摘要
目的:探索阿魏酸是否可以通过抑制信号转导与转录激活因子-3(STAT3)蛋白活化调控慢性心力衰竭(CHF)大鼠心肌基质金属蛋白酶-1(MMP-1)和基质金属蛋白酶特异性抑制物-1(TIMP-1)的表达。方法:将50只SD大鼠随机分为假手术组、模型组、25mg/kg阿魏酸组、50mg/kg阿魏酸组和100mg/kg阿魏酸组,每组10只。冠脉结扎法制作CHF模型。手术8周后行超声心动图检测心功能变化;Masson染色观察胶原变化;采用Westernblot检测心肌组织中p-STAT3的蛋白表达水平;取左心室心肌,用RT-PCR和Westernblot检测心肌MMP-1和TIMP-1的m RNA和蛋白的表达变化。结果:与假手术组相比,模型组左室收缩末期内径及舒张末期内径增大(P<0.05),射血分数降低(P<0.05),心肌组织中胶原沉积明显,p-STAT3蛋白表达升高(P<0.05),MMP-1m RNA和蛋白表达升高(P<0.05),TIMP-1m RNA和蛋白表达降低(P<0.05);与模型组相比,不同浓度阿魏酸干预后,CHF大鼠左室收缩末期内径及舒张末期内径减少(P<0.05),射血分数升高(P<0.05),心肌组织中胶原沉积减少,p-STAT3蛋白表达降低(P<0.05),MMP-1m RNA和蛋白表达降低(P<0.05),TIMP-1m RNA和蛋白表达升高(P<0.05)。结论:阿魏酸可能通过降低STAT3蛋白活化调控CHF大鼠心肌组织MMP-1和TIMP-1表达,延缓CHF进展。
Objective:To investigate whether ferulic acid could regulate the expression of matrix metalloproteinase-1(MMP-1)and matrix metalloproteinase specific inhibitor-1(TIMP-1)in myocardium of rats with chronic heart failure by inhibiting the activation of STAT3 protein.Methods:Fifty SD rats were randomly divided into 5 groups,sham operation group,model group,25 mg/kg ferulic acid group,50 mg/kg ferulic acid group and 100 mg/kg ferulic acid group.A rat model of chronic heart failure was made by coarctation of aorta.After 8 weeks of surgery,echocardiographic assessment was performed to detect the changes of cardiac function;collagen changes with Masson staining were observated;the expression of p-STAT3 protein level was detected by Western blot in myocardial tissue;the left ventricular myocardial expression of MMP-1 and TIMP-1 mRNA and protein were detected by RT-PCR and Western blot.Results:Compared with sham operation group in the model group,left ventricular end systolic diameter and left ventricular end diastolic diameter increased(P<0.05),ejection fraction decreased(P<0.05),myocardial collagen deposition obviously,the expression of p-STAT3 protein increased(P<0.05),expression of MMP-1 mRNA and protein increased(P<0.05),TIMP-1 mRNA and protein decreased(P<0.05).Compared with the model group,in the ferulic acid groups,left ventricular end systolic diameter and left ventricular end diastolic diameter reduced(P<0.05),ejection fraction increased(P<0.05),collagen deposition in the myocardial tissue decreased(P<0.05),p-STAT3 protein expression decreased(P<0.05),MMP-1 mRNA and protein expression decreased(P<0.05),TIMP-1 mRNA and protein increased(P<0.05).Conclusion:Ferulic acid may delay the progression of chronic heart failure by regulating the expression of MMP-1 and TIMP-1 in cardiac tissue of rats with chronic heart failure by decreasing the activation of STAT3 protein.
作者
吴秀绍
吴竞
刘子夏
陈旭娇
WU Xiushao;WU Jing;LIU Zixia;CHEN Xujiao(Department of Geriatrics,Zhejiang Hospital,Hangzhou,310000;Department of Oncology,Zhejiang Hospital,Hangzhou,310000)
出处
《温州医科大学学报》
CAS
2018年第3期202-206,共5页
Journal of Wenzhou Medical University
基金
浙江省中医药基金资助项目(201518003)
