微小RNA-92a在支架内再狭窄患者的表达及其对血管平滑肌细胞增殖、迁移的影响

Expression of microRNA-92a in patients with in-stent restenosis and its effect on proliferation and migration of vascular smooth muscle cells

目的探讨微小RNA-92a(miR-92a)在支架内再狭窄(ISR)患者的表达以及对血管平滑肌细胞(VSMC)增殖、迁移的影响。方法行经皮冠状动脉介入术的冠心病患者60例分为ISR组(有ISR,30例)和非ISR组(无ISR,30例),同时选取30例非冠心病患者作为对照组。采用定量逆转录PCR检测外周血单个核细胞(PBMC)中miR-92a表达。将miR-92a模拟物(A组)、miR-92a抑制剂(B组)和miR-92a模拟物对照(C组)转染到人主动脉VSMC,同时取空白孔作为对照(D组)。采用CCK-8实验检测VSMC增殖,Transwell实验检测VSMC迁移,Western blot法检测VSMC和PBMC Krüppel样因子4(KLF4)蛋白表达。结果ISR组PBMC中的miR-92a表达高于非ISR组和对照组(P<0.05),非ISR组亦高于对照组(P<0.05)。A组细胞增殖和迁移较C组增多(P<0.01),而B组细胞增殖和迁移较D组减少(P<0.05)。ISR组PBMC中KLF4蛋白表达低于非ISR组和对照组(P<0.05)。A组KLF4蛋白表达低于C组(P<0.05),B组KLF4蛋白表达高于D组(P<0.05)。结论miR-92a在ISR患者PBMC中表达升高,miR-92a高表达能促进VSMC的增殖和迁移,可能是通过抑制KLF4的表达来实现的。

Objective To investigate the expression of microRNA-92 a(miR-92 a)in the patients with in-stent restenosis(ISR)and its effect on the proliferation and migration of vascular smooth muscle cells(VSMC).Methods The expression of miR-92 a was detected by quantitative reverse transcription PCR in peripheral blood mononuclear cell(PBMC)in 30 patients with ISR(group ISR),30 patients without ISR(group NISR)and 30 patients without coronary heart disease(control group).The miR-92 a mimics(group A),miR-92 a inhibitor(group B)and miR-92 a mimics control(group C)were transfected into human aortic VSMC.The blank wells were taken as the controls(group D).The VSMC proliferation and migration were detected by CCK-8 assay and Transwell experiment,respectively.The protein expression of Krüppel-like factor 4(KLF4)was detected of VSMC and PBMC by Western blot.Results The expression of miR-92 a in group ISR was higher than that in group NISR and control group(P<0.05),which was higher in group NISR than that in control group(P<0.05).The cell proliferation and migration were more in group A than those in group C(P<0.01),which were more in group D than those in group B(P<0.05).The protein expression of KLF4 was lower in group ISR than those in group NISR and control group(P<0.05).The protein expression of KLF4 was lower in group A than that in group C(P<0.05),which was higher in group B than that in group D(P<0.05).Conclusion The expression of miR-92 a is increased in PBMC of ISR patients.The high expression of miR-92 a can promote the proliferation and migration of VSMC,which may be achieved by inhibiting the expression of KLF4.