Dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failure

Objective To observe the influence of dapagliflozin on ERS of myocardial tissues from rats with heart failure, and explore the its relationship with myocardial remodeling. Methods The rats were divided into the control group, model group (with aortic coarctation, TAC) and Dapagliflozin interv...

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Main Author: ZHANG Zhi-min, GUO Li-sha, MA Li-qun, REN Ke, LU Jun, WEI Xing, LI Hui-jie, ZHOU Sheng-hua
Format: Article
Language:zho
Published: Institute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College. 2021-12-01
Series:Jichu yixue yu linchuang
Subjects:
Online Access:http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/a200965.pdf
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author ZHANG Zhi-min, GUO Li-sha, MA Li-qun, REN Ke, LU Jun, WEI Xing, LI Hui-jie, ZHOU Sheng-hua
author_facet ZHANG Zhi-min, GUO Li-sha, MA Li-qun, REN Ke, LU Jun, WEI Xing, LI Hui-jie, ZHOU Sheng-hua
author_sort ZHANG Zhi-min, GUO Li-sha, MA Li-qun, REN Ke, LU Jun, WEI Xing, LI Hui-jie, ZHOU Sheng-hua
collection DOAJ
description Objective To observe the influence of dapagliflozin on ERS of myocardial tissues from rats with heart failure, and explore the its relationship with myocardial remodeling. Methods The rats were divided into the control group, model group (with aortic coarctation, TAC) and Dapagliflozin intervention group (with Dapagliflozin 0.5 and 1.0 mg/kg given by gavage once daily). Non-invasive rat tail artery manometer was used to detect mean arterial pressure. Weigh body weight, whole heart weight and left ventricular weight were recorded to calculate the rat myocardial hypertrophy index HWI and LVWI. Small animal ultrasound was used to detect rat heart function. The morphological changes of cardiomyocytes was microscopied with HE staining. Immuno-histochemistry and Western blot were used to detect GRP78 and CHOP expression in rat myocardial tissue. Results Compared with the control group, MAP, HWI and LVWI in the model group were significantly increased (P<0.01), EF and FS decreased significantly (P<0.01). Compared with the model group, HWI and LVWI were reduced (P<0.05), EF and FS were increased (P<0.05) in dapagliflozin group. HE staining showed that the myocardial fibers in control group were neatly arranged and morphologically regular; in model group, the myocardial fibers were excluded from the disorder, the morphology was irregular, and the tissue was evacuated; the myocardial fibers in dapagliflozin group were better than that of model group. Compared with control group, the expression of GRP78 and CHOP in the myocardium of model group was significantly increased(P<0.01);compared with model group, the expression of GRP78 and CHOP in dapagliflozin group was reduced (P<0.05). Conclusions Dapagliflozin obviously inhibits ERS, down-regulates the expression of GRP78 and CHOP, protects cardiomyocytes, more effectively relieves ventricular remodeling and improves cardiac function. ERS may be one of the molecular biological mechanisms of Dapagliflozin.
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spelling doaj.art-186fcd552bac4bfd88f509f545ed3ae72024-01-05T03:07:37ZzhoInstitute of Basic Medical Sciences and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences / Peking Union Medical College.Jichu yixue yu linchuang1001-63252021-12-01411217421748Dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failureZHANG Zhi-min, GUO Li-sha, MA Li-qun, REN Ke, LU Jun, WEI Xing, LI Hui-jie, ZHOU Sheng-hua01. Department of Cardiology; 2. Department of Health,General Hospital of Xinjiang Military Region, Urumqi 830000,ChinaObjective To observe the influence of dapagliflozin on ERS of myocardial tissues from rats with heart failure, and explore the its relationship with myocardial remodeling. Methods The rats were divided into the control group, model group (with aortic coarctation, TAC) and Dapagliflozin intervention group (with Dapagliflozin 0.5 and 1.0 mg/kg given by gavage once daily). Non-invasive rat tail artery manometer was used to detect mean arterial pressure. Weigh body weight, whole heart weight and left ventricular weight were recorded to calculate the rat myocardial hypertrophy index HWI and LVWI. Small animal ultrasound was used to detect rat heart function. The morphological changes of cardiomyocytes was microscopied with HE staining. Immuno-histochemistry and Western blot were used to detect GRP78 and CHOP expression in rat myocardial tissue. Results Compared with the control group, MAP, HWI and LVWI in the model group were significantly increased (P<0.01), EF and FS decreased significantly (P<0.01). Compared with the model group, HWI and LVWI were reduced (P<0.05), EF and FS were increased (P<0.05) in dapagliflozin group. HE staining showed that the myocardial fibers in control group were neatly arranged and morphologically regular; in model group, the myocardial fibers were excluded from the disorder, the morphology was irregular, and the tissue was evacuated; the myocardial fibers in dapagliflozin group were better than that of model group. Compared with control group, the expression of GRP78 and CHOP in the myocardium of model group was significantly increased(P<0.01);compared with model group, the expression of GRP78 and CHOP in dapagliflozin group was reduced (P<0.05). Conclusions Dapagliflozin obviously inhibits ERS, down-regulates the expression of GRP78 and CHOP, protects cardiomyocytes, more effectively relieves ventricular remodeling and improves cardiac function. ERS may be one of the molecular biological mechanisms of Dapagliflozin.http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/a200965.pdfdapagliflozin|heart failure|rat|endoplasmic reticulum stress|left ventricular remodeling
spellingShingle ZHANG Zhi-min, GUO Li-sha, MA Li-qun, REN Ke, LU Jun, WEI Xing, LI Hui-jie, ZHOU Sheng-hua
Dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failure
Jichu yixue yu linchuang
dapagliflozin|heart failure|rat|endoplasmic reticulum stress|left ventricular remodeling
title Dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failure
title_full Dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failure
title_fullStr Dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failure
title_full_unstemmed Dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failure
title_short Dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failure
title_sort dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failure
topic dapagliflozin|heart failure|rat|endoplasmic reticulum stress|left ventricular remodeling
url http://journal11.magtechjournal.com/Jwk_jcyxylc/fileup/1001-6325/PDF/a200965.pdf
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