Phosphonate inhibits steatosis and lobular inflammation of non-alcoholic steatohepatitis through depleting macrophages
10.3760/cma.j.cn501113-20191024-00394
- VernacularTitle:膦酸盐通过消耗巨噬细胞抑制非酒精性脂肪性肝炎的脂肪变和小叶炎症
- Author:
Lingling SHI
1
;
Zhaolian BIAN
;
Dengfu YAO
;
Min YAO
;
Jianguo SHAO
Author Information
1. 南通大学附属南通第三人民医院消化内科 226001
- Keywords:
Fatty liver;
Macrophage;
Clodronate liposomes;
Methionine and choline deficient
- From:
Chinese Journal of Hepatology
2021;29(3):253-258
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the role of macrophages in non-alcoholic steatohepatitis (NASH) in order to provide directions for the therapeutic target of metabolic liver disease.Methods:Twenty C57BL/6 wild-type male mice at 6-8 weeks were randomly divided into two groups: 5 in the control group, methionine-and choline-deficient diet (MCD); 15 in the experimental group, MCD diet + intraperitoneal injection of disodium chlorophosphonate liposomes (to clear macrophages). Mice were fed for 4 weeks to establish NASH model. Blood, liver and spleen were collected to analyze the body mass index, liver index, spleen index, and serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Non-alcoholic steatosis (NAS) activity score was evaluated by HE and Oil Red O staining. The relative expression level of F4/80 mRNA was compared by RT-PCR. Data comparison between groups was analyzed by t-test.Results:NASH model was successfully established by feeding the mice with MCD for four week. The expression of F4/80 mRNA ( t = 4.167, P < 0.01), hepatic steatosis ( t = 10.70, P < 0.05), interlobular inflammatory infiltration ( t = 3.08, P < 0.05), and NAS score were decreased ( t = 8.06, P < 0.05) in the experimental group. At the same time, ALT level [(817.00 ± 128.90) U/L vs. (231.20 ± 36.28) U/L, t = 5.71, P < 0.01], AST level [(1 211.00 ± 248.90) U/L vs. (505.30 ± 88.20) U/L, t = 3.32, P < 0.01] was decreased significantly. However, the spleen volume and spleen index of the experimental group were larger (0.24 ± 0.01 and 0.32 ± 0.02, t = 2.41, P < 0.05), and there was no significant effect on liver ballooning, body mass index and liver index. Conclusion:In NASH, phosphonate can consume macrophages to inhibit liver inflammation and protect the damaged liver.
