| 研究実績の概要 |
Mice were sacrificed at 1-3 weeks after BDL, 10 weeks after thioacetamide (TAA) injection, 8-32 weeks after CDAA feeding or 12 months after diethylnitrosamine (DEN) treatment. In BDL model, compared to WT, fibrosis was robustly developed in KO mice indicated by markedly increased expression of α-SMA, collagen 1a1, and Sirius-red positive area. TG mice showed suppression of these factors up to 55% compared to WT mice. Similary results were also found in TAA, CDAA, and DEN model. Specially, in DEN model, 100% liver-, and 40% lung-tumours were found in KO mice, but only 40% and 0%, respectively, in WT mice. In contrast, TG mice showed significantly regressed the mean number (4.76 vs 1.51, p<0.001), and maximum size (7.4 vs 2.05 mm, p<0.01) of liver tumours compared to WT ones.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
In vivo administration of rhCYGB exhibited no toxicity to mouse organs and their livers. Tail vein-injected Alexa 488-labelled rhCYGB accumulated in multiple organs, of note, in the liver, it was localized in HSCs and sinusoidal endothelial cells, but not in hepatocytes. In vivo mouse liver fibrosis model induced by ten weeks injection of escalation dose of TAA developed severe liver injury, inflammation, oxidative stress and fibrosis, while all of these manifestations were reversed by rhCYGB (2 mg/kg BW, twice/week) treatment during the last 2 weeks or 5 weeks of TAA administration. rhCYGB administration suppressed up to 60% of AST, ALT, 47% of LDH serum levels, 78% of α-SMA, 72% of Col1a1, 43% of Tgf-β1, 53% of Tgf-β3, 79% of Timp-1, 52% of 4-HNE, 44% of HO-1 expression induced by TAA.
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