藏红花素缓解野百合碱诱导动脉型肺动脉高压大鼠右心室损伤的机制研究OA北大核心CSTPCD

AIM:To investigate whether crocin alleviates right ventricular injury induced by monocrotaline(MCT)in rats with pulmonary arterial hypertension(PAH),and to explore the underlying mechanisms.METHODS:Forty male SD rats were randomly divided into 4 groups:normal group,PAH group,crocin group and sildenafil group,with 10 rats in each group.The rats in PAH,crocin and sildenafil groups received subcutaneous injection of MCT(50 mg/kg)to establish the PAH model.Starting from the day of MCT injection,the rats in crocin group received crocin(200 mg/kg),the rats in sildenafil group received sildenafil(30 mg/kg),and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily.After 4 weeks,measurements of right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI)and right ventricular mass index(RVMI)were taken for the rats in each group.Tissue staining was conducted to observe pathological changes in the right ventricle,and the expression levels of inflammatory factors(IL-1β,IL-6 and TNF-α),the p38 MAPK/NF-κB inflammato-ry pathway,CCL2,CCR2,and the macrophage marker CD68 were assessed.RESULTS:Compared with PAH group,the rats in crocin and sildenafil groups exhibited significant reductions in RVSP,mPAP,RVHI and RVMI(P＜0.05).Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers.The down-regulation of the p38 MAPK/NF-κB pathway and inflammatory factors(IL-1β,IL-6 and TNF-α)was significant(P＜0.05).Additionally,the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased(P＜0.05).CONCLUSION:Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats,with its effica-cy comparable to that of sildenafil at the dosage utilized in this experiment.Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation.