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 inje

ction 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 (sPLA

2

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 sPLA

2

ⅡA expression were increased

and AM Bcl-2 expression was decreased in model group (P0.05). These changes were inverted in rats of PDTC prevention group

and the degree of lung injury was markedly attenuated (P0.05).   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 sPLA

2

ⅡA while increasing Bcl-2 expression in AM

and thus suppressing AM apoptosis.