| Pulmonary hypertension(PH)is a malignant cardiopulmonary syndrome in the clincal,Which its hemodynamics is defined as the mean pulmonary artery pressure at rest≥25 mmHg.The pathological features of PH are excessive pulmonary vasoconstriction and abnormal thickening of the vascular wall.Its etiology is also complicated and PH is hard to cure.Recently,the importantce of inflammation on the pathological process of PH has been confirmed one after another.Pyroptosis is a new way that releases a large number of inflammatory factors when cells died.Therefore,we start to search the pathogenesis of PH and explore the potential therapeutic targets from the perspective of pyroptosis.Puerarin is an isoflavone compound extracted from the traditional Chinese medicine Pueraria lobata root.It has the effects of protecting cardiovascular,lowering blood pressure and suppress proliferation.It can also play an anti-inflammatory effect by regulating various inflammatory cells,factors and related signal pathways.Although studies have shown that puerarin can delay the process of PH by reducing the level of inflammatory factors,but how puerarin mediates the occurrence and development of PH through pyroptosis has not been reported.This article takes SD rats and pulmonary artery smooth muscle cells(PASMCs)of rats as the research objects to explore whether puerarin exerts a protective effect on hypoxic PH by affecting the activity of NLRP3 inflammasomes,and provides a new theoretical basis for the prevention and treatment of PH.In this study,a hypoxic box was used to establish a PH rat model.Puerarin was given to hypoxic rats at a dose of 80 mg/kg,and the other groups were given the same dose of 0.5%sodium carboxymethyl cellulose.The model and prevention time were as follows On the 21st day,the aortic diameter measurement,pulmonary artery velocity time integral,right ventricular systolic pressure,right heart hypertrophy index,and H&E staining method were used to evaluate the PH rat model and the effect of puerarin.Hypoxic cells were cultured under the conditions of 5%CO2,3%O2,and 37℃ in vitro.Puerarin was administered to hypoxic cells at a dose of 0.2 mmol/L,and the other groups were given the same dose of dimethyl sulfoxide a day.Immunochemical method was used to detect the expression of Caspase-1 in lung tissues;Western blot was used to detect the expression of NLPR3,Caspase-1,IL-1β,ASC in lung tissues and PASMCs;MTT method was used to detect the effect of different concentrations of puerarin on the activity of PASMCs;Lactate dehydrogenase release test was used to detect the release of lactate dehydrogenase in PASMCs;Hoechst 33342/PI double staining test to detect the integrity of cell membranes.The results show that puerarin can improve the right heart function of PH rats and inhibit pathological pulmonary vascular remodeling.In vivo and in vitro experiments have shown that puerarin can inhibit pyroptosis.In order to further explore the mechanism of puerarin in PH rats,the NLRP3 overexpression plasmid was transfected into PASMCs in this experiment,and Western blot,lactate dehydrogenase release experiment and Hoechst 33342/PI double staining experiment were also used to detect scorch.Death level.The results show that the expression of key pyroptosis proteins increased,the release of lactate dehydrogenase and the proportion of pyroptosis-positive cells increased,and puerarin can reverse the above phenomenon by inhibiting the activity of NLRP3 inflammasome.The above results revealed that both in vitro and in vivo experiments confirmed that hypoxia can induce PASMCs pyroptosis and activate NLRP3 inflammasomes;puerarin can inhibit the pyroptosis of PASMCs by interfering with the activity of NLRP3 inflammasomes.In short,this study revealed the relationship between puerarin and PH from the perspective of cell pyroptosis,and verified the inhibitory effect through the NLRP3 signaling pathway,providing a reference for finding the pathogenesis of PH and clinical treatment drugs. |
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