Tolvaptan attenuates atrial remodeling in rats undergoing chronic intermittent hypoxia via miRNA-21
10.3760/cma.j.issn.0253?3758.2019.08.005
- VernacularTitle:托伐普坦通过调控微小RNA?21改善大鼠心房重构
- Author:
Zuowang MA
1
;
Kai ZHANG
;
Weiding WANG
;
Ruimeng LIU
;
Yuanyuan XU
;
Yue ZHANG
;
Meng YUAN
;
Guangping LI
Author Information
1. 天津医科大学第二医院心脏科天津心血管病离子与分子机能重点实验室天津心脏病学研究所300211
- Keywords:
Atrial fibrillation;
MicroRNAs;
Atrial remodeling;
Tolvaptan
- From:
Chinese Journal of Cardiology
2019;47(8):614-621
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects and potential mechanisms of tolvaptan on chronic intermittent hypoxia (CIH)?induced atrial remodeling in rats. Methods A total of 45 Sprague?Dawley rats were divided into 3 groups by the random number table: control group, CIH group (6 h/d for 30 days), CIH plus tolvaptan group (8 mg·kg-1·d-1 per gavage for 30 days). Echocardiography examination was performed after 30 days. Thereafter, 5 rats were randomly chosen for histology evaluation, 5 for molecular biological examinations and another 5 rats underwent isolated heart electrophysiology study in each group. Protein and mRNA expression levels of miRNA?21, Spry1, PTEN, ERK/p?ERK, MMP?9, PI3K, AKT/p?AKT were detected. Results Compared to the rats in control group, rats in the CIH group showed higher atrial interstitial collagen deposition (P<0.001), increased atrial fibrillation inducibility (P=0.022). The results of immunohistochemistry staining showed that the mean optical density (MOD) of ERK, p?ERK and MMP?9 were significantly increased (all P<0.05), the MOD of Spry1 and PTEN were significantly decreased (both P<0.05), above changes could be significantly reversed by cotreatment with tolvaptan. No significant differences were detected in PI3K and AKT among the three groups (P>0.05). In addition, compared with rats in control group, mRNA levels of miRNA?21, MMP?9, PI3K, AKT, and protein levels of ERK, p?ERK, MMP?9 were significantly increased in CIH group(all P<0.05), whereas protein levels of Spry1, PI3K, p?AKT were significantly decreased (all P<0.05). Above changes could be significantly attenuated. Conclusions CIH induces significant atrial remodeling in this rat model, which can be attenuated by tolvaptan possibly through modulating miRNA?21/Spry1/ERK/MMP?9 and miRNA?21/PTEN/PI3K/AKT signaling pathways.
