达格列净抑制血管紧张素Ⅱ诱导的心肌细胞肥大和凋亡

doi:10.3969/j.issn.1006-5725.2024.11.010

Abstract

Abstract:

Objective This study aimed to investigate the effect of Dapagliflozin on the hypertrophy and apoptosis of cardiomyocytes induced by angiotensinⅡ（Ang Ⅱ）. Methods Primary rat neonatal cardiomyocytes were isolated， cultured and randomly divided into 4 groups： control group， Ang Ⅱ group， dapagliflozin group 1 （0.5 μmol/L）， and dapagliflozin group 2 （2 μmol/L）. α-actin staining was used to detect cell area. qPCR was applied to detect embryonic gene transcription. Tunel staining was adopted to detect cell apoptosis level. The caspase3 kit was used to detect caspase3 activityand western blotting was used to detect classical signal molecules. Results The cell surface area of the Ang Ⅱ group was significantly larger than that of the control group （P < 0.05）. The cell surface area of the dapagliflozin group 1 and the dapagliflozin group 2 was significantly lower than that of the Ang Ⅱ group （P < 0.05）. The results of qPCR showed that the fetal gene transcription of Ang Ⅱ group was significantly higher than that of the control group （P < 0.05）； the fetal gene transcription of dapagliflozin group 1 and dapagliflozin group 2 was lower than that of Ang Ⅱ group （P < 0.05）. Tunel staining showed that the number of apoptosis in the Ang Ⅱ group was higher than that in the control group （P < 0.05）； the number of apoptosis in the dapagliflozin group 1 and the Dapagliflozin group 2 was lower than that in the Ang Ⅱ group （P < 0.05）. The caspase3 activity of the cells in the Ang Ⅱ group was higher than that of the control group （P < 0.05）but lower in dapagliflozin group 1 and the dapagliflozin group 2 （P < 0.05）. The results of Western blotting showed that the activation of insulin-like growth factor 1 receptor （IGF1R） and Akt in the Ang Ⅱ group was lower than that in the control group （P < 0.05）but increased in the dapagliflozin group 1 and 2 cells （P < 0.05）. Conclusion Dapagliflozin could directly act on cardiomyocytes to protect them from Ang Ⅱ-induced damage.

Key words: dapagliflozin, SGLT2 inhibitor, angiotensin Ⅱ, cardiomyocytes, insulin-like growth factor 1 receptor

CLC Number:

R542.2

Shuangyin SHAO,Xintong CAI,Lili XIAO,Lu. GAO. Dapagliflozin inhibits angiotensin Ⅱ⁃induced cardiomyocyte hypertrophy and apoptosis[J]. The Journal of Practical Medicine, 2024, 40(11): 1526-1530.

Figures/Tables 6

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References 20

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组别	ANP	BNP	β-MHC
对照组	1.0 ± 0.16	1.0 ± 0.14	1.0 ± 0.09
Ang Ⅱ组	3.9 ± 0.61^a	3.5 ± 0.41^a	3.29 ± 0.53^a
达格列净1组	2.3 ± 0.32^b	2.0 ± 0.13^b	2.4 ± 0.44^b
达格列净2组	1.6 ± 0.24^b	1.3 ± 0.17^b	1.5 ± 0.23^b
F值	80.28	87.56	96.34
P值	< 0.001	< 0.001	< 0.001

组别	IGF1R/GAPDH	P-AKT/T-AKT
对照组	0.64 ± 0.06	1.7 ± 0.11
AngⅡ组	0.25 ± 0.03^a	0.31 ± 0.03^a
达格列净1组	0.37 ± 0.02^b	0.87 ± 0.10^b
达格列净2组	0.47 ± 0.02^b	1.1 ± 0.06^b
F值	115.6	297.3
P值	< 0.001	< 0.001

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Dapagliflozin inhibits angiotensin Ⅱ⁃induced cardiomyocyte hypertrophy and apoptosis

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