达格列净通过调控TMEM16A改善2型糖尿病小鼠血管内皮衰老的机制研究

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Abstract Objective To explore the possible mechanism of DAP in the treatment of diabetic vascular complications from the perspective of vascular endothelial senescence. Methods The experimental mice were randomly divided into three groups: blank group, model group and DAP group. To construct diabetic mouse model by intraperitoneal injection of STZ, and each group was administered in a different way. Observe the general state of mice and detect their physiological parameters; The histopathology of the common carotid artery in each group was evaluated by HE staining and Masson staining. The contents of nitric oxide (NO), reactive oxygen species (ROS) and inflammatory factors in the serum of mice were detected by ELISA. Expression levels of the common carotid artery osteopontin, phosphorylation/signal transducer and activator of transcription 3, smooth muscle 22α, transmembrane protein 16A, p53 and p21 protein were detected by Western-blot. Results In DAP group, the mental state, activity, diet and excretion of mice were effectively improved, and the blood glucose value was significantly reduced. The expression of collagen fibers and the thickness of the arterial membrane were decreased significantly. In addition, the DAP group reversed the decrease of NO and inhibited the production of ROS, and the protein contents of p21, p53, OPN, TMEM16A and p-SATA3 in the common carotid artery tissues of mice were significantly reduced, the protein content of SM22α was significantly reversed. Conclusion DAP can effectively improve endothelial cell senescence in diabetic mice, alleviate common carotid artery vascular fibrosis in diabetic mice, and play a protective role in vascular senescence. The mechanism may be related to its inhibition of TMEM16A expression, ROS production and IL-6/IL-6R/STAT3 signaling pathway.

Key words： dapagliflozin endothelial cell senescence type 2 diabetes mellitus transmembrane protein16A signal transducer and activator of transcription 3 reactive oxygen species

Received: 15 June 2024

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	FENG Chunhui
	TIAN Yang
	SUN Wenyang
	HOU Yana
	LIU Jingfang

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FENG Chunhui,TIAN Yang,SUN Wenyang等. Study on the mechanism of dapagliflozin in improving vascular endothelial senescence by regulating TMEM16A mice with type 2 diabetes[J]. HuNan ShiFan DaXue XueBao(YiXueBan), 2024, 21(4): 7-11.

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http://yxb.hunnu.edu.cn/EN/ OR http://yxb.hunnu.edu.cn/EN/Y2024/V21/I4/7

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