Effects of triptolide on lipopolysaccharide-induced acute lung injury in rats

Abstract

Objective To investigate the effects of triptolide on lipopolysaccharide (LPS)-induced acute lung injury in rats.Methods Sixty-five male SD rats weighing 200-250 g were randomly divided into 5 groups: control group (group C,n =5),LPS group (group L,n =15),different doses of triptolide groups (groups TP1-3,n =15).In group C normal saline was injected iv and 1％ DMSO injected intraperitoneally(ip).In group L LPS 5 mg/kg was injected iv and 1％ DMSO injected ip.In groups TP1-3 LPS 5 mg/kg was injected iv and triptolide 25,50 and 100 μg/kg was injected ip respectively.Blood samples were collected at 1 h before administration and 1,3,6 and 12 h after administration for blood gas analysis.The animals were sacrificed at 12 h after administration.TNF-α concentrations in serum and bronchoalveolar lavage fluid (BALF) were determined by ELISA.The lungs were removed for microscopic examination,evaluation of diffuse alveolar damage (DAD) score and determination of W/D lung weight ratio and the expression of Toll-like receptor4 (TLR4) protein and mRNA.Results Compared with group C,PaO2 was significantly decreased at 3,6 and 12 h after administration,DAD score and W/D lung weight ratio were increased in groups L and TP1-3,TNF-α concentrations in serum and BLAF were increased,expression of TLR4 mRNA and protein was up-regulated in groups L,TP1 and TP2,whlie TNF-α concentrations in serum and BLAF were significantly decreased,expression of TLR4 mRNA and protein was down-regulated in group TP3 ( P ＜ 0.05).Compared with groups L and TP1,PaO2 was significantly increased at 6 and 12 h after administration,DAD score,W/D lung weight ratio and TNF-α concentrations in serum and BLAF were decreased,expression of TLR4 mRNA and protein was down-regulated in groups TP2 and TP3 ( P ＜ 0.05).There was no siginificant difference in blood gas parameters,DAD score and W/D lung weight ratio between group L and group TP1 and between group TP2 and TP3 ( P ＞ 0.05).Compared with group TP2,TNF-α concentrations in serum and BLAF were significantly decreased,expression of TLR4 mRNA and protein was down-regulated in group TP3 (P ＜ 0.05).The lung pathologic injury was reduced in groups TP1-3 as compared with group L.Conclusion Triptolide can attenuate acute lung injury induced by LPS in a dose-dependent manner in rats,and the inhibition of up-regulation of TLR4 expression and release of TNF-α may be involved in the mechanism. Key words: Diterpenes ; Lipopolysaccharides ; Acute lung injury