The Protective Effect Of Geranylgeranylacetoned-induced Heat Shock Protein70on Radiation-induced Lung Injury In Mice

Objective: To study whether the expression of heat shock protein70(HSP70) in lung tissue induced by GGA (geranylgeranylacetone) has aprotective effect on radiation-induced lung injury in mice and its possiblemechanism.Methods: One hundred and four health KM mice were randomlydivided into control group, GGA group, radiation group and GGAcombined with radiation group. Of GGA group and the GGA combinedwith radiation group before irradiation, the mice were pretreated with GGAat a dose of600mg.kg–1.d–1for3d, while the mice of the control and theradiation groups were given0.9%sodium chloride solution. Then the micein the radiation group and the GGA combined with radiation groupreceived whole-lung irradiation with X-ray at a single fraction of20Gy,while the mice of the other two groups received sham-irradiation. Afterirradiation, all the mice continued receiving treatment until the appropriatetime points for detection. The expressions of HSP70mRNA and TNF-α (tumor necrosis factor-alpha) mRNA in lung tissues were detected byRT-PCR at day1and day3after irradiation. The positive cells and thedistribution of HSP70proteins were evaluated by immunohistochemistry atday1after irradiation. The morphological changes of lung tissues wereobserved by hematoxylin and eosin staining at day3and day60afterirradiation. The pulmonary fibrosis severity was evaluated by Masson’strichrome staining and hydroxyproline content at day60. The serumTGF-β1(transforming growth factor-beta1) level at each time point wasmeasured by ELISA.Results: The typical early stage radiation pneumonitis and the latepulmonary fibrosis were observed in mice in the radiation group. In micetreated by GGA and radiation, HSP70expression level of the lung tissueswas higher than that in the control group or the radiation group. TNF-αmRNA level, serum TGF-β1level, the severities of radiation pneumonitisand pulmonary fibrosis, and the content of hydroxyproline in the GGAcombined with radiation group were lower than those in the radiation group(P <0.05). There was no significant difference between the GGA groupand the control group for all indices.Conclusion: The expression of HSP70in mice lung tissues induced byregular oral administration of GGA can protect against radiation-inducedlung injury, which may be related to the inhibition of expressions ofimportant inflammatory factor TNF-α and fibrosis-related factor TGF-β1.