Dimethyl fumarate alleviates DEHP-induced intrahepatic cholestasis in maternal rats during pregnancy through NF-κB/NLRP3 signaling pathway
10.19405/j.cnki.issn1000-1492.2025.01.016
- Author:
Yue Jiang
1
,
2
,
3
;
Yun Yu
3
,
4
;
Lun Zhang
3
,
4
;
Qianqian Huang
3
,
4
;
Wenkang Tao
1
,
2
,
3
;
Mengzhen Hou
1
,
2
,
3
;
Fang Xie
1
,
2
,
3
;
Xutao Ling
1
,
2
,
3
;
Jianqing Wang
1
,
2
,
3
Author Information
1. Department of Pharmacy，Anhui Medical University，Hefei 230032
2. Dept of Pharmacy， The First Affiliated Hospital of Anhui Medical University，Hefei 230012
3. Dept of Pharmacy， Anhui Public Health Clinical Center，Hefei 230012
4. Dept of Pharmacy， The First Affiliated Hospital of Anhui Medical University，Hefei 230012
- Publication Type:Journal Article
- Keywords:
intrahepatic cholestasis of pregnancy;
dimethyl fumarate;
di (2-ethylhexyl) phthalate;
inflammation;
NF-κB;
NLRP3 inflammasome
- From:
Acta Universitatis Medicinalis Anhui
2025;60(1):117-123
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism.
Methods :Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3.
Results :Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05).
Conclusion :DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.
- Full text:202503051002288035富马酸二甲酯通过NF-κB...导的母鼠妊娠期肝内胆汁淤积_蒋月.pdf
