Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
Biochem Pharmacol. 2010 Dec 1;80(11):1718-26. doi: 10.1016/j.bcp.2010.08.020. Epub 2010 Sep 9.
Liver fibrosis is a consequence of chronic liver disorders which lead to the accumulation of extracellular matrix (ECM). Particularly, there is an increased accumulation of collagen in the fibrotic liver. We have therefore used a triplex forming oligonucleotide (TFO) against the type α1(I) collagen and evaluated, whether it can attenuate liver fibrosis induced by common bile duct ligation (CBDL) in rats. There was a significant decrease in hydroxyproline levels and Masson's trichrome staining for collagen in TFO-treated CBDL groups compared to non-treated CBDL group. There was over expression of type α1(I) collagen, α-smooth muscle actin (α-SMA) and TGF-β1 expression in the CBDL group compared to TFO-treated CBDL group. Also, the serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were less in the TFO treated group compared to non-treated CBDL group. There was also less neutrophils accumulation in TFO treated CBDL group assayed by myeloperoxidase (MPO) assay. These results suggests that TFO can be used to downregulate type 1 collagen gene expression and can alleviate liver fibrosis induced by common bile duct ligation.
肝纤维化是慢性肝脏疾病导致细胞外基质（ECM）积累的结果。特别是，纤维化肝脏中胶原的积累增加。因此，我们使用了一种针对α1(I)型胶原的三链体形成寡核苷酸（TFO），并评估了它是否可以减轻胆总管结扎（CBDL）诱导的大鼠肝纤维化。与未治疗的 CBDL 组相比，TFO 治疗的 CBDL 组羟脯氨酸水平和胶原 Masson 三色染色显著降低。与 TFO 治疗的 CBDL 组相比，CBDL 组中α1(I)型胶原、α-平滑肌肌动蛋白（α-SMA）和 TGF-β1 的表达过度。此外，与未治疗的 CBDL 组相比，TFO 治疗组血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）浓度较低。髓过氧化物酶（MPO）测定也表明，TFO 治疗的 CBDL 组中性粒细胞积聚减少。这些结果表明，TFO 可用于下调 1 型胶原基因表达，并可减轻胆总管结扎引起的肝纤维化。
