Astragalus Polysaccharides Improve Pulmonary Hypertension In Rats By Reducing Calpain-1 Induced Inflammation

ObjectiveTo study the ameliorative effect of Astragalus polysaccharides(APS)on monocrotaline(MCT)-induced pulmonary hypertension in rats,and to further study the relevant mechanisms,so as to provide a new treatment plan for pulmonary hypertension.MethodsAnimal grouping: 10 healthy male Sprague-Dawley rats were randomly selected as a blank control group(CON).The remaining 50 rats were given intraperitoneal injection of monocrotaline(MCT)60mg/kg to induce pulmonary hypertension,and the rats were randomly divided into 5 groups: pulmonary hypertension model group,calpain-1 inhibition group(MDL28170 10mg/kg),nucleotide-binding oligomeric domain-like receptor protein 3(NLRP3)Inflammatory body inhibitor group(MCC950 3mg/kg),Astragalus polysaccharides low-dose group(APS 400mg/kg),Astragalus polysaccharides high-dose group(APS 800mg/kg).The calpian-1 inhibitor group and the NLRP3 inhibitor group intraperitoneally injected with the corresponding dose of the inhibitor weekly for 4 weeks,while the rest were intraperitoneally injected with the corresponding normal saline.The Astragalus polysaccharides treatment group was given corresponding dose according to body weight by gavage for 4weeks,the other groups were given corresponding dose of distilled water.Right ventricular pressure(RVSP)and right ventricular hypertrophy index were measured in rats [RV/(LV+S)].Calpain activity was detected with the kit,ELISA kit was used to detect the levels of interleukin-18(IL-18)and interleukin-1β(IL-1β)in lung tissues,The histological morphological differences of pulmonary artery were observed by HE staining,and the percentage of pulmonary arteriole wall thickness to outer diameter(WT%)and the percentage of pulmonary arteriole wall area to total area(WA%)were calculated.The expression level of calpain-1 in lung tissues was detected by immunohistochemistry.Western Blot method was used to detect the expression levels of calpain-1,NLRP3,ASC,caspase-1,cleaved caspase-3,Bcl-2,and Bax in lung tissue.ResultsCompared with the control group,the RVSP of rats in the PAH model group was significantly increased,and the right heart hypertrophy index was significantly increased.HE stained lung tissue sections showed that the rat pulmonary arterioles vascular smooth muscles were significantly hypertrophy,lumen stenosis and lung tissue.There are a large number of inflammatory cells were infiltrated around lung tissue.The expression of calpain-1,NLRP3,ASC,caspase-1,cleavedcaspase-3,Bcl-2 and Bax tissues increased,the activity of calpain increased,and the content of IL-1β and IL-18 in serum increased.Compared with the PAH model group,the RVSP of the rats in the Astragalus polysaccharide treatment group and the inhibitor group was significantly reduced,and the cardiac hypertrophy index was significantly reduced.From the HE-stained lung tissue sections,it was obvious that the rat pulmonary arterioles endothelial and smooth muscle Compared with the PAH model group,the proliferation of cells was improved,and the degree of inflammatory cell infiltration in the alveolar cavity was significantly reduced.Correspondingly,the expression of calpain-1,NLRP3,ASC,cleaved caspase-3,Bax and caspase-1 protein in the lung tissue decreased,the activity of calpain decreased,and the content of IL-1β and IL-18 in the serum decreased.ConclusionsAstragalus polysaccharides have protective effect on the pulmonary arteries of rats with MCT-induced pulmonary hypertension.The mechanism may be related to reducing the expression of calpain-1 and NLRP3 inflammasome by Astragalus polysaccharides.