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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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

Received: 18 September 2017

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	WU Xiushao
	WU Jing
	LIU Zixia
	CHEN Xujiao.

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https://xb.wmu.edu.cn/EN/ OR https://xb.wmu.edu.cn/EN/Y2018/V48/I3/202

[1] TUTTOLOMONDO A, SIMONETTA I, PINTO A. MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure[J]. Expert Opin Ther Targets, 2016, 20(11): 1287-1300.
[2] MORI S, GIBSON G, MCTIERNAN C F. Differential expression of MMPs and TIMPs in moderate and severe heart failure in a transgenic model[J]. J Card Fail, 2006, 12(4): 314-325.
[3] PEREZ-TERNERO C, WERNER C M, NICKEL A G, et al. Ferulic acid, a bioactive component of rice bran, improves oxidative stress and mitochondrial biogenesis and dynamics in mice and in human mononuclear cells[J]. J Nutr Biochem, 2017, 48: 51-61.
[4] RUKKUMANI R, PRIYANKA A, SANKAR P, et al. Ferulic acid influences hepatic expression pattern of matrix metalloproteinases during alcohol and PUFA induced toxicity[J]. Eur Rev Med Pharmacol Sci, 2012, 16(15): 2147-2153.
[5] ALAM M A, SERNIA C, BROWN L. Ferulic acid improves cardiovascular and kidney structure and function in hypertensive rats[J]. J Cardiovasc Pharmacol, 2013, 61(3): 240-249.
[6] MIR S A, CHATTERJEE A, MITRA A, et al. Inhibition of signal transducer and activator of transcription 3 (STAT3) attenuates interleukin-6 (IL-6)-induced collagen synthesis and resultant hypertrophy in rat heart[J]. J Biol Chem, 2012, 287(4): 2666-2677.
[7] XU J, CARRETERO O A, LIN C X, et al. Role of cardiac overexpression of ANG II in the regulation of cardiac function and remodeling postmyocardial infarction[J]. Am J Physiol Heart Circ Physiol, 2007, 293(3): H1900-1907.
[8] PERFILOVA V N, D’IAKOVA A V, TIURENKOV I N. Cardioprotective action of ferulic acid upon heart under stressor damage conditions[J]. Eksp Klin Farmakol, 2005, 68(5): 19-22.
[9] YOGEETA S K, GNANAPRAGASAM A, SENTHILKUMAR S, et al. Synergistic salubrious effect of ferulic acid and ascorbic acid on membrane-bound phosphatases and lysosomal hydrolases during experimental myocardial infarction in rats[J]. Life Sci, 2006, 80(3): 258-263.
[10] ZHANG X, LI W, SHEN P, et al. STAT3 Suppression is involved in the protective effect of SIRT6 against cardiomyocyte hypertrophy[J]. J Cardiovasc Pharmacol, 2016, 68(3): 204-214.
[11] KUNISADA K, NEGORO S, TONE E, et al. Signal transducer and activator of transcription 3 in the heart transduces not only a hypertrophic signal but a protective signal against doxorubicin-induced cardiomyopathy[J]. Proc Natl Acad Sci U S A, 2000, 97(1): 315-319.
[12] ZHANG W, QU X, CHEN B, et al. Critical roles of STAT3 in beta-adrenergic functions in the heart[J]. Circulation, 2016,
133(1): 48-61.
[13] TAGER T, WIEBALCK C, FROHLICH H, et al. Biological variation of extracellular matrix biomarkers in patients with stable chronic heart failure[J]. Clin Res Cardiol, 2017, 106 (12): 974-985.
[14] DELEON-PENNELL K Y, MESCHIARI C A, JUNG M,
et al. Matrix metalloproteinases in myocardial infarction and heart failure[J]. Prog Mol Biol Transl Sci, 2017, 147: 75-100.