摘 要: 目的 探讨白藜芦醇(resveratrol,Res)抑制JAK2/STAT3信号通路对矽肺大鼠纤维化的干预作用。方法 将无特定病原体级的Sprague Dawley雄性大鼠24只按随机数字表法分为对照组(生理盐水)、模型组(SiO2)和Res(50、100 mg/kg)组,每组6只。模型组和Res组经气管一次灌注1 ml(50 mg/ml)SiO2混悬液,对照组灌注1 ml生理盐水。造模24 h后,每天给药1次,Res组分别经口灌胃50、100 mg/kg,对照组和模型组给予等体积的1%的羧甲基纤维素钠。28 d后处死大鼠收集肺组织,计算肺脏器系数,观察肺组织病理学变化,检测羟脯氨酸(HYP)、白介素-18(IL-18)、白介素-1β(IL-1β)、转化生长因子-β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)、胶原蛋白Ⅰ(Col-Ⅰ)、α平滑肌肌动蛋白(α-SMA)、E-钙黏蛋白(E-Cad)、波形蛋白和JAK2/STAT3的表达水平。结果 与对照组相比,模型组的肺脏器系数、肺组织病理Szapiel评分、HYP含量和IL-18、IL-1β、TGF-β1、TNF-α水平均明显升高(P<0.05),而Res抑制了这些指标的表达(P<0.05)。蛋白免疫印迹结果显示,模型组Col-Ⅰ、α-SMA、波形蛋白和JAK2/STAT3的蛋白表达高于对照组,E-Cad的表达低于对照组(P<0.05);Res组Col-Ⅰ,α-SMA、波形蛋白和JAK2/STAT3的蛋白表达水平降低,E-Cad的表达升高(P<0.05)。实时定量反转录聚合酶链反应实验(RT-PCR)结果显示,模型组JAK2/STAT3的mRNA表达高于对照组,Res组JAK2/STAT3的mRNA表达显著低于模型组(P<0.05)。结论 Res能有效减轻矽肺大鼠肺部炎症和纤维化,可能与其抑制了JAK2/STAT3信号通路、影响炎性因子分泌有关。 |
关键词: 白藜芦醇 矽肺 JAK2/STAT3信号通路 纤维化 |
中图分类号: R135.2
文献标识码: A
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基金项目: 国家科技重大专项(新药创制大专项)分题(编号:2018ZX0971100-011);山东省医学科学院医药卫生创新工程;山东第一医科大学学术提升计划(2019QL001);济南市科技局临床医学科技创新计划(202019109) |
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Resveratrol interferes with progress of silicosis by inhibiting JAK2/STAT3 signal pathway |
TANG Qiong,LI Ming,XING Chen,LIU Fang,QUAN Yi-fan,JIA Qiang,BO Cun-xiang,ZHANG Zhen-ling
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Shandong First Medical University/Shandong Provincial Academy of Medical Sciences/Shandong Provicial Academy of Occupational Health and Occupational Medicine,Jinan,Shandong 250000,China
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Abstract: Objective To investigate the interventional effect of resveratrol (Res) inhibition on fibrosis in silicosis rats by inhibiting the JAK2/STAT3 signaling pathway. Methods Twenty-four Sprague Dawley male rats without pecific pathogens level were divided into control group, silica model group and Res 50 mg/kg group, Res 100 mg/kg group by the random number table method, six rats in each group. The rats of model group and Res administration groups were treated with single instillation of 1 ml silica suspension (contained 50 mg SiO2) via trachea, the controls only be perfused with 1 ml of saline through trachea. After 24 hours of modeling, the rats of Res treated groups were administered 50 mg/kg and 100 mg/kg once daily by oral gavage, and an equal volume of 1% carboxymethylcellulose sodium was given for rats of control and model groups in the same way. Twenty-eight days later, all the rats were killed, the lung tissues were collected for calculation of lung coefficients, examination of pathological changes, and detection of expression levels of hydroxyproline (HYP), interleukin-18 (IL-18), interleukin-1β (IL-1β), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), collagen typeⅠ(Col-Ⅰ), α-smooth muscle actin (α-SMA), epithelia-Cadherin (E-Cad), Vimentin, and JAK2/STAT3 in lung tissues. Results The results showed that the lung coefficient, the Szapiel score, the HYP content, and the levels of IL-18, IL-1β, TGF-β1, and TNF-α were all significantly rose in model group compared with control group (P<0.05), whereas Res might significantly inhibite the changes of these indicators (P<0.05). The Western blot analysis showed that the protein expressions of Col-Ⅰ, α-SMA, Vimentin and JAK2/STAT3 of model group were significantly higher than that of control group, the expression of E-Cad was lower than that of control group (P<0.05). The expressions of Col-Ⅰ, α-SMA, Vimentin and JAK2/STAT3 of Res group were decreased, while the expression of E-Cad was increased (P<0.05). The result of RT-PCR showed that the mRNA expression of JAK2/STAT3 of model group was higher than that of control group, and the mRNA expression of JAK2/STAT3 of Res group was also lower than that of model group (P<0.05). Conclusion The results suggested that Res might effectively alleviate lung inflammation and fibrosis in rats with silicosis, which may be related to its inhibition effect on JAK2/STAT3 signaling pathway thereby affects the secretion of inflammatory factors. |
Keywords: resveratrol(Res) silicosis JAK2/STAT3 signal pathway fibrosis |