摘要
目的探讨丁苯酞对小鼠肺纤维化的基质金属蛋白酶及Bax/Bcl-2表达的影响。方法将72只雄性C57BL/6小鼠作为研究对象,随机分为丁苯酞组、模型组、正常对照组三组,每组各24只。除对照组外,其余两组以博来霉素为诱导剂诱导小鼠肺纤维化。丁苯酞治疗组予丁苯酞180 mg/kg(实验专用玉米油稀释)干预,其余两组予实验专用玉米油10 ml/kg灌胃,每天1次,连续灌胃14天和28天。分别于末次给药24 h后处死,对应各组小鼠12只测定肺组织羟脯氨酸(HYP)、总抗氧化力(T-AOC)、Bax、Bcl-2、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶抑制剂-1(TIMP-1)水平,并进行肺组织病理学检查。结果与模型组相比,丁苯酞治疗组给药14天和28天后其肺组织中HYP、Bax、MMP-9、TIMP-1水平显著降低(P<0.05),Bcl-2、T-AOC含量明显升高(P<0.05);与丁苯酞治疗组给药14天相比,Bcl-2水平与28 d的水平无显著差异(P>0.05),给药28 d的肺组织中HYP、Bax、MMP-9、TIMP-1水平显著降低(P<0.05),T-AOC含量明显升高(P<0.05),且MMP-9/TIMP-1比值更趋于平衡。结论丁苯酞对博来霉素诱导小鼠肺纤维化有一定的治疗作用,其机制可能是丁苯酞通过选择性地调节细胞中Bax/Bcl-2的表达,降低MMP-9、TIMP-1含量,调节MMP-9/TIMP-1比值,提高抗氧化能力等,从而实现其治疗作用。
Objective To investigate the effect of butyphthalide on matrix metalloproteinase and Bax/Bcl-2 expression in mice with pulmonary fibrosis.Methods 72 male C57 BL/6 mice were randomly divided into 3 groups including normal control group,model group,and butyphthalide group,24 in each group.Except the control group,bleomycin was used to induce pulmonary fibrosis in mice in the other two groups.Butyphthalide group was treated with butyphthalide for intervention at the dose of 180 mg/kg(corn oil was used as dilution).And the other two groups were intragastric administrated corn oil at the dose of 10 ml/kg,once a day,continuous for 14 d and 28 d.The levels of lung tissue hydroxyproline(HYP),total antioxidant capacity,Bax,Bcl-2,matrix metalloproteinase-9(MMP-9),matrix metalloproteinase inhibitor-1(TIMP-1)were measured in 12 mice of each group 24 h after the last administration,And lung tissues was collected for histopathological examination.Results Compared to the model group,the levels of HYP,Bax,MMP-9,TIMP-1 in lung tissue of butyphthalide group decreased significantly after 14 d and 28 d(P<0.05).The concentration of Bcl-2 and T-AOC increased significantly(P<0.05).Compared with the results at 14 d in butyphthalide treatment group,HYP,Bax,MMP-9,and TIMP-1 levels in lung tissue decreased significantly on 28 d(P<0.05),while the level of Bcl-2 didn’t changed significantly(P>0.05),the MMP-9/TIMP-1 ratio tended to be more balanced(P<0.05).The T-AOC content increased significantly(P<0.05).Conclusions Butyphthalide has a certain therapeutic effect on bleomycin induced pulmonary fibrosis in mice.The mechanism may be that butyphthalide selectively regulates the expression of Bax/Bcl-2 in cells,reduces MMP-9 and TIMP-1 content,regulates MMP-9/TIMP-1 ratio,improve antioxidant ability and so on,to achieve its therapeutic effect.
作者
张林
白俐
邓海娟
黄桑
邓群
ZHANG Lin(Department qf critical care medicine,Guangzhou Xinhai hospital,Guangzhou,Guangdong,510300,China)
出处
《齐齐哈尔医学院学报》
2020年第24期3041-3045,共5页
Journal of Qiqihar Medical University
基金
广州市海珠区科技计划项目(海科工商信计2018-92)。
