染料木黄酮对辐射损伤小鼠肺纤维化的防护作用

Genistein protects mice against radiation-induced pulmonary fibrosis

目的探讨染料木黄酮(genistein,GEN)对小鼠放射性肺纤维化(radiation-induced pulmonary fibrosis,RIPF)的保护作用。方法 60只8周龄C57BL/6J雌性小鼠,随机分为对照组(C组)、单纯照射组(R组)、染料木黄酮+照射组(Gen+R组)和氨磷汀(Amifostine)+照射组(Ami+R组)(n=10)。除对照组外,其余各组小鼠接受8MV X线全胸照射(12.0±0.2)Gy。Gen+R组于照射开始前24、16、8 h皮下注射GEN 200 mg/kg,Ami+R组于照射开始前30 min皮下注射氨磷汀100 mg/kg,照射后每天1次连续给药4周。照射后4、8、12周,HE染色观察肺组织病理改变,ELISA方法测定血清中的TGF-β1的含量,比色法测定肺组织羟脯氨酸的含量。结果病理检测显示照射后时间越长,放射性肺损伤小鼠肺纤维化越重,染料木黄酮能减轻肺组织炎症及纤维化;照射后小鼠血清TGF-β1和肺组织羟脯氨酸的含量也呈递增趋势,染料木黄酮能降低TGF-β1和羟脯氨酸的含量(P<0.05),尤其是照射前24 h给予染料木黄酮能达到与氨磷汀类似的疗效。结论染料木黄酮可减轻肺组织的纤维化,具有明显的辐射防护作用。

Objective To evaluate the effect of genistein as a protecting agent on the radiation- induced pulmonary fibrosis in mice. Methods The thoraces of female 8-week-old C57BL/6J mice were exposed to either sham irradiation or single fraction of 8MV X ray radiation of （12.0 ±0.2） Gy. A total of 60 mice were divided as Sham （C group, n =10）, radiation （R group, n = 10）, genistein ＋ radiation （Gen ＋ R group, n =30） , amifostine ＋ radiation （Ami ＋ R group, n = 10）. The mice of Gen ＋ R group were adminis- tered with genistein （200 mg/kg） in 8, 16 and 24 h respectively before irradiation （n = 10） and then adminis- tered once per day until 4 weeks. While the mice of Ami ＋ R group was injected subcutaneously by 100 mg/kg amifostine in 30 min before irradiation and in every day until 4 weeks. Mice were sacrificed at 4, 8, and 12 weeks post-irradiation. The lung tissues were removed and processed for definitive analysis, including hydroxypmline content and HE staining. ELISA was used to measure the serum level of transforming growth factor 131 （TGF-β1）. Results Pathological study showed that pulmonary fibrosis became more severe along with the time after irradiation, and genistein attenuated lung inflammation and fibrosis. Radiation increased the expression of TGF-β1 and hydroxyprolin content in lung tissue in a time-dependent manner, and genistein reduced TGF-β1 expression and hydroxyprolin content （ P 〈 0.05 ）. Conclusion Genistein attenuates the progress of radiation-induced lung fibrosis, and exerts significant effect on prevention against radiation.