Abstract: Objective To explore the effect of MCC950, selective inhibitor of NLRP3 inflammasome, on the development of pulmonary hypertension. Methods Male Sprague-Dawley rats were divided into 3 groups:control group, monocrotaline (MCT) group and MCT+MCC950 group. The right ventricular systolic pressure (RVSP), the index of right ventricular hypertrophy (RVHI) and lung morphological feature were assessed. The level of NLRP3, IL-1β and other molecular in lung were assessed by Western blotting and RT-PCR. Results The RVSP, RVHI and the remodeling of the small arteries in the MCT group were significantly higher than control group[(50.72±3.65)mmHg (1 mmHg=0.133 kPa) vs (24.29±1.28)mmHg, P=0.000] and (0.29±0.01 vs 0.61±0.04, P=0.000); while decreased after using MCC950 compared with MCT group[(34.19±1.94)mmHg vs (50.72±3.65)mmHg, P<0.01] and (0.48±0.03 vs 0.61±0.04, P<0.01). The protein expression level and the transcription of NLRP3, IL-1β and other molecular in lung of MCT group were increased. The administration of MCC950 decreased the protein expression level and the transcription of NLRP3, IL-1β and other molecular compared to MCT group. Conclusion MCC950 may attenuates pulmonary vascular remodeling and delaying the process of pulmonary hypertension by inhibit NLRP3 signaling pathway, which has the potential value of use in the treatment of pulmonary hypertension.

Key words: pulmonary hypertension, MCC950, NLRP3