摘要
肝纤维化是不同致病因素引起的肝脏慢性损伤的共同病理过程,是向肝硬化发展的必然阶段。课题组前期研究发现,橙皮苷(HDN)对四氯化碳诱导的化学性肝纤维大鼠具有很好的保护作用。该实验在前期研究的基础上,通过建立体外血小板衍生生长因子(PDGF)诱导的肝星状细胞(HSC)-T6模型,观察HDN对HSC-T6增殖的抑制作用,ELISA法检测HSC-T6上清液中Ⅰ型胶原(Collagen)的含量,RT-PCR技术测定HSC-T6中转化生长因子(TGF)-β1,Smad2,Smad3,Smad7,结缔组织生长因子(CTGF)mRNA的表达,Western blot技术检测HSC-T6中TGF-β1,CTGF蛋白的表达,探讨HDN对HSC中TGF-β1/Smad信号通路的影响及其可能的作用机制。结果显示,PDGF不仅可明显促进HSC-T6增殖与Collagen I的生成,还可显著增加TGF-β1,Smad2,Smad3,CTGF mRNA和TGF-β1,CTGF蛋白的表达;给予HDN干预后,可显著抑制HSC-T6增殖与Collagen I的生成,降低TGF-β1,Smad2,Smad3,CTGF mRNA和TGF-β1,CTGF蛋白的表达,升高Smad7 mRNA的表达。表明HDN抗肝纤维化作用可能与其调控TGF-β1/Smad信号通路,从而抑制HSC的活化、增殖有关。
Liver fibrosis is a common pathological process for chronic liver injury caused by muhiple etiological factors and an inevi- table phase leading to liver cirrhosis. According to the previous studies, hesperidin （HDN） shows a very good protective effect on CCI4-induced chemical hepatic fibrosis in rats. In this experiment, based on the findings of the previous studies, a platelet-derived growth factor （PDGF）-induced HSC-T6 model was established to observe the inhibitory effect of HDN on HSC-T6 proliferation. The ELISA method was adopted to detect the content of collagen I in HSC-T6 supernatant. Transforming growth factor （ TGF）-β1, Smad2, Smad3, Smad7 and connective tissue growth factor （CTGF） mRNA expressions were measured by RT-PCR; TGF-β1 and CT- GF protein expressions in HSC-T6 were determined by Western blot, in order to study I-IDN＇s effect on TGF-β1 signaling pathway in HSC and its potential action mechanism. The results demonstrated that HDN could notably improve I-ISC-T6 proliferation, Collagen I growth and TGF-β1, Smad2, Smad3 and CTGF mRNA expressions. After being intervened with HDN, it could notably inhibit HSC-T6 proliferation and Collagen I growth, reduce TGF-β1, Smad2, Smad3 and CTGF mRNA and TGF-β1, CTGF protein expressions and increase Smad7 mRNA expression. HDN＇s anti-hepatic fibrosis effect may be related to the inhibition of HSC proliferation and activa- tion by modulating TGF-β1/Smad signaling pathway.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2015年第13期2639-2643,共5页
China Journal of Chinese Materia Medica
