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.
Curr Mol Med. 2023;23(6):550-558. doi: 10.2174/1566524022666220525152811.
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.
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.
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.
These results indicated that UDCA could reduce hepatocyte apoptosis during HS through the FXR pathway.
出血性休克（HS）是创伤后潜在可预防死亡的最常见原因。急性肝损伤是 HS 的重要表现。细胞凋亡在肝损伤中起重要作用。法尼醇 X 受体（FXR）可减轻肝损伤。本研究旨在探讨熊去氧胆酸（UDCA）对 HS 肝细胞凋亡的影响及其与 FXR 通路的关系。
将小鼠随机分为 4 组：假手术组、HS 组、HS+UDCA 组和 FXR（-）+HS+UDCA 组，每组 6 只。HS 模型中，维持 MAP 为 40±5mmHg 1 小时。UDCA 干预时，经鼻给予 UDCA（300mg/kg）。采用实时 RT-PCR 和 Western blot 检测肝组织 Caspase-3、Bax、LC3Ⅰ、LC3Ⅱ、Bcl-2 和 Beclin-1 表达水平的变化。TUNEL 检测法检测肝细胞凋亡的变化。
在 HS 条件下，UDCA 处理后肝组织 Caspase-3 和 Bax 的表达水平明显下降。在 HS 条件下，UDCA 处理后肝组织 LC3Ⅰ、LC3Ⅱ、Bcl-2 和 Beclin-1 的表达水平明显升高。在 HS 条件下，UDCA 处理后肝组织 TUNEL 阳性率明显下降。在 FXR（-）的情况下，UDCA 的影响受到抑制。
这些结果表明，UDCA 可通过 FXR 通路减少 HS 时的肝细胞凋亡。
