The Improvement Effect of Sophoridine on Acute Respiratory Distress Syndrome in Rats by Regulating the Hippo-YAP Signaling Pathway
Objective:To investigate the improvement effect of sophoridine(SRI)on acute respiratory distress syndrome(ARDS)in rats and its mechanism of action.Methods:Totally 10 SD rats were randomly selected as blank group.A total of 50 SD rats were constructed an ARDS rat model by lipopolysaccharide(LPS)tracheal infusion method.The successfully modeled rats were randomly divided into model group,low-dose SRI group,medium-dose SRI group,high-dose SRI group and Vitiporfin+high-dose SRI group,with 10 rats in each group.After 2 hours of modeling,the low,medium and high-dose SRI groups were given intraperitoneal injections of low(2 mg/kg),medium(6 mg/kg)and high(12 mg/kg)doses of SRI,respectively.The Verteporfin+high-dose SRI group was given intraperitoneal injections of SRI(12 mg/kg)on the basis of intraperi-toneal injections of Verteporfin(100 mg/kg).The blank group and model group were intraperitoneally injected with an equal volume of physiological saline.The blood oxygen partial pressure(PaO2),PaO2/inhaled oxygen concentration(FiO2),and lung wet/dry(W/D)ratio were measured in 10 hours.Hematoxylin-eosin staining was applied to observe pathological changes in lung tissue and score pathological injury,and enzyme linked immunosorbent assay(ELISA)was applied to detect the levels of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β)and IL-10 in alveolar lavage fluid(BALF).BCA was applied to detect total protein levels in BALF.Giemsa staining was applied to detect the numbers of macrophages and neutrophils in BALF.MDA was detected by ELISA,and SOD was detected by colorimetry.MPO activity was detected by fluorescence.Western blotting was applied to detect the expression of Hippo-YAP pathway proteins.Results:Compared with the blank group,the lung tissue structure was destroyed in the model group and a large number of inflammatory cells infiltrated.Compared with the model group,the lung tissue structure recovered in low,medium and high-dose SRI groups.Compared with high-dose SRI group,Verteporfin+high-dose SRI group showed more lung tissue injury,with obvious swelling and degeneration of alveoli and inflammatory cell infiltration.The model group showed lower PaO2 and PaO2/FiO2 than blank group,while higher W/D ratio and pathological injury score than blank group(P＜0.05).The low,medium and high dose SRI groups showed higher PaO2 and PaO2/FiO2 than model group,while lower W/D ratio and pathological injury score than model group(P＜0.05).The Verteporfin+high-dose SRI group showed lower PaO2 and PaO2/FiO2 than high-dose SRI group,while higher W/D ratio and pathological injury score than high-dose SRI group(P＜0.05).The model group showed higher levels of TNF-α,IL-1β,IL-10,total protein,macrophage and neutrophil count in BALF than blank group(P＜0.05).The low,medium and high dose SRI groups showed lower levels of TNF-α,IL-1β,total protein,macrophage and neutrophil count in BALF than model group,while higher IL-10 level in BALF than model group(P＜0.05).Verteporfin+high-dose SRI group showed higher levels of TNF-α,IL-1 β,total protein,macrophage and neutrophil count in BALF than high-dose SRI group,while lower IL-10 levels in BALF than high-dose SRI group(P＜0.05).The model group showed higher relative expression levels of MDA,MPO,p-YAP protein and p-LATS1/LATS1 in lung tissue than blank group,while lower relative expression levels of SOD.YAP and TEAD1 protein than blank group(P＜0.05).The low,medium and high dose SRI groups showed lower relative expression levels of MDA,MPO,p-YAP protein and p-LATS1/LATS1 in lung tissue than model group,while higher relative expression levels of SOD,YAP and TEAD1 protein than model group(P＜0.05).The Verteporfin+high-dose SRI group showed higher relative expression levels of MDA,MPO,p-YAP protein and p-LATS1/LATS1 in the lung tissue than those high-dose SRI group,while lower relative expression levels of SOD,YAP and TEAD1 protein than high-dose SRI group(P＜0.05).Conclusion:SRI can inhibit inflammatory response and oxidative stress in ARDS rats,and its mechanism of action may be related to the activation of the Hippo-YAP signaling pathway.
万方数据
维普
