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Modulation Effects And Mechanisms Of Liver X Receptors On Inflammatory Reaction Of Acute Lung Injury

Posted on:2013-02-27Degree:MasterType:Thesis
Country:ChinaCandidate:Y S WangFull Text:PDF
GTID:2234330374979364Subject:Clinical Anesthesiology
Abstract/Summary:
Objective: To observe the effect of liver X receptor agonists T0901317on the acutelung injury, and to explore the possible mechanisms of Liver X receptors on theinflammation of acute lung injury.Methods:60male SD rats were divided randomly into three groups: normal salinecontrol group, LPS processing group and T0901317+LPS processing group. With liver Xreceptor agonists T0901317irrigate after a week, we got acute lung injury model throughintravenous injection of LPS, while control group was injected with normal saline. Rateswere killed at2h,4h,6h,8h after intravenous injection of LPS or normal saline. Thepathomorphology change of lung tissue was evaluated by HE-stained lung sections,Arterial blood gas was analyzed, lung wet/dry weight radio and the protein of TNF-α,IL-1β, IL-6, IL-10and the neutrophilic granulocyte count in bronchoalveolar lavage fluidwere measured. The expression of LXRα mRNA and LXRβ mRNA were detected byreverse transcription-polymerase chain reaction (RT-PCR). Western-blot was used tomeasure the expression of NF-κBp65and ICAM-1.Results: Compared with the control group, LPS processing group and T0901317grouphave obvious acute lung injury performance: marked histological damage occurred,characterized by inflammatory cells infiltration, diffused alveolar septum edema andhemorrhaged in alveolar spaces and increased endothelial permeability; The PaO2wassignificantly reduced and The ratio of lung wet/dry weight has increased (P<0.05); Theprotein of TNF-α, IL-1β, IL-6, IL-10and the neutrophilic granulocyte count inbronchoalveolar lavage fluid were significantly increased (P<0.05); While compared with the LPS processing group, there was less damage in the T0901317+LPS processing group(P<0.05). The expression of LXRα mRNA and LXRβ mRNA in LPS processing groupwas significantly less than the control group and the difference have statisticalsignificance(P<0.05). The expression of NF-κBp65and ICAM-1in LPS processing groupand T0901317group were significantly more than the control group, while Comparedwith the LPS group there was less expression in the T0901317group, and thedifference have statistical significance(P<0.05).Conclusion:①The expression of LXRα and LXRβ in the LPS group wassignificantly reduced in acute lung injury model which induced by LPS.②Liver Xreceptor agonists T0901317could improve liver X receptors expression in the lung tissueand could relieve the inflammation of acute lung injury, which might be the liver Xreceptor in acute lung injury could reduce the expression of NF-κB and ICAM-1.
Keywords/Search Tags:LXR, acute lung injury, inflammation, T0901317
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