Jichu yixue yu linchuang (Dec 2021)

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

  • ZHANG Zhi-min, GUO Li-sha, MA Li-qun, REN Ke, LU Jun, WEI Xing, LI Hui-jie, ZHOU Sheng-hua

Journal volume & issue
Vol. 41, no. 12
pp. 1742 – 1748

Abstract

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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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