Novel compound HYY-002 inhibits paroxysmal atrial fibrillation in rats

doi:10.12092/j.issn.1009-2501.2019.12.005

Abstract

Abstract:

AIM:To investigate the inhibitory effect of HYY-002 on atrial fibrillation(AF). METHODS:Male SD rats were randomized into 5 groups:normal,model,amiodarone(30 mg/kg,i.p.), low-dose and high-dose HYY-002 group. The rats were administrated Ach-CaCl2 (i.v.) for 10 days to establish rat AF model. From the 4th day, rats in treatment group were treated with amiodarone (30 mg/kg, i.p.) and HYY-002 (2 mg/kg, 10 mg/kg, i.g.) 1 hour before modeling. AF duration and ECG parameters were measured every day. On the 11th day, AERP of every rat were measured and the inflammatory cytokines and miR-135a in plasma were detected. RESULTS:In the model group, AF duration increased persistently and AERP shortened distinctly compared with normal group ［(61.83±4.13) vs. (72.70±7.05) ms, P<0.05］. The expression of TNF-α, IL-1 and IL-6 in plasma of model group were higher than normal group (P<0.05). High dose of HYY-002 (10 mg/kg) shortened AF duration effectively ［(6.42±1.38) vs. (16.32±1.31) s，P<0.01 vs. model group］, relieved the shortening of AERP induced by AF ［(77.78±3.79) vs. (61.83±4.13) ms, P<0.01 vs. model group］ and lowered the inflammatory cytokines level in plasma. Compared with normal group, the expression of miR-135a in plasma of model group was down-regulated obviously (P<0.01). CONCLUSION: HYY-002 has a significant therapeutic effect on AF, and miR-135a might be involved in the development of AF.

Key words: bradycardia, paroxysmal atrial fibrillation, inflammation, miR-135a

CLC Number:

R965.2

YANG Leixi, FENG Kai, FAN Xueting, WEI Yanchun, LIU Tingting, TANG Yiqun. Novel compound HYY-002 inhibits paroxysmal atrial fibrillation in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(12): 1347-1352.

References

［1］范卫东. 地尔硫卓治疗窦性心动过缓并阵发性心房颤动［J］. 中国基层医药, 2003, (12): 16-17.
［2］Miyazawa K, Lip GYH. Atrial fibrillation［J］. Medicine, 2018, 46(10): 627-631.
［3］Horie N, Kaminogo M, Izumo T, et al. Cilostazol may prevent cardioembolic stroke in patients undergoing antiplatelet therapy［J］. Neurol Res, 2015, 37(7): 619-623.
［4］陈春林, 巩甜甜, 汤依群, 等. SD大鼠房颤模型的建立［J］. 实验动物科学, 2009, 26(3): 1-4.
［5］汤依群, 孙书娟, 尹月淼, 等. 阵发性房颤诱发大鼠心房肌电重构特征研究［J］.中国临床药理学与治疗学, 2011, 16(11): 1205-1209.
［6］Alizade E, Sahin M, Simsek Z, et al. Cilostazol decreases total atrial conduction time in patients with peripheral artery disease［J］. Perfusion, 2014, 29(3): 265-271.
［7］Ishikawa T, Ohno S, Murakami T, et al. Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction［J］. Heart Rhythm, 2017, 14(5): 717-724.
［8］Amasyali B, Kilic A, Kilit C. Sinus node dysfunction and atrial fibrillation: Which one dominates［J］? Int J Cardiol, 2014, 175(2): 379-380.
［9］Kose S,Amasyali B,Kursaklioglu H,et al.Permanent junctional reciprocating tachycardia:An unusual presentation［J］. Int J Clin Pract,2009,63:518-521.
［10］Hada M, Miyazaki S, Kajiyama T, et al. Catheter ablation of paroxysmal atrial fibrillation in patients with sick sinus syndrome［J］. Heart Vessels, 2018, 34(3): 503-508.
［11］Cervenec RM, Stauthammer CD, Fine DM, et al. Survival time with pacemaker implantation for dogs diagnosed with persistent atrial standstill［J］. J Veter Cardiol, 2017, 19(3): 240-246.
［12］陈刚, 杨劲, 张广钦. 华法林与胺碘酮相互作用研究进展［J］. 中国临床药理学与治疗学, 2017, 22(2): 215-221.
［13］Sardar MR, Saeed W, Kowey PR. Antiarrhythmic drug therapy for atrial fibrillation［J］. Heart Fail Clin, 2016, 12(2): 205-221.
［14］Toma M, Ezekowitz JA, Bakal JA, et al. The relationship between left ventricular ejection fraction and mortality in patients with acute heart failure: insights from the ASCEND-HF Trial［J］. Eur J Heart Fail, 2014, 16(3): 334-341.
［15］Allessie MA, Boyden PA, Camm AJ, et al. Pathophysiology and prevention of atrial fibrillation［J］. Circulation, 2001, 103(5): 769-777.
［16］Liu Z, Finet JE, Wolfram JA, et al. Calcium/calmodulin-dependent protein kinase II causes atrial structural remodeling associated with atrial fibrillation and heart failure［J］. Heart Rhythm, 2019, 16(7): 1080-1088.
［17］Denham NC, Pearman CM, Caldwell JL, et al. Calcium in the pathophysiology of atrial fibrillation and heart failure［J］. Front Physiol, 2018, 9: 1380-1380.
［18］Staerk L, Sherer JA, Ko D, et al. Atrial fibrillation: Epidemiology, pathophysiology, and clinical outcomes［J］. Circ Res, 2017, 120(9): 1501.
［19］Takemoto Y, Ramirez RJ, Kaur K, et al. Eplerenone reduces atrial fibrillation burden without preventing atrial electrical remodeling［J］. J Am Coll Cardiol, 2017, 70(23): 2893-2905.
［20］Research C. Changes in connexin expression and the atrial fibrillation substrate in congestive heart failure［J］. Circ Res, 2009, 105(12): 1213-1222.
［21］Xie J, Yue L, Nattel S. Molecular determinants of cardiac fibroblast electrical function and therapeutic implications for atrial fibrillation［J］. Cardiovasc Res, 2011, 89(4): 744-753.
［22］Dong Q, Li S, Wang W, et al. FGF23 regulates atrial fibrosis in atrial fibrillation by mediating the STAT3 and SMAD3 pathways［J］. J Cell Physiol, 2019, 234(11): 19502-19510.
［23］Scott L, Li N, Dobrev D. Role of inflammatory signaling in atrial fibrillation［J］. Int J Cardiol, 2019, 287: 195-200.
［24］Duong E, Xiao J, Qi XY, et al. MicroRNA-135a regulates sodium-calcium exchanger gene expression and cardiac electrical activity［J］. Heart Rhythm, 2017, 14(5): 739-748.
［25］Wu Y,Liu Y,Pan Y,et al.MicroRNA-135a inhibits cardiac fibrosis induced by isoproterenol via TRPM7 channel［J］.Biomed Pharmacother,2018,104:252-260.
［26］冯凯, 杨蕾熙, 成祎琳, 等. 乙酰胆碱合并氯化钙静脉注射致兔和大鼠房颤模型的比较［J］. 实验动物与比较医学, 2019, 39(5): 371-376.

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