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The Effect Of Atorvastatin Calcium On Rats With Acute Lung Injury Induced By Lipopolysaccharides

Posted on:2011-04-13Degree:MasterType:Thesis
Country:ChinaCandidate:M Y JiaFull Text:PDF
GTID:2154360308972754Subject:Internal Medicine
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Objective:To observe the effect of Atorvastatin Calcium on the expression of nuclear factor-KB (NF-κB) in lung tissue and inflammatory factors such as tumor necrosis factor a (TNF-a), interleukin 1β(IL-1β) in BALF in SD rats with acute lung injury ruduced by lipopolysaccharide (LPS) by intravenous injection,and to Investigate the role of Atorvastatin Calcium in the SD rats with acute lung injury ruduced by lipopolysaccharide(LPS) Methods:Acute lung injury SD rats model was established by intravenous injection of lipopolysaccharide (LPS),90 Clean-type male SD rats were randomly divided into control group (18, referred to as N group, normal saline injected by intravenous), model group (18, referred to as L group, Endotoxin injected by intravenous 6mg/kg), the intervention group (54, referred to as T) [divided into 3 subgroups:T1 group (18):atorvastatin 5mg/kg/d and LPS 6mg/kg injected by intravenous group, T2 group (18):atorvastatin 10mg/kg/d and endotoxin 6mg/kg injected by intravenous group, T3 group (18):atorvastatin 20mg/kg/d and endotoxin 6mg/kg injected by intravenous group)],6 rats in each group were sacrificed in 2 hours,4 hours and 8 hours at 3 time points.The pathology of the right lung lower lobe lung was observed by HE staining. NF-κB expression in cytoplasm and the nucleus in upper and middle of the right lung was measured by Western blot (Western blot) and the concentrations of TNF-a, IL-1βin BALF were detected by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA)。Results:1:The pathology of the right lower lung in SD rats was observed under HE staining 200 times microscope.The group N was normal, but group L,group T were a large number of neutrophil infiltration companying with hemorrhage,formation of hyaline membrane. These results suggested that lung injury model succeeded. Lung injury evaluation were classified to five categories by the interstitial edema, hemorrhage, inflammatory cell accumulation or aggregation in the alveolar and pulmonary. The pathological scores in group L,T were significantly different from group N (P<0.05); while the pathology score in the group L was more serious than that in the group T, which was statistical significance (P<0.05).2:The expression of NF-κB in the cytoplasm in the lung tissue of group L and group T were significantly higher than those in the group N (P<0.05), but there was no significant difference between group L and group T (P> 0.05); While the expression of NF-κB in the nucleus in group L and group T was significantly higher than that in group N (P<0.05), L group increased significantly, which was significantly different between group L and group T (P<0.05), there was statistical significance. Secretion peak of NF-κB was all at 2 hours in the cytoplasm and nucleus in the group L and group T, and then it had a decreasing trend. The expression of NF-κB in the cytoplasm and nuclei among subgroups T showed no statistical significance (P> 0.05).3:The expression level of tumor necrosis factor a (TNF-a), interleukin 1β(IL-1β) in bronchoalveolar lavage fluid (BALF) in group L and group T significantly increased, There was significantly difference between group T and group L from group N (P<0.05). Observing the secretion trends,tumor necrosis factor a (TNF-a) peaked at 2 hours,and interleukin 1β(IL-1β)peaked at 4-hours; These indicators among subgroups T showed no statistical significance (P>0.05)4:The expression of NF-κB in nucleus,and the espression of tumor necrosis factor a (TNF-a),and interleukin 1β(IL-1β) in bronchoalveolar lavage fluid in the group L and group T were analysed by linear correlation analysis with SPSS software.The results indicated that they were positively correlated (r= 0.722, P<0.05; r= 0.333, P <0.05)。In group L and group T,the difference of the correlation coefficient might be related on the timing of cytokines secretion,and the secretion peak of nuclear factor-KB was before the 2 hours. Tumor necrosis factor a (TNF-a) peaked at 2 hour and interleukin 1β(IL-1β) peaked at 4 hour.However, there was no peak in group N.Conclusions:Atorvastatin calcium could reduce translocation of nuclear factor-KB from the cytoplasm to the nucleus in acute lung injury induced by LPS,and decrease the biological activity of nuclear factor-KB. Thus it maight indirectly affect the expression of inflammatory mediators such as tumor necrosis factor a,interleukin-1βand so on, reduce the acute lung injury induced by LPS.
Keywords/Search Tags:acute lung injury, atorvastatin, nuclear factor kappa B (NF-κB), tumor necrosis factor a (TNF-a), interleukin 1β(IL-1β)
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