Protective effects and mechanism of pyrrolidine dithiocarbamates on acute lung injury of LPS-induced septic rats

Objective To investigate the pathological process of lipopolysaccharide ( LPS) -induced acute lung injury ( ALI) in rats,and to explore the protective effects and mechanisms of pyrrolidine dithiocarbamates ( PDTC) on it. Methods Ninety-six SD male rats were randomly assigned into 3 groups: control group,model group,PDTC prevention group. ALI was induced by intravenous injection of LPS ( 6 mg/kg) ,and then these animal were respectively killed in 2,4,8 and 12 h after LPS injection. The rats from PDTC prevention group were given PDTC ( 120 mg/kg) by intraperitoneal injection in 30 min before the LPS injection. The lung wet/dry weight ratio was calcuated,lung pathology was observed with hematoxylin and eosin ( HE) staining, alveolar macrophages ( AM) apoptosis ratio with TUNEL method,nuclear factor-κBp65 ( NF-κBp65) expression with immunohistochemical staining,and mRNA expressions of secretory phospholipase A2 typeⅡA ( sPLA2 ⅡA) ,Bcl-2 and Bax with RT-PCR. Results Compared with control group,the lung wet/dry weight ratio, lung pathologic tissue score,AM apoptosis ratio,AM NF-κBp65 expression,and sPLA2 ⅡA expression were increased,and AM Bcl-2 expression was decreased in model group ( P 0. 05) . These changes were inverted in rats of PDTC prevention group,and the degree of lung injury was markedly attenuated ( P 0. 05) . Conclusion The prophylactic PDTC administration potentially exerts protective function in LPS-induced ALI rats, probably through inhibiting the activation of NF-κB,decreasing the expression of sPLA2 ⅡA while increasing Bcl-2 expression in AM,and thus suppressing AM apoptosis.