小檗碱对大鼠压力超负荷肥厚心肌组织miR-21-3p表达的影响及其干预心肌肥厚的作用机制

Effect of berberine on the expression of miR-21-3p in hypertrophic myocardial tissue under pressure overload and the mechanism of inhibition for cardiac hypertrophy

目的探讨小檗碱对大鼠压力超负荷肥厚心肌组织miR-21-3p表达的影响及其干预心肌肥厚的作用机制。方法2019年6月—2020年9月于武汉科技大学实验动物中心进行实验。取SPF级雄性SD大鼠36只随机数字表法分为假手术组、模型组及小檗碱组,每组12只。模型组采用腹主动脉缩窄法构建心肌肥厚模型,小檗碱组在模型组基础上予以小檗碱灌胃处理,假手术组只暴露腹主动脉后关腹不做任何处理。40天后测量大鼠心脏超声指标,心、体质量及心体质量比,检测心肌组织中ANP、BNP及miR-21-3p表达,AKT、GSK3β及其磷酸化水平的表达。结果与假手术组比较,模型组大鼠左心室舒张末期后壁厚度(LVPWT)、心脏质量、心体质量比增加,左心室舒张末期内径(LVEDD)、左心室射血分数(LVEF)减少(P<0.05);与模型组比较,小檗碱组大鼠LVPWT、心脏质量、心体质量比减少,LVEDD、LVEF增加,差异均有统计学意义(t/P=2.864/0.021、3.929/0.004、3.866/0.005、4.518/0.002、2.841/0.022)。与假手术组比较,模型组大鼠心肌组织ANP、BNP、miR-21-3p、p-AKT及p-GSK3β表达上调(P<0.05);与模型组比较,小檗碱组上述心肌指标表达均下调,差异均有统计学意义(t/P=8.845/0.000、9.514/0.000、15.376/0.000、20.090/0.000、27.945/0.000)。结论在压力超负荷诱导的心肌肥厚大鼠模型中,小檗碱通过抑制miR-21-3p表达及AKT/GSK3β信号通路活性进而抑制心肌肥厚。

Objective To investigate the effect of berberine on the expression of miR-21-3p in hypertrophic myocardial tissue under pressure overload and the mechanism of inhibition for cardiac hypertrophy.Methods From June 2019 to September 2020,the experiments were conducted at the Laboratory Animal Center of Wuhan University of Science and Technology.A total of 36 male SPF SD rats were randomly divided into control group,model group and berberine group,with 12 rats in each group.In the model group,cardiac hypertrophy model was established by abdominal aortic constriction;the berberine group was given intragastric treatment on the basis of the model group,and the control group was not given any treatment.After 40 days,the cardiac ultrasonographic indexes of rats were measured.The expressions of ANP,BNP and miR-21-3p were detected by RT-qPCR.The expressions of Akt,GSK3βand their phosphorylation levels were detected by Western Blot.Results Compared with the control group,left ventricular end-diastolic posterior wall thickness(LVPWT),heart weight,heart weight ratio increased,left ventricular end-diastolic diameter(LVEDD)and left ventricular ejection fraction(LVEF)decreased in the model group and berberine group(P<0.05).Compared with the model group,LVPWT,heart weight,heart weight ratio,decreased,LVEDD and LVEF increased(t/P=2.864/0.021,3.929/0.004,3.866/0.005,4.518/0.002,2.841/0.022),and the expression levels of ANP,BNP,miR-21-3p,p-Akt and p-GSK3βwere down-regulated in berberine group(t/P=8.845/0.000,9.514/0.000,15.376/0.000,20.090/0.000,27.945/0.000).Conclusion In the rat model of cardiac hypertrophy induced by pressure overload,berberine can inhibit cardiac hypertrophy by inhibiting the expression of miR-21-3p and the activity of Akt/GSK3βsignaling pathway.