The role of erlotinib in the acute lung injury and the expression of surfactant protein A

Abstract

Objective To investigate the role of erlotinib in the expression of surfactant protein A (SP-A) in LPS-induced acute lung injury (ALI) of mice model. Methods C57BL/6 mice were randomly (random number)divided into control group (n=6), ER group (n=6), LPS group (n=6), and ER+LPS group (n=6). In the LPS group, 2 mg/kg LPS was instilled into trachea of mice to induce lung injury. In control group, normal saline was instilled into trachea of mice instead. In the ER+LPS group and ER group, 100 mg/kg of erlotinib was instilled into stomach of mice, and one hour later, 2 mg/kg LPS was instilled into trachea of mice in ER+PLS group to induce lung injury. Twenty-four hours later, bronchoalveolar lavage fluid (BALF) and lung tissue of mice in four groups were collected. HE staining were used for evaluating pathological changes of lung injury. Lung wet/dry weight ratio, protein concentrations and total cell numbers in the BALF were measured to determine the degree of pulmonary edema. Immunohistochemical staining and Western Blot were used for testing the protein expression of SP-A, Data of multiple groups were analyzed by one way variance (ANOVA) and inter-group comparisons were made by the least significant difference (LSD) tests. Results There was no significant difference in lung injury score (LIS) between control group (0.056±0.008) and ER (0.064±0.037) group, The LIS in LPS group (0.846±0.047) was higher than that in control group, however the LIS in ER+LPS group (0.279±0.020) was significant lower than that in LPS group (P < 0.05). Lung wet/dry weight, SP-A concentration and total cell numbers in the bronchoalveolar lavage fluid revealed that the degree of pulmonary edema in LPS group was higher than that in control group, and this pulmonary edema was reversed by erlotinib treatment. Immunohistochemical staining and Western blot showed that the expression of SP-A in LPS group was decreased compared with control group, but it was recovered after erlotinib treatment (P < 0.05). Conclusions Erlotinib could protect the LPS-induced ALI, and it may be related to the regulation of SP-A. Key words: Acute lung injury; Mice; Lipopolysaccharide; Erlotinib; Alveolar epithelial cells; Surfactant protein A; Inflammatory response; Epidermal growth factor receptor; Drug treatment