The role of autophagy in cardiac hypertrophy induced by chronic intermittent hypoxia and the therapeutic effect of resveratrol
10.3760/cma.j.issn.0254-9026.2017.12.019
- VernacularTitle:自噬机制对慢性间歇低氧诱导大鼠心肌肥厚的影响以及白藜芦醇的干预作用
- Author:
Pingli LIN
1
;
Qichang LIN
Author Information
1. 福建医科大学附属第一医院呼吸与危重症医学科
- Keywords:
Sleep apnea,obstructive;
Cardiomyopathy,hypertrophic;
Autophagy
- From:
Chinese Journal of Geriatrics
2017;36(12):1356-1361
- CountryChina
- Language:Chinese
-
Abstract:
Objective To examine whether autophagy plays a role in the development of chronic intermittent hypoxia-induced cardiac hypertrophy,whether resveratrol can reverse the process by modulating autophagy and what molecular pathways are involved.Methods Rats were randomly divided into four groups.Eight rats were treated with normoxia (control group),eight were exposed to chronic intermittent hypoxia (CIH) (CIH group),eight were exposed to CIH plus resveratrol (RSV) (CIH+RSV group) and eight were exposed to CIH,RSV and chloroquine (Cq) (CIH + RSV+ Cq group).After treatment for seven weeks,the levels of LC3,Beclin,P62,ANP,β-MHC,AMPK,P-AMPK,mTOR,P-mTOR and cleaved-caspase 3 were detected by Western blot.The area of cardiomyocytes and the ratio of brotic area to the total area were obtained by HE and Sirius Red staining.Results Rats in the CIH+RSV group were associated with an increased ratio of LC3 Ⅱ /LC3 Ⅰ,increased Beclin levels and decreased P62 levels,compared with those in the control and CIH groups (all P＜0.05).After chloroquine injection,the ratio of LC3 Ⅱ/LC3 Ⅰ was markedly increased in the CIH+RSV+Cq group,compared with that in the CIH+RSV group (all P＜0.05).Moreover,the CIH group was associated with significantly increased area of cardiomyocytes,ratio of fibrotic area to the total area,and levels of ANP,β-MHC and cleaved-caspase 3,compared with the control group (all P＜0.05).However,their values markedly decreased in the CIH +RSV group and significantly increased in the CIH+RSV+Cq group,compared with the CIH group (all P＜0.05).Furthermore,there were tendencies of progressively increased levels of P-AMPK and decreased levels of P-mTOR among the control group,CIH group and CIH+RSV group (both P ＜ 0.05).However,levels of AMPK and mTOR were similar among the three groups (P ＞ 0.05).Conclusions Chronic intermittent hypoxia and resveratrol can affect the level of cardiac hypertrophy by autophagy through activating the AMPK/mTOR pathway.
