摘 要: 目的 探讨白藜芦醇对矽肺大鼠肺纤维化及壳多糖酶3样蛋白1(chitinase-3-like protein 1,CHI3L1)表达的影响。方法 选取雄性SPF级SD大鼠24只,随机分为对照组、模型组、白藜芦醇(resveratrol,Res)50 mg/kg和100 mg/kg组。模型组和Res组采用一次性非暴露气管法灌注SiO2混悬液1 ml(50 mg/ml),对照组同法灌注1 ml生理盐水。造模28 d后Res组经口灌胃Res,1次/d,持续28 d;对照组、模型组正常饲养至56 d;处死大鼠。计算大鼠肺脏器系数;采用HE和Masson染色法观察各组大鼠肺组织形态学变化,检测肺组织羟脯氨酸(HYP)、白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、转化生长因子-β1(TGF-β1)、胶原蛋白I(Col-I)、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)、钙黏蛋白E(E-Cad)和CHI3L1的表达水平。结果 与对照组相比,模型组肺脏器系数增加,肺组织出现大面积炎性浸润和纤维化,肺组织中HYP含量、IL-1β、TNF-α、TGF-β1、Col-I、α-SMA、Vimentin、CHI3L1蛋白表达水平均明显升高(P<0.05),E-Cad显著降低(P<0.05)。与模型组相比,染尘56 d后Res组肺泡炎症和纤维化评分、HYP含量、IL-1β、TNF-α、Col-I表达水平均降低(P<0.05);100 mg/kg Res组肺脏器系数、TGF-β1、CHI3L1、Vimentin及α-SMA的表达水平降低(P<0.05),E-Cad显著升高(P<0.05),提示Res干预可明显改变上述指标的变化。结论 白藜芦醇可降低大鼠肺组织CHI3L1的表达,减轻胶原沉积以及上皮间质转化(EMT),从而延缓矽肺纤维化的进展。 |
关键词: 矽肺 壳多糖酶3样蛋白1(CHI3L1) 肺纤维化 白藜芦醇(Res) |
中图分类号: R135.2
文献标识码: A
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基金项目: 山东省自然科学基金(编号:ZR2022MH293);国家科技重大专项(新药创制重大专项)分题(编号:2018ZX09711001-011);山东省医学科学院医药卫生创新工程;山东省中医药科技发展计划(编号:2021M153);山东第一医科大学学术提升计划(编号:2019QL001);济南市科技局临床医学科技创新计划(编号:202019109,201907098) |
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Effects of resveratrol on pulmonary fibrosis and chitinase-3-like protein 1 expression in silicosis-rats |
QUAN Yifan,TANG Qiong,XING Chen,LIU Fang,LI Ming,LI Chao,JIA Qiang,BO Cunxiang,ZHANG Zhenling,CHEN Shangya
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Shandong First Medical University/Shandong Academy of Medical Sciences/Shandong Academy of Occupational Health and Occupational Medicine,Jinan,Shandong 250000,China
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Abstract: Objective To investigate the effects of resveratrol on lung fibrosis and chitinase-3-like protein 1(CHI3L1)expression in rats with silicosis. Methods Twenty-four male SPF grade SD rats were randomly divided into control group,model group,resveratrol groups(50,100 mg/kg),model group and resveratrol groups,were given non-exposed tracheal infusion of silicon dioxide(SiO2)suspension solution of 1 ml(50 mg/ml),and the control group received 1 ml of normal saline. After 28 days of modeling,the rats were given oral administration of resveratrol once a day for 28 days,the control group and model group were normally raised for 56 d,and then were killed. The coefficient of lung organs was calculated,and the morphological changes of lungs were observed by HE and Masson staining,and the expression levels of hydroxyproline(HYP),interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),transforming growth factor-β1(TGF-β1),type I collagen(Col-I),αsmooth muscle actin(α-SMA),Vimentin,epithelia-Cadherin(E-Cad)and CHI3L1 were detected. Results Compared with the control group,after 56 days of dust contamination,the lung coefficient of the model group increased,and a large area of inflammatory infiltration and fibrosis appeared in the lung tissue. The levels of HYP,IL-1β,TNF-α,TGF-β1,Col-I,α-SMA,Vimentin and CHI3L1 in lung tissues were significantly increased(P<0.05),and E-Cad was decreased significantly(P<0.05). Compared with the moder group,the alveolar inflammation and fibrosis score,HYP content,IL-1β,TNF-αand Col-I expression levels of resveratrol group were reduced after 56 days of dust exposure(P<0.05). Moreover,in the resveratrol(100 mg/kg)group,the lung coefficient,the levels of TGF-β1,CHI3L1,Vimentin andα-SMA in lung tissue were decreased(P<0.05),and E-Cad was increased signficantly(P<0.05),it suggests that resveratrol reversed the changes of the above indices. Conclusion Resveratrol can reduce the expression of CHI3L1 in rat lung tissue,reduce collagen deposition and EMT process,thereby delay the development of silicosis fibrosis. |
Keywords: silicosis chitinase-3-like protein 1(CHI3L1) pulmonary fibrosis resveratrol(Res) |