Authors

Miao Zhao1, #, Haotao Zeng2, #, *, Zhanxiang Zhang3, Zenglin Liu4, Yuhuang Yang1, Limei Luo1


Departments

1Department of Clinical Laboratory, E.N.T Hospital, Shenzhen, PR China - 2Department of Pharmacy, E.N.T Hospital, Shenzhen, PR China - 3Department of Pharmacology, Shenzhen Luohu People’s Hospital, Shenzhen, PR China - 4Shenzhen Longgang District Maternity & Child Healthcare Hospital, Shenzhen, PR China

Abstract

Objective: To analyze 1,25(OH)2D3 regulation of the activation and proliferation of rat HSCs by regulating the immune microenvironment mediated by IL-17. 

Methods: Forty SD rats were randomly divided into normal (10 rats), model (10 rats), drug control (10 rats) and treatment (10 rats) groups. Rats in each group except the normal group were injected with 40% carbon tetrachloride (peanut oil solution was used as menstruum) subcutaneously to establish liver fibrosis models, and the rats in the treatment group were orally administered with 1,25(OH)2D3 solution (peanut oil solution was used as menstruum) from the day of modelling, and the drug control group was administered with an equal amount of peanut oil vehicle orally, 1 d/time. Four items of liver fibrosis, serum 25(OH)D3 concentration and IL-17 level were detected in each group; HE staining was used to observe the pathological changes of liver tissue in each group of rats; A Western blot method and real-time quantitative PCR were used to detect the expression of IL-17, MIP3α, RORγt protein and mRNA in liver tissue of rats in the groups, respectively. 

Results: The four fibrosis indicators of rats in both model and drug control groups were significantly higher than those in the normal group (P<0.05), and the indicators in the treatment group were significantly lower than those in the drug control group (P<0.05); The concentration of 25(OH)D3 in both control and drug control groups was significantly lower than that in the normal group, and the level of IL-17 was significantly higher than that in the normal group (P<0.05). The concentration of 25(OH)D3 in the treatment group was significantly higher than that in the drug control group. The level of IL-17 was significantly lower than that of the drug control group (P<0.05). The pathological changes of liver tissue in each group showed that the degree of inflammation and fibrosis of liver cells was significantly reduced in the treatment group compared with the drug control group. The expressions of IL-17, MIP3α, RORγt, mRNA and protein in liver tissue of rats in model group and drug control group were significantly higher than those in the normal group, and the difference was statistically significant (P<0.05). Those expressions in the treatment were significantly lower than those of the drug control group, and the differences were statistically significant (P<0.05). 

Conclusion: 1,25(OH)2D3 has a significant inhibitory effect on the formation of rat liver fibrosis and can significantly reduce the expression of IL-17 and its related factor proteins and genes in rat liver tissue, suggesting that 1,25(OH)2D3 may regulate the activation and proliferation of rat HSC and prevent the development of fibrosis by regulating the IL-17-mediated immune microenvironment. 

Keywords

1,25(OH)2D3, IL-17, immune microenvironment, HSC, activation, proliferation.

DOI:

10.19193/0393-6384_2021_2_197