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Aim To explore the effect of dexmedetomidine (DEX) on acute lung injury (ALI) induced by lipopolysaccharide ( LPS) in rats and its mechanism. Methods The experiment included normal control group (Control) , DEX control group (DEX) , LPS-in-duced acute lung injury group (LPS) and LPS + DEX treatment group ( LPS + DEX ). Twenty-four hours after the successful modelling, the wet/dry weight ratio ( W/D) of the lung tissues of each group and the content of inflammatory cytokines IL-1 (3, TNF-a and IL-6 in the bronchoalveolar lavage fluid ( BALF) were measured; Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissues; im- munohistochemistry and Western blot were used to detect the expression of SIGIRR and NF-kB in lung tissues. Results Compared with control group, the levels of IL-1 (3, IL-6 and TNF-a in lung tissues of LPS group and BALF increased (P <0. 01). The lung tis sues showed obvious pathological damage of ALI, and the expression of SIGIRR was reduced ( P < 0. 01), the expression of phosphorylation activation of NF-kB increased (P <0. 01). Compared with LPS group, the W/D of lung tissues in LPS + DEX group and IL-1 [}, IL- in BALF 6 and TNF-a content were reduced (P < 0. 05 or P < 0. 01 ) . The pathological damage of lung tissues was significantly reduced, SIGIRR expression increased, and the activation of NF-kB phosphorylation decreased (P < 0. 01 ). Conclusions Dexmedetomidine can reduce SIGIRR degradation, inhibit the activation of NF-kB and reduce the inflammation, thereby reducing the acute lung injury induced by lipopolysaccharide in rats.
RESUMO
<p><b>OBJECTIVE</b>To observe the anti-inflammatory effect of total saponins of Panax japonicus on LPS-induced RAW264. 7 macrophages.</p><p><b>METHOD</b>The effect of total saponins of P. japonicus of different concentrations on RAW264. 7 cell viability was determined with the MTT method. The NO kit assay was adopted to detect the NO release of total saponins of P. japonicus to LPS-induced RAW264. 7 cells. The enzyme linked immunosorbent assay (ELISA) was used to detect the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1beta). The reverse transeriptase-polymerase chain reaction (RT-PCR) was used to determine the expression of inducible nitric oxide synthase (iNOS) ,TNF-alpha,IL-1beta. The protein expression of nuclear transcription factor-kappaB p65 (NF-kappaB p65) was tested by Western blot.</p><p><b>RESULT</b>The safe medication range of total saponins of P. japonicus was less than 80 mg x L(-1). Compared with the LPS model group, total saponins of P. japonicus high, middle and low dose groups (0.1, 1, 10, 40 mg x L(-1)) could significantly reduce the secretion of NO, TNF-alpha, IL-1beta of LPS-induced RAW264. 7 cells, and inhibit the expressions of iNOS, TNF-alpha and IL-1beta mRNA and the protein expression of NF-kappaB p65.</p><p><b>CONCLUSION</b>This study preliminarily proves the protective effect of total saponins of P. japonicus on LPS-induced RAW264.7 macrophages. Its action mechanism may be related to NF-kappaB signal pathway.</p>