The protective effect of geranylgeranylacetone-induced heat shock protein 70 on radiation-induced lung injury in mice / 肿瘤

ABSTRACT

Objective: To study whether the expression of heat shock protein 70 (HSP70) in lung tissue induced by GGA (geranylgeranylacetone) has a protective effect on radiation-induced lung injury in mice and its possible mechanism. Methods: One hundred and four health KM mice were randomly divided into control group, GGA group, radiation group and GGA combined with radiation group. Of GGA group and the GGA combined with radiation group before irradiation, the mice were pretreated with GGA at a dose of 600 mg·kg-1·d -1 for 3 d, while the mice of the control and the radiation groups were given 0.9% sodium chloride solution. Then the mice in the radiation group and the GGA combined with radiation group received whole-lung irradiation with X-ray at a single fraction of 20 Gy, while the mice of the other two groups received sham-irradiation. After irradiation, all the mice continued receiving treatment until the appropriate time points for detection. The expressions of HSP70 mRNA and TNF-α (tumor necrosis factor alpha) mRNA in lung tissues were detected by RT-PCR at day 1 and day 3 after irradiation. The positive cells and the distribution of HSP70 proteins were evaluated by immunohistochemistry at day 1 after irradiation. The morphological changes of lung tissues were observed by hematoxylin and eosin staining at day 3 and day 60 after irradiation. The pulmonary fibrosis severity was evaluated by Masson's trichrome staining and hydroxyproline content at day 60. The serum TGF-β1 (transforming growth factor- beta1) level at each time point was measured by ELISA. Results: The typical early stage radiation pneumonitis and the late pulmonary fibrosis were observed in mice in the radiation group. In mice treated by GGA and radiation, HSP70 expression level of the lung tissues was higher than that in the control group or the radiation group. TNF-α mRNA level, serum TGF-β1 level, the severities of radiation pneumonitis and pulmonary fibrosis, and the content of hydroxyproline in the GGA combined with radiation group were lower than those in the radiation group (P < 0.05). There was no significant difference between the GGA group and the control group for all indices. Conclusion: The expression of HSP70 in mice lung tissues induced by regular oral administration of GGA can protect against radiationinduced lung injury, which may be related to the inhibition of expressions of important inflammatory factor TNF-α and fibrosis-related factor TGF-β1. Copyright © 2012 by TUMOR.