橘皮苷对百草枯致肺纤维化小鼠细胞外基质转化干预作用及Fas/FasL蛋白表达的机制研究  

Analysis of the intervention eff ect of hesperidin on the extracellular matrix transformation in mice with pulmonary fi brosis induced by paraquat and the mechanism of Fas/FasL protein expression

作　　者：陈宏 张佩颖[2] 赵建云 王文增 张明浩 李可心 邓琳千 宋倩男 CHEN Hong;ZHANG Peiying;ZHAO Jianyun;WANG Wenzeng;ZHANG Minghao;LI Kexin;DENG Linqian;SONG Qiannan(Heilongjiang Provincial Academy of Traditional Chinese Medicine,Harbin 150036,China;Department of Pediatrics,the First Affiliated Hospital of Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江省中医药科学院,哈尔滨150036 [2]黑龙江中医药大学附属第一医院儿科,哈尔滨150040

出　　处：《吉林中医药》2021年第5期654-658,共5页Jilin Journal of Chinese Medicine

基　　金：中国博士后科学基金第13批特别资助(2020T130178);黑龙江省博士后启动资金;黑龙江省中医药科研项目(ZHY19-004)。

摘　　要：目的探讨橘皮苷对百草枯致肺纤维化小鼠细胞外基质转化的干预作用及Fas/FasL蛋白表达的机制。方法将60只雄性昆明小鼠随机分为空白组(Blank组)、模型组(Model组)、橘皮苷高剂量HES(H)组、橘皮苷中剂量HES(M)组、橘皮苷低剂量HES(L)组和地塞米松(DEX)组,每组10只。制备小鼠肺纤维化模型的同时ig给药,Blank组和Model组ig 0.1 mL 0.9%生理盐水,每2天给药1次,第28天眼球取血后处死所有小鼠,肺组织HE及Masson病理学染色,对比各组之间炎症浸润及纤维化变化,用免疫组织化学法检测肺组织Fas/FasL的表达情况。利用双荧光素酶报告基因实验检测药物对EMT-like标志物(E-Cadherin,Vimentin),MMP2,NF-κB等的影响。结果模型组小鼠的肺组织严重破坏,肺泡结构消失,大量纤维组织增生;与肺纤维化模型组相比,给药橘皮苷组小鼠的肺组织肺纤维化程度明显改善,肺泡结构相对更加完整。与模型组相比,HES(H)组、HES(M)组、HES(L)组和DEX组Fas/FasL表达显著降低(P<0.01)。与HES(M)组、HES(L)组和DEX组相比,HES(H)组Fas/FasL表达也显著降低(P<0.05),橘皮苷可以抑制EMT-like过程,增加MMP2的表达,抑制NF-κB的表达(均P<0.05),肺纤维化及肺炎症浸润程度明显减轻。结论橘皮苷对于百草枯导致的小鼠肺纤维化具有保护作用,降低Fas/FasL表达,橘皮苷对百草枯致肺纤维小鼠纤维化改善与Fas/FasL凋亡通路有关。Objective To investigate the intervention effect of hesperidin on the transformation of extracellular matrix in mice with pulmonary fibrosis induced by paraquat and the mechanism of Fas/FasL protein expression.Methods Sixty male Kunming mice were randomly divided into blank group(Blank group),model group(Model group),hesperidin high-dose group(H),hesperidin medium-dose group(M),and hesperidin low-dose group(L)and dexamethasone group(DEX),with 10 mice in each group.While preparing the mouse pulmonary fibrosis model,administration was performed.Blank group and Model group were given 0.1 mL 0.9%saline,once every 2 days.On the 28th day,all mice were killed after eyeball blood was sampled.He and Masson pathological staining of lung tissue were used to compare the infl ammatory infi ltration and fibrosis changes among the groups.The expression of Fas/FasL in lung tissue was detected by immunohistochemistry.The double luciferase reporter gene assay was used to detect the eff ects of drugs on EMT-like markers(E-Cadherin,Vimentin),MMP2,NF-κB,etc.Results The lung tissues of the mice in the model group were severely damaged as the alveolar structure disappeared and a large amount of fibrous tissue proliferated.Compared with the model group,the lung fibrosis of the mice in the H group was signifi cantly improved,and the alveolar structure was relatively more complete.Compared with the model group,the expression of Fas/FasL in the H group,M group,L group and DEX group was signifi cantly reduced(P<0.01).Compared with the M group,L group and DEX group,the expression of Fas/FasL in the H group was also signifi cantly reduced(P<0.05).Hesperidin inhibited the EMT-like process and increased the expression of MMP2,inhibited the expression of NF-κB(all P<0.05),and the degree of pulmonary fibrosis and pneumonia infi ltration was signifi cantly reduced.Conclusion Hesperidin has a protective eff ect on paraquat-induced lung fibrosis in mice,reducing the expression of Fas/FasL.The improvement of hesperidin on paraquat-induced pulmonary

关 键 词：橘皮苷 百草枯 小鼠肺纤维化 

分 类 号：R285.5[医药卫生—中药学]