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Protective Mechanism of Chloroquine on Lipopolysaccharide-Induced Acute Lung Injury in Rat

XIONG Yi1,HE Zhi-jiang2,WANG Xing-yong1,ZHOU Hai-yin1,HE Rong1,DING Miao1,QIU Chun-lan1,ZHOU Jing1,HE Yin1(1.Intensive Care Unit,Children′s Hospital of Chongqing Medical University,Chongqing 400014,China;2.Department of Pediatrics,Bao′an Maternity and Child Health Hospital,Shenzhen 518133,Guangdong Province,China)  
Objective To explore the protective effects and mechanisms of chloroquine on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in rat.Methods Ninety-six 40-50 days age SD male rats were randomly assigned to 3 groups: control group,model group and chloroquine treatment group.All rats in each group were divided into injected 2,4,8,12 hours subgroups.ALI model was induced by intravenous injection of LPS(6 mg/kg),chloroquine treatment group was immediately administered chloroquine(30 mg/kg) by intrape-ritoneal injection after they had been injected LPS,control group was intravenous injected of physiological saline,the injected fluid volume of 3 groups was equal.These animal were killed at the each observation time point.The lung wet/dry weight ratio(W/D),lung pathologic tissue score were detected with hematoxylin and eosin(HE) stain,alveolar macrophages(AM) apoptosis ratio was determined with terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL) method,nuclear factor-κBp65(NF-κBp65) expression was measured with immunohistochemistry technique,plasma level of IL-6 was determined with enzyme linked immunosorbent assay(ELISA),AM phagotrophic function with neutral red,and secretory phospholipase A2 typeⅡA(sPLA2ⅡA),Bcl-2,Bax genes expression were mea-sured with reverse transcription polymerase chain reation(RT-PCR) technique.Statistics analysis was carried out by SPSS 12.0 statistics software.Results Compared with control group,the lung W/D,lung pathologic tissue score,AM apoptosis ratio,AM NF-κBp65 expression,sPLA2ⅡA and Bax genes expression were significantly increased and AM phagotrophic function,Bcl-2 genes expression were significantly decreased in model group rats(Pa0.01).Compared with control group,plasma level of IL-6 obviously heightened after injected LPS(P0.01).These changes were inverted in chloroquine treatment group rats,the degree of lung injury was markedly relieved(Pa0.01).Conclusions In early ALI,chloroquine potentially down regulation expression of sPLA2ⅡA and Bax gene,up-regulation Bcl-2 genes expression of AM,inhibit activation of NF-κB in AM,enhance AM phagotrophic function,decrease AM apoptosis,which has protective function in LPS-induced ALI rats.
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