Title:Ursodeoxycholic Acid (UDCA) Reduces Hepatocyte Apoptosis by
Inhibiting Farnesoid X Receptor (FXR) in Hemorrhagic Shock (HS)
Volume: 23
Issue: 6
Author(s): Lu Wang, Xi Rui, Huai-Wu He, Xiang Zhou*Yun Long*
Affiliation:
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking
Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences,
Beijing, China
- Department of Critical Care Medicine, State Key Laboratory of Complex Severe and Rare Diseases, Peking
Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences,
Beijing, China
Keywords:
Ursodeoxycholic acid, hepatocyte apoptosis, farnesoid X receptor, hemorrhagic shock, liver injury, trauma.
Abstract:
Background: Hemorrhagic shock (HS) is the most common cause of
potentially preventable death after traumatic injury. Acute liver injury is an important
manifestation of HS. Apoptosis plays an important role in liver injury. Farnesoid X
receptor (FXR) can alleviate liver injury. This study aimed to examine the effects of
ursodeoxycholic acid (UDCA) on hepatocyte apoptosis in HS and its relationship with
the FXR pathway.
Methods: Mice were randomly divided into 4 groups: sham group, HS group, HS +
UDCA group, and FXR (-) + HS + UDCA group. There were 6 mice in each group. As to
the model of HS, MAP of 40 ± 5 mmHg was maintained for 1 hour. As to UDCA
intervention, UDCA (300mg/kg) was given nasally. Real-time RT-PCR and Western
blotting were used to detect changes in the expression level of Caspase-3, Bax, LC3Ⅰ,
LC3Ⅱ, Bcl-2, and Beclin-1 in the liver. TUNEL assay was used to detect changes in
hepatocyte apoptosis.
Results: The expression level of Caspase-3 and Bax in the liver decreased significantly
after treatment with UDCA under HS conditions. The expression level of LC3Ⅰ, LC3Ⅱ,
Bcl-2, and Beclin-1 in the liver increased significantly after treatment with UDCA under
HS conditions. TUNEL positive percentage of liver decreased significantly after
treatment with UDCA under HS conditions. In the case of FXR (-), the influence of
UDCA was inhibited.
Conclusion: These results indicated that UDCA could reduce hepatocyte apoptosis
during HS through the FXR pathway.
