柚皮素通过调控TGF-β1/smad通路抑制肝纤维化  

The protective effects of naringenin on liver fibrosis by regulating TGF-β1/smad pathway

作　　者：岳杉杉 彭安康 马泽江 祁荣 YUE Shan-shan;PENG An-kang;MA Ze-jiang;QI Rong(School of Basic Medical Science, Shihezi University, Shihezi Xinjiang 832000, China;Dept of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China)

机构地区：[1]石河子大学医学院,新疆石河子832000 [2]北京大学医学部基础医学院药理学系,北京100191

出　　处：《中国药理学通报》2022年第2期248-254,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No U1803125)。

摘　　要：目的研究柚皮素(naringenin,NGN)对小鼠肝纤维化的抑制作用及机制。方法TGF-β1孵育LX2细胞24 h,构建体外纤维化模型,NGN(100、200μmol·L^(-1))处理细胞;喂饲8~10周龄雄性C57BL/6小鼠蛋氨酸-胆碱缺乏饲料6周,诱导小鼠肝脏纤维化模型,同时灌胃给予NGN(100 mg·kg^(-1)),研究NGN抑制肝纤维化的作用及机制。qRT-PCR检测α-SMA、col1和col3的基因水平;Western blot检测α-SMA、col1、TGF-β1、p-smad2和p-smad3的蛋白水平;HE染色和天狼猩红染色分别检测小鼠肝脏组织形态和纤维化程度。结果体内外实验均表明,与模型组相比,NGN处理明显降低了α-SMA、col1和col3的mRNA和蛋白表达水平,同时明显抑制TGF-β1/smad通路的激活。HE染色和天狼猩红染色结果同样表明,NGN处理与模型组相比明显降了MCD饲料诱导的肝脏纤维化程度。结论NGN可明显抑制TGF-β1诱导的LX2细胞纤维化及蛋氨酸-胆碱缺乏饲料诱导的小鼠肝纤维化,机制与其抑制TGF-β1/smad通路激活有关。Aim To study the effects of naringenin on MCD diet-induced liver fibrosis and its related mechanisms.Methods LX2 cells were incubated with TGF-β1 for 24 h to establish the in vitro fibrosis model.LX2 cells were treated with NGN at the same time.Male C57BL/6 mice were fed with MCD diet for six weeks to induce liver fibrosis.100 mg·kg^(-1)·d^(-1) NGN was administered by gavage simultaneously.The protein expressions ofα-SMA,col1,TGF-β1,p-smad2 and p-smad3 were evaluated by Western blot.The mRNA expressions ofα-SMA,col1 and col3 were detected by qRT-PCR.The degree of liver fibrosis was evaluated by Sirius red staining.Results Both in in vivo and in vitro experiments,compared with model group,the mRNA levels ofα-SMA,col1 and col3 and protein levels ofα-SMA,TGF-β1,p-smad2 and p-smad3 significantly decreased in NGN treatment group.The results of HE staining and Sirius red staining also indicated that NGN significantly decreased liver fibrosis induced by MCD diet.Conclusions Naringin can significantly inhibit liver fibrosis induced by MCD diet,which may be related to TGF-β1/Smad pathway.

关 键 词：柚皮素 肝脏纤维化 蛋氨酸-胆碱缺乏饲料 肝星状细胞 TGF-Β1 TGF-β1/smad通路 

分 类 号：R-332[医药卫生] R284.1