薑黃素可藉由阻斷腫瘤壞死因子－阿伐與干擾素-6的表現抑制放射線導致的小鼠肺損傷

Curcumin Inhibits Radiation-induced Lung Injury Via Suppression of Radiation-Increased TNF-α and IL-6 Expression in Mice

李昆暻(Kun-Ching Li) ； 劉育昌(Yu-Chang Liu) ； 蔣宜蒼(I-Tsang Chiang) ； 陳信雄(Hsin-Hsiung Chen) ； 林松水(Song-Shei Lin)

《中華放射線技術學雜誌》 38卷4期 (2014/12) Pp. 188-195

摘要

肺癌為世界常見的惡性癌，放射治療是臨床治療肺癌的重要方式之一，但放射線造成正常肺組織的損傷會影響治療效果。因此開發輻射保護劑是十分重要。放射線造成的肺部損傷包含了肺炎和肺纖維化。但發炎激素腫瘤壞死因子－阿伐（tumor necrosis factor-alpha ,TNF-α）和干擾素-6（lnterl eukin-6, IL-6）參與調節放射性肺炎和肺纖維化的發生，而抑制TNF-α和IL-6的表現可以降低放射線對小鼠肺組織的傷害。薑黃素是從鬱金根部所萃取出的多酚類物質，被指出可以增加抗氧化作用而抑制放射線造成小鼠肺部纖維化。然而，薑黃素降低放射線對肺組織的傷害是否與抑制放射線增加TNF-α和IL-6蛋白表現有關，這是不清楚地。本研究的目的是利用小鼠模式評估薑黃素對放射線誘導肺損傷的影響和相關機制。小鼠被隨機分成四組：控制組、薑黃素組（70 mg/kg/day）、放射線組（12 Gy）、合併組。研究中我們利用治療計畫確定每隻小鼠全肺的放射劑量和劑量分佈，用免疫組織化學染色法（immunohistochemistry; IHC）評估薑黃素、放射線、和薑黃素合併放射線對小鼠肺組織中TNF-α和IL-6蛋白表現的影響。細胞凋亡可以反應放射線誘導肺損傷的程度，本研究使用IHC評估肺組織中但凋亡蛋白Caspase-3的活性表現。結果顯示薑黃素可以顯著性抑制放射線誘導TNF-α、IL-6蛋白和Caspase-3的活性表現。建議薑黃素可以藉由降低放射線增加TNF-α和IL毛的蛋白表現，進而減少放射線誘導肺組織損傷。

關鍵字

薑黃素 ； 放射線誘導肺損傷 ； 腫瘤攘死因子-阿伐 ； 干擾素-6

並列摘要

Lung cancer is the most common malignancy in the world. Radiotherapy is an important therapeutic strategy for lung cancer, but the therapeutic efficacy is limited by radiation-induced pulmonary injuries (RIPIs). Therefore, the development of radioprotector may be helpful for patients with lung cancer to reduce RlPIs during radiotherapy course. Rl PIs have two components: pneumonitis and fibrosis. Pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) can modulate radiation-induced pneumonitis and fibrosis, and inhibition of TNF-αand IL-6 can decrease RIPIs. Curcumin, a polyphneol which was extracted from Curcuma longa has been shown to increase antioxidant defenses in lungs and ameliorat radiation-induced pulmonary fibrosis in mice. However, whether curcumin can decrease radiation-induced lung injury via suppression ofradiation-elicited TNF-αand IL-6 expression is ambiguous. The study goal is to investigate the effects and mechanism of curcumin on radiation-induced lung injury in mice. Mice were randomly divided into four groups: control, curcumin (70 mg/kg/day) alone, radiation (12 Gy) alone and combination treatments. The treatment planning system(Xio®) was used to accurately calculate the radiation dose and ensure dose distribution of lung in mice. The effects of curcumin, radiation, and combination of both on TNF-αand IL-6 protein expression in lung tissues were evaluated with immunohistochemistry (IHC) stain. The degree of radiation-induced lung injury can be measured by apoptosis. We also determined pro-apoptotic protein caspase-3 activation in lung tissues. The results indicated that curcumin significantly decreased radiation-induced TNF-αand IL-6 protein expression, and also caspase-3 activation in lung tissues. It suggested that curcumin as radioprotector reduces radiation-induced lung injury via suppression of radiation-elicited TNF-αand IL-6protein expression in mice.

並列關鍵字

Curcumin ； Radiation-induced lung injury ； TNF-α ； IL-6