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| Protective effect of metformin against myocardial injury in septic rats |
| Ai Bo, Li Wen-qiang |
| Department of Emergency, Remin Hospital of Wuhan University, Wuhan 430060, China |
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Abstract Objective Rat sepsis model was made by cecal ligation and puncture(CLP) technique in order to observe the treatment of metformin on myocardial injury in septic rats and to explore its potential mechanism. Methods 60 male Wistar rats were divided into four groups randomly: Sham group, Sham/M group, CLP, CLP/M group. Each group was divided into 12, 24 h observation subgroups. Sham group was only opened the abdomen to take out the appendix, then turned back into the abdominal cavity without ligation and perforation. Sham/M group animals were administered with metformin (100 mg/kg) in lavage way 1.5 h before operation, and the others were the same as the Sham group. The CLP group was sepsis model by CLP technique. CLP/M group animals were administered with metformin (100 mg/kg) in lavage way 1.5 h before operation, and the others were the same as the CLP group. Blood level of ALT, AST, Cr was detected in each group at the observation time point respectively; ELISA was used to detect serum TNF-α, IL-1β, cTnI expression level; TUNEL method was used to detect myocardial cell apoptosis. Results ①At 12, 24 h, the Sham group and Sham/M group rats did not show obvious differences in serum ALT, AST, Cr, TNF-α, IL-1β, cTnI levels (P>0.05); compared with the control group, the serum ALT, AST, Cr levels in CLP group and CLP/M group rats increased significantly (P<0.01); at the same time, the CLP/M group level decreased significantly compared with the CLP group(P<0.01). ②The Sham group(2.71%) and Sham/M group(2.81%) did not show obvious difference in myocardial cells AI value (P>0.05); The myocardial cells AI value increased obviously in CLP group(21.28%) compared with the Sham group(P<0. 01); and AI value in CLP/M group(16.8%) decreased significantly compared with the CLP group(P<0.01). Conclusion Metformin has significant protective effect against myocardial injury in CLP model rats.
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Corresponding Authors:
Li Wen-qiang, E-mail: 1292110424@qq.com
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| ［1］Merx MW， Weber C. Sepsis and the heart［J］. Circulation， 2007， 116(7): 793 －802．
［2］艾波，李文强.脓毒症心肌损伤机制的研究进展［J］.职业与健康， 2017， 33（3）：425-429.
［3］Oyama J, Blais C Jr, Liu X， et al. Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice［J］. Circulation， 2004， 109（6):784-789.
［4］Soraya H, Clanachan AS, Rameshrad M, et al. Chronic treatment with metformin suppresses toll-like receptor 4 signaling and attenuates left ventricular dysfunction following myocardial infarction. Eur［J］. Pharmacol, 2014, 737: 77-84.
［5］Caballero AE， Delgado A， Aguilar-Salinas CA， et al. The differential effects of metformin on markers of endothelial activation and inflammation in subjects with impaired glucose tolerance: a placebo-controlled, randomized clinical trial［J］. J Clin Endocrinol Metab， 2004， 89(8):3943-3948.
［6］Haleh V， Maryam R， Moslem N， et al. Cardioprotective effect of metformin in lipopolysaccharide-induced sepsis via suppression of toll-like receptor 4 (TLR4) in heart［J］. Europ J Pharmacol， 2016， 772: 115-123.
［7］Eiseman B, Sloan R, Hansbrough J， et al. Multiple organ failure: clinical and experimental［J］. Am Surg, 1980， 46 (1): 14-19.
［8］Meldrum DR. Tumor necrosis factor in the heart［J］. Am J Physiol, 1998, 274(3Pt 2):R577-R595.
［9］Hochstadt A， Meroz Y， Landesberg G. Myocardial dysfunction severe sepsis and septic shock:morequestions than answers［J］.J Cardiothorac Vasc Anesth， 2011， 25(3):526-535.
［10］Lancel S， Joulin O， Favory R， et al． Ventricular myocyte caspases are directly responsible for endotoxin-induced cardiac dys-function［J］. Circulation， 2005， 111(20):2596-2604．
［11］Fu YN， Xiao H， Ma XW， et al． Metformin attenuates pressure overload-induced cardiac hypertrophy via AMPK activation［J］. Acta Pharmacol Sin， 2011， 32（7）:879-887．
［12］Barreto-Torres G， Parodi-Rullán R， Javadov S.The role of PPRα in metformin-induced attenuation of mitochondrial dysfunction in acute cardiac ischemia/reperfusion in rats［J］． Int J Mol Sci, 2012, 13（6）：7694-7709．
［13］Kobashigawa LC， Xu YC， Padbury JF， et al． Metformin rotects cardiomyocyte from doxorubicin induced cytotoxicity through an AMP-activated protein kinase dependent signaling pathway:an in vitro study［J］． PLoS One， 2014， 9(8):e104 888．
［14］Kewalramani G， Puthanveetil P， Wang F， et al． AMP-activated protein kinase confers protection against TNF-α-induced cardiac cell death［J］. Cardiovasc Res， 2009， 84(1):42-53． |
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