莪术油通过抑制铁死亡减轻博来霉素诱导的小鼠肺纤维化的机制研究  

Mechanism of Zedoary Turmeric Oil on attenuating bleomycin-induced pulmonary fibrosis in mice through inhibition of ferroptosis

作　　者：王殷彤 王成功 贾思凝 俞文秀 王方岩 姜程曦 程锦国[2] WANG Yin-tong;WANG Cheng-gong;JIA Si-ning;YU Wen-xiu;WANG Fang-yan;JIANG Cheng-xi;CHENG Jin-guo(The Second Affiliated College of Wenzhou Medical University,Wenzhou 325000,China;The First Affiliated College of Wenzhou Medical University,Wenzhou 325000,China;School of Pharmacy,Wenzhou Medical University,Wenzhou 325000,China;School of Basic Medicine,Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第二学院,浙江温州325000 [2]温州医科大学附属第一学院,浙江温州325000 [3]温州医科大学药学院,浙江温州325000 [4]温州医科大学基础医学院,浙江温州325000

出　　处：《中草药》2023年第16期5274-5282,共9页Chinese Traditional and Herbal Drugs

基　　金：温州市新型冠状病毒肺炎疫情防控应急攻关项目(ZY202003)。

摘　　要：目的探究莪术油是否通过抑制铁死亡减轻博来霉素诱导的小鼠肺纤维化及作用机制。方法40只雄性C57BL/6小鼠分为对照组、模型组和莪术油低、高剂量(3.25、13.00 mg/kg)组。小鼠气管插管注射博来霉素(3 mg/kg)制备肺纤维化模型,造模7 d后开始给药,给药组连续14 d隔日ip莪术油。给药结束后,通过各组小鼠体质量和肺干湿质量比评估小鼠一般情况;采用苏木素-伊红(HE)和Masson染色观察肺组织病理变化;检测血清中炎症因子水平和肺组织中羟脯氨酸(hydroxyproline,HYP)、氧化应激水平;Western blotting检测肺组织中肺纤维化和铁死亡相关蛋白表达。结果与模型组比较,莪术油组小鼠体质量增长(P<0.05),肺水肿程度减轻,肺组织损伤情况好转,胶原纤维沉积减少;肺组织氧化产物丙二醛(malondialdehyde,MDA)及HYP水平减少(P<0.05、0.01),还原酶谷胱甘肽(glutathione,GSH)活性增加(P<0.05);血清中炎症因子水平明显降低(P<0.01);肺组织纤维化相关蛋白I型胶原蛋白(collagen I)、α-平滑肌肌动蛋白(α-smooth muscle actin,α-SMA)和波形蛋白(vimentin)表达下调(P<0.05、0.01),谷胱甘肽过氧化物酶4(glutathione peroxidase4,GPX4)蛋白表达上调(P<0.01),转铁蛋白受体1(transferrin receptor 1,TFR1)和二价金属转运蛋白1(divalent metal transporter 1,DMT1)蛋白表达下调(P<0.05、0.01)。结论莪术油能够通过抑制铁死亡,改善氧化应激,抑制炎症水平,减轻博来霉素诱导的小鼠肺纤维化。Objective To explore whether Zedoary Turmeric Oil(莪术油)can alleviate bleomycin induced pulmonary fibrosis in mice by inhibiting ferroptosis and the specific mechanism.Methods A total of 40 C57BL/6 male mice were divided into control group,model group,and Zedoary Turmeric Oil low-and high-dose(3.25,13.00 mg/kg)groups.The model of pulmonary fibrosis was established by injecting bleomycin(3 mg/kg)through tracheal intubation in mice.The drug was administered 7 d after the model was established.The drug group was given Zedoary Turmeric Oil every other day for 14 consecutive days.After administration,the general condition of mice was evaluated by comparing their body weight and lung dry wet weight ratio in each group;Pathological changes of lung tissue was observed by HE and Masson staining;Levels of inflammatory factors in serum and hydroxyproline(HYP)and oxidative stress levels in lung tissue were detected;Western blotting was used to detect the expressions of pulmonary fibrosis and ferroptosis related proteins in lung tissue.Results Compared with model group,the body weight of mice in Zedoary Turmeric Oil group was increased(P<0.05),the degree of pulmonary edema was reduced,the damage of lung tissue was improved,and the deposition of collagen fibers was reduced;The levels of oxidation products malondialdehyde(MDA)and HYP in lung tissue were decreased(P<0.05,0.01),and the activity of glutathione(GSH)was increased(P<0.05);The levels of inflammatory factors in serum were significantly reduced(P<0.01);Expressions of protein associated with pulmonary fibrosis collagen I,α-smooth muscle actin(α-SMA)and vimentin in lung tissue were down-regulated(P<0.05,0.01),glutathione peroxidase 4(GPX4)protein expression was up-regulated(P<0.01),transferrin receptor 1(TFR1)and divalent metal transporter 1(DMT1)protein expressions were down-regulated(P<0.05,0.01).Conclusion Zedoary Turmeric Oil can alleviate bleomycin induced-pulmonary fibrosis in mice by inhibiting ferroptosis,improving oxidative stress and inhibiting inflammatio

关 键 词：肺纤维化 莪术油 铁死亡 氧化应激 炎症因子 

分 类 号：R285.5[医药卫生—中药学]