阿魏酸通过抑制STAT3蛋白活化调控慢性心力衰竭大鼠心肌MMP-1和TIMP-1的表达

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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、25 mg/kg阿魏酸组、50 mg/kg阿魏酸组和100 mg/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Western blot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Western blot检测心肌MMP-1和TIMP-1的mRNA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-1 mRNA和蛋白表达升高（P＜0.05），TIMP-1 mRNA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-1 mRNA和蛋白表达降低（P＜0.05），TIMP-1 mRNA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。

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关键词 ：阿魏酸, 慢性心力衰竭, 信号转导与转录激活因子-3, 基质金属蛋白酶-1, 大鼠

Abstract：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.

Key words： ferulic acid chronic heart failure signal transducer and activator transcription-3 matrix metalloproteinase-1 rats

收稿日期: 2017-09-18

基金资助:浙江省中医药基金资助项目（201518003）。

通讯作者: 陈旭娇，主任医师，硕士生导师，Email：chenxujiaozjhz@163.com。

作者简介: 吴秀绍（1989-），男，浙江苍南人，住院医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I3/202

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