TGF-β1 反义寡核苷酸对 CCl(4)诱导肝纤维化的影响。

Effects of TGF-beta1 Ribbon Antisense on CCl(4)-induced Liver Fibrosis.

机构信息

Department of Physiology, College of Medicine, Dongguk University, Gyeongju 780-714, Korea.

出版信息

Korean J Physiol Pharmacol. 2008 Feb;12(1):1-6. doi: 10.4196/kjpp.2008.12.1.1. Epub 2008 Feb 28.

DOI:10.4196/kjpp.2008.12.1.1

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2817527/

Abstract

Ribbon-type antisense oligonucleotide to TGF-beta1 (TGF-beta1 RiAS) was designed and tested to prevent or resolve the fibrotic changes induced by CCl4 injection. When Hepa1c1c7 cells were transfected with TGF-beta1 RiAS, the level of TGF-beta1 mRNA was effectively reduced. TGF-beta1 RiAS, mismatched RiAS, and normal saline were each injected to mice via tail veins. When examined for the biochemical effects on the liver, TGF-beta1 mRNA levels were significantly reduced only in the TGF-beta1 RiAS-treated group. The results of immunohistochemical studies showed that TGF-beta1 RiAS prevented the accumulation of collagen and alpha-smooth muscle actin, but could not resolve established fibrosis. These results indicate that ribbon antisense to TGF-beta1 with efficient uptake can effectively prevent fibrosis of the liver.

摘要

为了预防或逆转 CCl4 注射引起的肝纤维化，设计并测试了一种针对 TGF-β1 的带状反义寡核苷酸（TGF-β1 RiAS）。当 Hepa1c1c7 细胞转染 TGF-β1 RiAS 时，TGF-β1 mRNA 的水平被有效降低。TGF-β1 RiAS、错配的 RiAS 和生理盐水分别通过尾静脉注射到小鼠体内。在检测对肝脏的生化作用时，只有 TGF-β1 RiAS 处理组的 TGF-β1 mRNA 水平显著降低。免疫组化研究结果表明，TGF-β1 RiAS 可防止胶原和α-平滑肌肌动蛋白的堆积，但不能逆转已形成的纤维化。这些结果表明，具有高效摄取能力的 TGF-β1 带状反义寡核苷酸可有效预防肝纤维化。

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