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Protective effect of ulinastatin plus methylprednisolone on endotoxin-induced acute lung injury in rats

Yongqi Hu

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Abstract

Objective:To explore the protective effect and the mechanism of combination of ulinastatin with methylprednisolone on endotoxin(LPS)-induced acute lung injury(ALI) in rats.Methods: ALI was induced by sublingual venous injection of LPS(5mg·kg-1) in rats.Rats(n=120) were randomly divided into 5 groups,and treated with saline(10mL·kg-1) in normal or ALI rats,and methylprednisolone(20mg·kg-1),ulinastatin(100000U·kg-1) or their combination(methylprednisolone 15mg·kg-1+ulinastatin 100000U·kg-1) in ALI rats.At 2,6,12 and 24h after the treatments,the serum IL-6 and TNF-a levels were detected by ELISA,the relative content of lung NF-κB/p65 were determined by ELISA,and the expression of TNF-a mRNA in lung tissue by RT-PCR.Results: As compared with normal control,the serum IL-6,TNF-a,and lung NF-κB/p65 and TNF-a mRNA were significantly increased after ALI(P0.05).Methylprednisolone,ulinastatin and the combination significantly attenuated theses changes(P0.05);the combination was more effective than methylprednisolone or ulinastatin alone(P0.05).Conclusion: The combination of ulinastatin with methylprednisolone attenuates LPS-induced ALI in reducing the increased serum IL-6 and TNF-a,and inhibiting lung expression of TNF-a mRNA and NF-κB/p65.

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Objective:To explore the protective effect and the mechanism of combination of ulinastatin with methylprednisolone on endotoxin(LPS)-induced acute lung injury(ALI) in rats.Methods: ALI was induced by sublingual venous injection of LPS(5mg·kg-1) in rats.Rats(n=120) were randomly divided into 5 groups,and treated with saline(10mL·kg-1) in normal or ALI rats,and methylprednisolone(20mg·kg-1),ulinastatin(100000U·kg-1) or their combination(methylprednisolone 15mg·kg-1+ulinastatin 100000U·kg-1) in ALI rats.At 2,6,12 and 24h after the treatments,the serum IL-6 and TNF-a levels were detected by ELISA,the relative content of lung NF-κB/p65 were determined by ELISA,and the expression of TNF-a mRNA in lung tissue by RT-PCR.Results: As compared with normal control,the serum IL-6,TNF-a,and lung NF-κB/p65 and TNF-a mRNA were significantly increased after ALI(P0.05).Methylprednisolone,ulinastatin and the combination significantly attenuated theses changes(P0.05);the combination was more effective than methylprednisolone or ulinastatin alone(P0.05).Conclusion: The combination of ulinastatin with methylprednisolone attenuates LPS-induced ALI in reducing the increased serum IL-6 and TNF-a,and inhibiting lung expression of TNF-a mRNA and NF-κB/p65.

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Available abstract

Objective:To explore the protective effect and the mechanism of combination of ulinastatin with methylprednisolone on endotoxin(LPS)-induced acute lung injury(ALI) in rats.Methods: ALI was induced by sublingual venous injection of LPS(5mg·kg-1) in rats.Rats(n=120) were randomly divided into 5 groups,and treated with saline(10mL·kg-1) in normal or ALI rats,and methylprednisolone(20mg·kg-1),ulinastatin(100000U·kg-1) or their combination(methylprednisolone 15mg·kg-1+ulinastatin 100000U·kg-1) in ALI rats.At 2,6,12 and 24h after the treatments,the serum IL-6 and TNF-a levels were detected by ELISA,the relative content of lung NF-κB/p65 were determined by ELISA,and the expression of TNF-a mRNA in lung tissue by RT-PCR.Results: As compared with normal control,the serum IL-6,TNF-a,and lung NF-κB/p65 and TNF-a mRNA were significantly increased after ALI(P0.05).Methylprednisolone,ulinastatin and the combination significantly attenuated theses changes(P0.05);the combination was more effective than methylprednisolone or ulinastatin alone(P0.05).Conclusion: The combination of ulinastatin with methylprednisolone attenuates LPS-induced ALI in reducing the increased serum IL-6 and TNF-a,and inhibiting lung expression of TNF-a mRNA and NF-κB/p65.

Key concepts: Ulinastatin, Methylprednisolone, Medicine, Lung, Tumor necrosis factor alpha, Saline, Pharmacology, Corticosteroid

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