Abstract
Qiliqiangxin (QL) can attenuate myocardial remodeling and improve cardiac function in some cardiac diseases, including heart failure and hypertension. This study was to explore the effects and mechanism of QL on atrial structural remodeling in atrial fibrillation (AF). Twenty-one rabbits were randomly divided into a sham-operation group, pacing group (pacing with 600 beats per minute for 4 weeks), and treatment group (2.5 g/kg/day). Before pacing, the rabbits received QL-administered p.o. for 1 week. We measured atrial electrophysiological parameters in all groups to evaluate AF inducibility and the atrial effective refractory period (AERP). Echocardiography evaluated cardiac function and structure. TUNEL detection, hematoxylin and eosin (HE) staining, and Masson’s trichrome staining were performed. Immunohistochemistry and western blotting (WB) were used to detect alterations in calcium channel L-type dihydropyridine receptor α2 subunit (DHPR) and fibrosis-related regulatory factors. AF inducibility was markedly decreased after QL treatment. Furthermore, we found that AERP and DHPR were reduced significantly in pacing rabbits compared with sham rabbits; treatment with QL increased DHPR and AERP compared to the pacing group. The QL group showed significantly decreased mast cell density and improved atrial ejection fraction values compared with the pacing group. Moreover, QL decreased interventricular septum thickness (IVSd) and left ventricular end-diastolic diameter (LVEDD). Compared with the sham group, the levels of TGFβ1 and P-smad2/3 were significantly upregulated in the pacing group. QL reduced TGF-β1 and P-smad2/3 levels and downstream fibrosis-related factors. Our study demonstrated that QL treatment attenuates atrial structural remodeling potentially by inhibiting TGF-β1/P-smad2/3 signaling pathway.
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This work was supported by grants from the Harbin High Level Talent Fund (2013SYYRCYJ06) and the National Nature Scientific Foundation of China (No.81700305).
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Hou Tingting, Liu Guangzhong, Zang Yanxiang, and Li Weimin conceived and designed research. Hou TingTing, Liu Guangzhong, Zang Yangxiang, and Sun Li conducted experiments. Liu Guangzhong and Li Weimin contributed new reagents or analytical tools. Hou Tingting and Yu Dongdong analyzed data. Hou Tingting, Liu Guangzhong, and Zang Yanxiang wrote the manuscript. All authors read and approved the manuscript.
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Tingting, H., Guangzhong, L., Yanxiang, Z. et al. Qiliqiangxin attenuates atrial structural remodeling in prolonged pacing-induced atrial fibrillation in rabbits. Naunyn-Schmiedeberg's Arch Pharmacol 392, 585–592 (2019). https://doi.org/10.1007/s00210-018-01611-0
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DOI: https://doi.org/10.1007/s00210-018-01611-0