白藜芦醇对博来霉素诱导小鼠肺间质纤维化保护机制的研究

Study on the Protective Mechanism of Resveratrol Against Bleomycin In⁃duced Pulmonary Interstitial Fibrosis in Mice

目的探究白藜芦醇对博来霉素诱导小鼠肺间质纤维化的抗纤维化作用并阐明其潜在机制。方法2023年2—9月在齐齐哈尔医学院附属第三医院动物实验中心将购买的30只8周龄雄性C57BL/6小鼠采用随机数字表法分为3组,对照组,模型组和干预模型组,每组10只,对照组小鼠正常饲养,模型组和干预模型组均给予博来霉素制备肺纤维化动物模型,模型建立成功后干预模型组给予白藜芦醇灌胃,干预组和对照组给予等体积生理盐水灌胃,治疗4周后比较肺泡炎症、肺纤维化程度评分、肺组织中肿瘤坏死因子α(tu⁃mor necrosis factor-α,TNF-α)、白介素1β(interleukin 1β,IL-1β)、白介素6(interleukin 6,IL-6)、前列腺素(prostaglandin,PG)、还原型谷胱甘肽(glutathione,GSH)、羟脯氨酸(hydroxyproline,HYP)、丙二醛(malondialde⁃hyde,MDA)、超氧化物歧化酶(superoxide dismutase,SOD)水平,以及肺组织中转化生长因子β1(transforming growth factor beta 1,TGF-β1)、Samd3、细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK1/2)蛋白表达情况。结果模型干预组肺泡炎症和肺纤维化程度评分分别为(1.40±0.65)分、(1.90±0.57)分,均低于模型组的(3.20±0.74)分、(3.80±0.72)分,差异有统计学意义(t=5.779、6.543,P均<0.05)。与对照组比较,模型组TNF-α、IL-1β、IL-6、PG、HYP、MDA表达水平,以及TGF-β1、Samd3、ERK1/2蛋白表达均较高,差异有统计学意义(P均<0.05);SOD、GSH表达水平降低,差异有统计学意义(P均<0.05);与模型组比较,干预模型组TNF-α、IL-1β、IL-6、PG、HYP、MDA表达水平,以及TGF-β1、Samd3蛋白水平降低,差异有统计学意义(P均<0.05);SOD、GSH表达水平增高,差异有统计学意义(P均<0.05);但ERK1/2蛋白表达变化不明显,差异无统计学意义(P>0.05)。结论白藜芦醇通过调节TGF-β1/Smad3通路发挥抗肺纤维化作用。

Objective To investigate the anti fibrotic effect of resveratrol on bleomycin induced pulmonary interstitial fibrosis in mice and elucidate its potential mechanism.Methods From February to September 2023,thirty eightweek-old male C57BL/6 mice were purchased and housed in the Animal Experiment Center of the Third Affiliated Hospital of Qiqihar Medical University.The mice were randomly divided into three groups using a random number table:control group,model group,and intervention model group,with ten mice in each group.The control group was fed normally,while the model and intervention model groups were administered bleomycin to establish a pulmonary fi⁃brosis animal model.After successful model establishment,the intervention model group received resveratrol via ga⁃vage,while the control and model groups were given an equal volume of normal saline via gavage.After 4 weeks of treatment,compared alveolar inflammation,pulmonary fibrosis scores,and levels of tumor necrosis factor-α(TNF-α),interleukin 1β(IL-1β),interleukin 6(IL-6),prostaglandin(PG),glutathione(GSH),hydroxyproline(HYP),malondial⁃dehyde(MDA),superoxide dismutase(SOD),as well as the expression levels of TGF-β1,Smad3,and ERK1/2 pro⁃teins in lung tissue.Results The scores of alveolar inflammation and pulmonary fibrosis in the model intervention group were 1.40±0.65 and 1.90±0.57,which were lower than those in the model group 3.20±0.74 and 3.80±0.72,and the differences were statistically significant(t=5.779,6.543,both P<0.05).Compared with the control group,the ex⁃pression levels of TNF-α,IL-1β,IL-6,PG,HYP and MDA,as well as the expression levels of TGF-β1,Samd3 and ERK1/2 proteins in the model group were higher,and the differences were statistically significant(all P<0.05).The ex⁃pression levels of SOD and GSH were decreased,and the differences were statistically significant(both P<0.05).Com⁃pared with the model group,the expression levels of TNF-α,IL-1β,IL-6,PG,HYP and MDA,and the levels of TGF-β1 and Samd3 protein in the intervention model group were decreased,and the differences were statistically sig⁃nificant(all P<0.05).There were statistically significant differences in the expression levels of SOD and GSH(both P<0.05).However,ERK1/2 protein expression did not change significantly,and the difference was not statistically sig⁃nificant(P>0.05).Conclusion Resveratrol exerts anti pulmonary fibrosis effects by regulating the TGF-β1/Smad3 pathway.