中膜厚度(MT)。检测各组主动脉miR-146b水平、凋亡相关蛋白水平以及HIPPO-YAP通路相关指标。结果:对照组未出现AD;AD组AD发生率为75.00%(9/12),显著高于对照组;Antagomir组AD发生率33.00%(3/12),显著低于AD组。与对照组比较,AD组MT降低而LD升高,Antagomir组MT显著高于AD组而LD显著低于对照组。与对照组比较,AD组miR-146b水平显著高于对照组,Antagomir组miR-146b水平显著低于对照组。与对照组比较,AD组Caspase3和Bax显著升高而Bcl-2显著降低,Antagomir组Caspase3和Bax低于AD组而Bcl-2高于AD组。AD组p-LATS1/LATS1和p-YAP/YAP水平显著高于对照组,Antagomir组p-LATS1/LATS1和p-YAP/YAP显著低于AD组。结论:miR-146b可能通过调节HIPPO-YAP通路促进血管壁细胞凋亡参与小鼠AD形成。

Objective:To explore the mechanism by which microRNA(miR)-146b induces aortic dissection(AD)by regulating HIPPO-YAP pathway and apoptosis of vascular wall cells.Methods:Mice were randomized into 3 groups:control group,AD group and antagomir group.The AD model was established by feedingβ-aminopropionitrile and the mice were intervened by tail veininjection of miR-146b antagomir.After the intervention,the aortic samples of each group were collected,and the aortic tissue was observed by Hematoxylin-eosin(HE)and the aortic diameter(LD)and media thickness(MT)were measured.The miR-146b,apoptosis-related proteins,and HIPPO-YAP pathways in each group of aorta were detected and compared.Results:There were 9 cases of AD in the AD group,the incidence rate was 75.00%(9 cases),which was significantly higher than the control group.The incidence of AD in the Antagomir group was 33.00%(3 cases),which was significantly lower than that in the AD group.Compared with the control group,HE staining results showed that the MT of the AD group decreased and the LD increased.The MT of the antagomir group was significantly higher than that of the AD group and the LD was significantly lower than that of the control group.Compared with the control group,the level of miR-146b in the AD group was significantly higher than that in the control group.The level of miR-146b in the antagomir group was significantly lower than that in the control group.Compared with the control group,Caspase3 and Bax were significantly increased and Bcl-2 was significantly decreased in the AD group.And Caspase3 and Bax in the antagomir group were lower than those in the AD group and Bcl-2 was higher than the AD group.The levels of p-LATS1/LATS1 and p-YAP/YAP in the AD group were significantly higher than those in the control group.The p-LATS1/LATS1 and p-YAP/YAP in the antagomir group were significantly lower in the AD group.Conclusion:In AD mice,inhibition of miR-146b inhibits apoptosis by reducing phosphorylation of LATS1 and YAP proteins in the Hippo pathway,suggesting that miR-146b may participate in AD through the Hippo pathway promoting VSMC apoptosis.