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《Chinese Journal of Pathophysiology》 2007-04
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Protective role of endogenous hydrogen sulfide in cholecystokinin octapeptid against acute lung injury induced by lipopolysaccharide

TIAN Feng-jun,LING Yi-ling,HUANG Xin-li,WEI Peng,ZHOU Xiao-hong(Department of Pathophysiology,Hebei Medical University,Shijiazhuang 050017,China.)  
AIM: To explore the role of endogenous hydrogen sulfide(H2S) in the mechanism of cholecystokinin octapeptide(CCK-8) to alleviate acute lung injury(ALI) induced by lipopolysaccharide(LPS).METHODS: Eighty-four Sprague-Dawley rats were randomly divided into seven groups: control,LPS(instilled intratracheally to reproduce the model of ALI),NaHS(H2S donor) +LPS,propargylglycine [inhibitor of cysathionine-γ-lyase(CSE),PPG]+LPS,CCK-8+LPS,PPG+CCK-8+LPS and CCK-8 group.Animals were sacrificed at 4 h and 8 h after agent instillation.The wet and dry ratio(W/D) of the lung weight was measured and calculated.Morphological changes of lung tissues were observed.H2S concentration in plasma,malondialdehyde(MDA) content,myeloperoxidase(MPO) and CSE activities in the lung were determined.Furthermore,the level of P-selectin of lung tissue was measured by radioimmunoassay,the CSE mRNA expression in the lung was detected by RT-PCR,and the protein content in bronchoalveolar lavage fluid(BALF) was detected.RESULTS: Compared with control,severe injury of lung tissues and increase in W/D,protein content in BALF,MDA content,MPO activity and P-selectin level in the lung were observed in rats treated with LPS.LPS also lead to a drop in plasma H2S concentration,lung CSE activity and CSE mRNA expression.Administration of NaHS before LPS could attenuate the changes induced by LPS,while H2S concentration,CSE activity and CSE mRNA expression were higher than those in LPS group.However,pre-treatment with PPG exacerbated the lung injury induced by LPS,H2S concentration,CSE activity and CSE mRNA expression were lower than those in LPS and CCK-8 +LPS group,respectively.CONCLUSION: CCK-8 attenuates LPS-induced acute lung injury by means of anti-oxidation and inhibition of PMN adhesion and aggregation,both of which are mediated by endogenous H2S.
【Fund】: 河北省科技厅资助项目(No.06276102D-24)
【CateGory Index】: R563.8
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