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| Effects of Yixin Dingji Decoction on microRNA-1 and its regulatory protein connexin43 in rats with ischemic arrhythmia |
| DU Ye1 ZHANG Yiqing2 ZHANG Jing3 LIU Li2 MA Xuemiao4 YANG Ying2 |
1.Department of Endocrinology, the First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China; 2.Department of Cardiology, the First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
3.College of Traditional Chinese Medicine, Jiangsu Vocational College of Medicine, Jiangsu Province, Yancheng 224005, China;
4.Graduate School, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China
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Abstract Objective To explore the effects of Yixin Dingji Decoction on microRNA-1 (miRNA-1) and its regulatory protein connexin43 (Cx43) in rats with ischemic arrhythmia. Methods Sixty SPF 10-week-old male SD rats with a body weight of (250±20) g were divided into six groups by random number table method: sham operation group, model group, Propranolol control group, low, medium, and high dose groups of Yixin Dingji Decoction, with ten rats in each group. After feeding the animals for one week, gavage was administered. Low, medium, and high dose groups of Yixin Dingji Decoction were given 13.95, 27.90, 55.80 g/(kg·d) Yixin Dingji Decoction. Propranolol control group was given Propranolol (9.5 mg/7 ml) by gavage of 5 mg/kg a day. Model group and sham operation group were given the same amount of normal saline intragastric administration, one time a day. Each group was treated for two weeks. Except for sham operation group, the other groups were constructed immediately after the end of gavage, and the ischemic arrhythmia model of rats was established by ligation of the anterior descending branch of the left coronary artery. Sham operation group only thoracotomy without ligation. After modeling, the myocardial tissue of rats was collected, and the expression levels of miRNA-1 and Cx43 as well as the phosphorylation levels of Cx43 at Ser262 and Ser368 were detected by quantitative reverse transcription polymerase chain reaction and Western blot. Results Compared with sham operation group, the expression of miRNA-1 was increased and Cx43 was decreased in model group (P＜0.05). Compared with model group, miRNA-1 expression was decreased in low, medium, and high dose groups of Yixin Dingji Decoction, while Cx43 expression was increased in medium and high dose groups of Yixin Dingji Decoction (P＜0.05). Compared with low and medium dose groups of Yixin Dingji Decoction, miRNA-1 expression was decreased and Cx43 expression was increased in high dose group of Yixin Dingji Decoction (P＜0.05). Compared with the sham operation group, the phosp- horylation of Cx43 at sites Ser262 and Ser368 was decreased in the model group (P＜0.05). Compared with model group, the phosphorylation of Cx43 at sites Ser262 and Ser368 in high dose group of Yixin Dingji Decoction was increased (P＜0.05). Compared with low dose group of Yixin Dingji Decoction, the phosphorylation of Cx43 at sites Ser262 and Ser368 in high dose group of Yixin Dingji Decoction was increased (P＜0.05). The phosphorylation of Cx43 at sites Ser262 and Ser368 in high dose group of Yixin Dingji Decoction was not significantly different from that in medium dose group of Yixin Dingji Decoction (P＞0.05). Hematoxylin and eosin results showed that high dose group of Yixin Dingji Decoction could alleviate myocardial cell injury caused by ischemia reperfusion. Conclusion Yixin Dingji Decoction may effectively correct the expression of Cx43 by down-regulating the expression of miRNA-1 in myocardial tissue and weakening the post-transcriptional inhibition of Cx43. The pharmacology of Yixin Dingji Decoction is preliminarily explored in this study, which provided theoretical support for the effective prevention and treatment of ischemic arrhythmia.
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