标题: AASLD 2011: Vitamin D has a protective antifibrotic effect in rat model of liver [打印本页] 作者: StephenW 时间: 2011-10-25 23:03 标题: AASLD 2011: Vitamin D has a protective antifibrotic effect in rat model of liver
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Vitamin D has a protective antifibrotic effect in rat model of liver fibrosis
S. Reif1, 2; A. Bentov1, 2; E. Sharvit1, 2; E. Brazowski3; Y. Weisman1; S. Abramovitch1, 2
1. Department of Pediatrics, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
2. Pediatric Gastroenterology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
3. Pathology, Tel-Aviv Sourasky Medical Center, Tel Aviv, Israel.
Background and Aim: In our previous In vitro study, we showed that HSCs proliferation induced by PDGF was suppressed by vitamin D. In addition, collagen I?1 promoter activity, mRNA and protein expression levels were all down-regulated after treatment with vitamin D. Furthermore, exposure to vitamin D led to up-regulation of MMP-9 activity and suppression of TIMP1 mRNA levels. Therefore, in the present study, we investigate the potential of vitamin D treatment to prevent development of liver fibrosis in in vivo model.
Methods: Rats were divided into four groups: no treatment (control), TAA treatment, vitamin D treatment and TAA with vitamin D treatment. Liver fibrosis was induced in rats by administration of thioacetamid (TAA) (200mg/Kg, i.p., twice weekly) for 10 weeks. Treatment with vitamin D (5?g/Kg i.p., twice weekly) was simultaneously given with TAA. Hepatic fibrosis scores were determinate after staining with hematoxylin & eosin and sirius-red. Collagen I deposition was determent following sirius-red staining. ?SMA expression was detected by western blotting
Results: Macroscopically, TAA treated group developed cirrhosis. However, rats received TAA with vitamin D treatment, showed almost normal morphology. Microscopically, the hepatic fibrosis score of the TAA treatment group was 3.9 + 0.1, while rats treated with TAA and vitamin D demonstrated only mild fibrosis and scored of 2.3 + 0.3 (P<0.05). No fibrosis was observed in the control rats or the group received vitamin D alone. Quantification of collagen content, following sirius-red staining demonstrated increased collagen deposition in rats treated with TAA by 16-fold compared to the untreated group. However, administration of TAA with vitamin D significantly decreased collagen levels by 4-fold compared to the TAA group. TAA treatment increased ?SMA expression to ~160%, while addition of vitamin D suppressed ?SMA expression to the control level. Neither hypercalcemia nor renal toxicity was found in rats receiving vitamin D treatment.
Conclusions: These results suggest that treatment of vitamin D can inhibit the development of cirrhosis in a rat model. Hence, vitamin D may play an important role in preventive treatment for liver fibrosis, and may have a potential therapy.
维生素D在大鼠肝纤维化模型的保护抗肝纤维化作用
S.赖夫1，2; A. Bentov 1，2; E. Sharvit 1，2; E. Brazowski 3; Y.韦斯曼1，S.阿布拉莫维奇1，2
1。儿科，特拉维夫Sourasky医学中心，特拉维夫，以色列。
2。小儿消化科，特拉维夫，以色列特拉维夫Sourasky医学中心。
3。病理学，特拉维夫Sourasky医学中心，以色列特拉维夫。