| Objective:To investigate the effect of atorvastatin calcium(AVT)on lipopolysaccharide(LPS)-induced acute lung injury(ALI)in mice via nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)pathway.Methods:Stochastically assigned fifteen female BALB/c mice to the NS group(injection of 0.9%NaCl),LPS group(induction of ALI model by intratail injection of LPS)and LPS+AVT group(ALI model by intragastric administration of AVT),each group 5 mice.All the mice were sacrificed since successfully induced in ALI model 6h later.The arterial blood of each group was taken for examination,the partial pressure of oxygen(PaO2)was obtained.Pathological changes appeared by HE staining were observed via optical microscope,wet/dry ratio(W/D)was also determined.ELISA and western blot were used respectively to measure the expression of inflammatory cytokines including interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α)in bronchoalveolar lavage fluid(BALF)and proteins of Nrf2 and HO-1 in lung tissues.Results:PaO2 in NS group,LPS group and LPS+AVT group were respectively[(89.66±8.54),(50.88±6.26),(67.84±5.76)mmHg];W/D were[(3.12±0.54),(4.95±0.60),(3.85±0.46)];IL-β[(37.95±6.18),(115.09±12.42),(75.61±7.89)pg/ml];TNF-α were[(63.66±20.71),(330.99±41.71),(220.87±28.89)pg/ml];Nrf2 were[(0.43± 0.03),(0.08±0.02),(0.22±0.03)]and HO-1 were[(0.59±0.07),(0.09±0.03),(0.22±0.03)].Compared with NS group,alveolar structure in LPS group was more distorted,alveolar septa was more thickened,alveolar spaces were accumulated with inflammatory cells;the levels of PaO2,Nrf2 and HO-1 protein in pulmonary tissue were decresed(P<0.05);while W/D,IL-1β and TNF-α in BALF were increased(P<0.05).Compared with LPS group,structure distortion,alveolar septa thickening and inflammatory cells accumulation were reduced;the levels of PaO2,Nrf2 and HO-1 protein in lung tissues were increased(P<0.05),while W/D,IL-1β and TNF-α in BALF were decreased(P<0.05).Conclusion:1、AVT reduced damage of lung tissue structure in LPS-induced ALI mice.2、AVT improved PaO2 in LPS-induced ALI mice,and also reduced the levels of TNF-α and IL-1β in BALF.3、AVT may protect LPS-induced ALI mice via activation of Nrf2/HO-1 pathway. |
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