Protective effect of vitamin D in mice with acute liver failure
10.3760/cma.j.cn501113-20200701-00360
- VernacularTitle:维生素D对急性肝衰竭小鼠肝脏的保护作用
- Author:
Lisha PAN
1
;
Meiyun HUA
;
Siya XU
;
YuanPing HAN
;
Dongxia LUO
;
Yilan ZENG
Author Information
1. 四川大学生命科学学院，成都 610065
- Keywords:
Vitamin D;
Acute liver failure;
Inflammation
- From:
Chinese Journal of Hepatology
2021;29(6):545-550
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the protective effect of vitamin D in acute liver failure through a mouse model.Methods:Acute liver failure was induced by combining D-galactosamine (D-GalN) lipopolysaccharide (LPS) to observe the effect of long-term vitamin D deficiency on liver injury and inflammatory signals in a mouse model. Acute liver failure was induced by thioacetamide (TAA) to observe the effect of vitamin D deficiency on the survival rate, and further high-dose of vitamin D supplementation protective effect was determined in a mouse model. Liver function was evaluated by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver inflammation by hematoxylin-eosin staining. The expressions of tumor necrosis factor (TNF-α), interleukin (IL) -1β, NOD-like receptor family, pyrin domain containing 3 (NLRP-3), chemokines (CCL2, CXCL1 and CXCL2), etc. in liver tissues were detected by RT-qPCR. The quantitation of macrophages in liver tissue was detected by immunohistochemistry. The comparison between groups were performed by t-test. The survival curve was analyzed by log-rank (Mantel-Cox) test.Results:Long-term vitamin D deficiency had increased acute liver failure sensitivity in mice, which was manifested by increased blood cell extravasation, massive necrosis of parenchymal cells, up-regulation of TNF-α, IL-1β, and NLRP-3 mRNA expression ( P < 0.05), and increased macrophages quantitation ( P < 0.05) in liver tissues. At the same time, vitamin D deficiency had increased the mice mortality rate because of liver injury ( P < 0.01). On the contrary, pre-administration of high dose of vitamin D (100 IU/g) had significantly reduced liver injury, inhibited ALT and AST rise ( P < 0.01), alleviated liver necrosis, and down-regulated the mRNA expression of inflammatory factors in liver tissues ( P < 0.05). Conclusion:Mouse model shows that long-term vitamin D deficiency can aggravate drug-induced acute liver failure and reduce survival rates. Furthermore, high-dose of vitamin D has a certain hepatoprotective effect, which can significantly improve liver necrosis condition and inhibit inflammation. Therefore, adequate vitamin D can retain liver physiological balance to resist liver injury.
