厄洛替尼对脂多糖诱导的巨噬细胞炎症反应和小鼠急性肺损伤的影响

doi:10.13481/j.1671-587x.20160308

Abstract

Abstract:

Objective: To investigate the effects of erlotinib on the inflammatory response of macrophages and acute lung injury(ALI ) induced by lipopolysaccharides(LPS)in the mice,and to reveal their mechanisms. Methods: The murine bone marrow derived macrophages were randomly divided into control group,erlotinib group,LPS group, and LPS+erlotinib group. The expression levels of tumor necrosis factor α(TNF-α) in the macrophages in various groups were detected by ELISA method and the phosphorylation levels of p38 and ERK1/2 were tested by Western blotting method. A total of 16 male mice were randomly divided into control group(saline),erlotinib group(45 mg·kg^-1 erlotinib for 3 d+saline),LPS group(saline+5 mg·kg^-1 LPS),LPS+erlotinib group(45 mg·kg^-1erlotinib+5 mg·kg^-1 LPS). The expression levels of TNF-α in the macrophages in serum was detected by ELISA method and the phosphorylation levels of p38 and ERK1/2 were tested by Western blotting method;the pathomorphology of lung tissue of the mice in various groups was observed by HE staining. Results: Compared with control group, the expression levels of TNF-α in the macrophages and serum of the mice,and the phosphorylation levels of ERK1/2 and p38 in the macrophages and lung tissue of the mice in erlotinib group had no significant difference(P>0.05),and the pathomorphology of lung tissue of the mice had no changes.Compared with erlotinib group,the expression levels of TNF-α in the macrophoages and serum of the mice and the phosphorylation levels of ERK1/2 and p38 in the macrophages and lung tissue of mice in LPS group were significantly increased(P<0.05),and the pathomorphology of LPS-induced ALI could be found.Compared with LPS group,the expression levels of TNF-α in the macrophages and serum of the mice and the phosphorylation levels of ERK1/2 and p38 in the macrophages and lung tissue of the mice in LPS+erlotinib group were decreased(P<0.05),and the pathomorphology of ALI was improved. Conclusion: Erlotinib can reduce the systemic inflammatory response of the ALI mice by inhibiting the phosphorylation levels of p38 and ERK1/2 of macrophages and the expression level of TNF-α to protect the ALI to a certain degree.

Key words: erlotinib, macrophages, tumor necrosis factor alpha, acute lung injury

CLC Number:

R563

WANG Xiaofei, QIN Zaisheng. Effects of erlotinib on inflammatory response of marcrophages and ALIinduced by lipopolysaccharides in mice[J].Journal of Jilin University Medicine Edition, 2016, 42(03): 457-461.

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Effects of erlotinib on inflammatory response of marcrophages and ALIinduced by lipopolysaccharides in mice

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