Effect and mechanism of dapagliflozin on pulmonary arterial hypertension induced by monocrotaline in rats

SUN Qian; WANG Jian; LIU Fen; YAN Sulan; PENG Jianqiang; ZOU Qiongchao

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Journal of Hunan Normal University(Medical Science) ›› 2023, Vol. 20 ›› Issue (6) : 14-19.

Basic Medicine

Effect and mechanism of dapagliflozin on pulmonary arterial hypertension induced by monocrotaline in rats

SUN Qian, WANG Jian, LIU Fen, YAN Sulan, PENG Jianqiang, ZOU Qiongchao

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Abstract

Objective To investigate the effect of dapagliflozin (DAPA) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and its mechanism of action. Methods Thirty male SD rats were randomly divided into three groups: (1) Control group, (2) Model group: pulmonary arterial hypertension group, (3) DAPA group: dapagliflozin treatment group. Single subcutaneous injection of MCT (60 mg/kg) was administered to establish the PAH model. The control group and the MCT group were given 0.5% sodium carboxymethyl cellulose by gavage every day, while the DAPA group was given dapagliflozin (1 mg/kg) dissolved in 0.5% sodium carboxymethyl cellulose by gavage. After 21 days, the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of rats were measured, the percentage of pulmonary arteriolar wall thickness was measured by HE staining, pulmonary arterial α-smooth muscle actin was detected by immunohistochemistry, NLRP3, IL-1β, and IL-18 protein expression in lung tissue were detected by Western blot, and plasma IL-1β and IL-18 levels were measured by Elisa. Results DAPA significantly reduced RVSP and improved right ventricular hypertrophy in MCT-induced PAH rats, inhibited the thickening of pulmonary arterioles and decreased the degree of muscularization in PAH rats. Furthermore, DAPA inhibited the activation of the NLRP3 inflammasome in lung tissue and down-regulated the levels of IL-1β and IL-18 in lung tissue and plasma. Conclusion DAPA can reduce the RVSP, improve right ventricular hypertrophy and pulmonary vascular remodeling in MCT-induced PAH rats, which may be associated with its inhibition of NLRP3 inflammasome activation and downregulation of IL-18 and IL-1β expression levels.

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dapagliflozin / pulmonary artertension hypertension / pulmonary vascular remodeling / right ventricular hypertrophy

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SUN Qian, WANG Jian, LIU Fen, YAN Sulan, PENG Jianqiang, ZOU Qiongchao. Effect and mechanism of dapagliflozin on pulmonary arterial hypertension induced by monocrotaline in rats[J]. Journal of Hunan Normal University(Medical Science). 2023, 20(6): 14-19

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