Effect of High Concentration Estradiol on Acute Autoimmune Hepatitis Induced by ConA
- VernacularTitle:高浓度雌二醇对刀豆蛋白A诱导小鼠急性自身免疫性肝炎的影响
- Author:
Yi-wen ZHANG
1
;
Li WANG
1
;
Su-li QIU
1
;
Qiu-yang LI
1
;
Zhe LI
1
;
Cheng-fang XU
1
Author Information
1. Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, Guangzhou 510630, China
- Publication Type:Journal Article
- Keywords:
estrogen;
ConA;
autoimmune hepatitis
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2021;42(2):185-192
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo study the effect of the high-concentration estrogen (EE) on acute autoimmune hepatitis (AIH) and to explore its possible molecular mechanism. MethodsTwenty 8-week-old female C57BL/6 mice were randomly divided into 4 groups according to body weight,5 in each group. The mice in control(CON)group,ConA-treated(ConA)group,estradiol-treated(EE)group and treatment-combined(EE+ConA)group were treated with EE for two weeks by intraperitoneal injection after ovariectomy. After the last administration for 24 h, the caudal vein was injected with concanavalin A to establish AIH model. H&E, serum ATL, and AST were used to test AIH model. Apoptosis in liver tissues was detected by TUNEL. ELISA was employed to determine the levels of interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in serum. AML2 was treated with EE of different concentrations for 24 h and 48 h respectively. The cell viability was detected by CCK-8 assay and apoptosis was detected by Annexin V-FITC/PI flow cytometry. ResultsH&E and serum revealed that compared with those in Control and ConA, the degree of liver damage was increased significantly in EE+ConA group. The level of serum ALT and AST in EE+ConA group were also increased significantly (P < 0.000 1, P < 0.000 1). TUNEL: The numbers of TUNEL positive cells increased significantly in EE+ConA, (P<0.000 1). ELISA results showed that compared with those in Control and ConA, in EE+ConA, the levels of IL-6 and TNF-α in serum had a significant rise, (P < 0.0001, P=0.024 7). Compared with Control and ConA, high concentration of EE treated AML12 group indicated lower cell viability, P < 0.05. In light of the result of flow cytometry, high concentration of EE could significantly promote hepatocyte apoptosis, (P<0.05). ConclusionHigh concentration of estradiol may promote the secretion of inflammatory cytokines such as TNF-α and IL-6, induce hepatocyte apoptosis, and aggravate the hepatic inflammation in AIH mice.