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| Experimental Study of Inhibited Myocardial Fibrosis by Liraglutide Following Acute Myocardial Infarction in Rats |
| QIAO Huiying, et al |
| Wujiang Hospital Affiliated to Nangtong University, Jiangsu Suzhou 215200, China |
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Abstract Objective: To investigate the effects of Liraglutide on myocardial fibrosis in rats after acute myocardial infarction (AMI). Methods: The rat model of AMI was established by occlusion of the left anterior descending artery. The AMI rats were randomly divided into 3 groups: Control group (n=6), Low dose liraglutide (LS) group (n=6, 0.09mg·kg-1·d-1) and high dose liraglutide (HS) group (n=6, 0.18mg·kg-1·d-1). Sham operation group (n=6), rats received normal saline. 4 weeks later, cardiac structure and function were assessed by echocardiography; collagen volume fraction was calculated by Sirius-redstaining; the apoptotic myocardial cells were detected by TUNEL method; Pro caspase3, cleaved caspase3, PARP, TGF-β and MMP-9 were determined by Western blotting. Results: Compared with Sham operation group, control group showed decreased LVEF, LVFS and increased LVEDd, LVESd (P<0.05). Compared with control group, LS group and HS group had obviously increased LVEF, LVFS and decreased LVEDd, LVESd (P<0.05). Collagen volume fraction and apoptotic index were significantly decreased in LS group and HS group when compared with control group (P<0.05). The expression of Pro caspase3, cleaved caspase3, PARP, TGF-β and MMP-9 were significantly decreased in LS group and HS group in compared with control group (P<0.05). Conclusion: Liraglutide can reduce myocardial fibrosis in rats after AMI which partly contributes to attenuate the expression of TGF-β and MMP-9 and reduce myocardial cell apoptosis.
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[1] Thygesen K, Alpert JS, White HD, et al. Universal definition of myocardial infarction [J]. Circulation, 2007, 116(22):2634~2653.
[2] Perez-Riera AR, Barbosa-Barros R, Shenasa M. Electrocardiographic markers of sudden cardiac death (including left ventricular hypertrophy) [J]. Card Electrophysiol Clin, 2017, 9(4):605~629.
[3] Pujadas G, Drucker DJ. Vascular biology of glucagon receptor superfamily peptides: mechanistic and clinical relevance [J]. Endocr Rev, 2016, 37(6):554~583.
[4] Chen WR, Chen YD, Tian F, et al. Effects of liraglutide on reperfusion injury in patients with ST-segment-elevation myocardial infarction [J]. Circ Cardiovasc Imaging, 2016, 9(12). pii: e005146.
[5] KristensenJ, MortensenUM, SchmidtM, et al. Lack of cardioprotection from subcutaneously and preischemic administered liraglutide in a closed chest porcine ischemia reperfusion model [J].BMC Cardiovasc Disord, 2009, 9:31.
[6] 卢慧芳,方义杰,李玥,等. 利拉鲁肽对急性心肌梗死大鼠血管新生和心肌保护的影响及机制研究[J].中国循环杂志,2017,32(11):1117~1122.
[7] Liao P, Yang D, Liu D,et al. GLP-1 and ghrelin attenuate high glucose/High lipid-induced apoptosis and senescence of human microvascular endothelial cells[J]. Cell Physiol Biochem, 2017, 44(5):1842~1855.
[8] Bisgaard LS, Bosteen MH, Fink LN, et al. Liraglutide reduces both atherosclerosis and kidney inflammation in moderately uremic LDLr-/- mice [J]. PLoS One, 2016, 11(12):e0168396.
[9] Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes [J]. N Engl Med, 2016, 375(4):311~322.
[10] Ipp E, Genter P, Childress K. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes [J]. N Engl Med, 2017, 376(9):890~891.
[11] De Mesquita FC, Guixé-Muntet S, Fernández-Iglesias A, et al. Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies [J]. Sci Rep, 2017, 7(1):3255.
[12] 刘美,苟思,陈海涛,等.胰高血糖素样肽-1对博莱霉素诱导的小鼠肺纤维化的作用及机制探讨[J].四川大学学报(医学版),2017,48(4):509~514.
[13] Kyhl K, Lonborg J, Hartmann B, et al. Lack of effect of prolonged treatment with liraglutide on cardiac remodeling in rats after acute myocardial infarction[J]. Peptides, 2017, 93:1~12. |
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2018, Vol. 24 
