利拉鲁肽对缺氧和高糖所致心肌细胞钙超载和细胞凋亡的影响

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Abstract Objective To investigate the effect and possible mechanism of liraglutide on hypoxia and high glucose-induced calcium overload and apoptosis in neonatal rat cardiomyocytes in vitro.Methods A model of hypoxia and high glucose was established using primarily cultured neonatal rat cardiomyocytes. Then, cells were divided into six groups: normal control group, liraglutide control group, hypoxia and high glucose model group, liraglutide treatment group, GLP-1R antagonist group, and high osmolality control group. The concentration of intracellular dissociative calcium in myocardial cells was determined with fluorospectrophotometry. The levels of Ca²⁺-ATPase, Na⁺-K⁺-ATPase and ROS were measured with biochemical approaches. The apoptosis rate was observed by a flow cytometer. The level of μ-calpain mRNA was examined with RT-PCR method. The level of caspase-3 was measured with ELISA.Results Compared with normal control group, the levels of expression of ROS, caspase-3, and μ-calpain mRNA were significantly increased in hypoxia and high glucose model group (P<0.01), the activity of Ca²⁺-ATPase and Na⁺-K⁺-ATPase decreased (P<0.01), the concentration of free Ca²⁺ increased from 117.19±15.04 nmol/L to 508.53±26.11 nmol/L, and the apoptosis rate increased from (3.95±0.12)% to (31.03±4.30)%. Liraglutide improved the parameters mentioned above (P<0.01). However, exendin(9-39), an antagonist of GLP-1R, attenuated the protective effect of liraglutide under hypoxia and high glucose.Conclusions Liraglutide can obviously inhibit calcium influx of myocardial cells and μ-calpain up-regulation, and decrease the level of caspase-3 and cell apoptosis.

Key words： liraglutide cardiomyocyte hypoxia high glucose calcium overload apoptosis

Received: 08 November 2016

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	Articles by authors
	LI Yinke
	SHI Qiongzhi
	CHEN Chen
	LIAO Xiangru
	and XIE Xiangyang

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LI Yinke,SHI Qiongzhi,CHEN Chen等. Effects and possible mechanism of liraglutide on hypoxia and high glucose-induced calcium overload and apoptosis in neonatal rat cardiomyocytes in vitro[J]. Med. J. Chin. Peop. Armed Poli. Forc., 2017, 28(7): 678-682.

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http://journal08.magtechjournal.com/Jwk_wjyx/EN/ OR http://journal08.magtechjournal.com/Jwk_wjyx/EN/Y2017/V28/I7/678

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