RESUMO
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, LC3â , LC3â ¡, 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 LC3â , LC3â ¡, 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.
Assuntos
Choque Hemorrágico , Ácido Ursodesoxicólico , Camundongos , Animais , Ácido Ursodesoxicólico/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia , Proteína Beclina-1/metabolismo , Proteína Beclina-1/farmacologia , Fígado/metabolismo , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , HepatócitosAssuntos
Gasometria , Hiperóxia , Aconitato Hidratase , Dióxido de Carbono , Humanos , Consumo de OxigênioRESUMO
OBJECTIVE AND DESIGN: Hepatocytes emerge from a quiescent state into a proliferative state to recover from septic injury. We hypothesize that hepatocyte cell cycle regulation after sepsis potentially contributes to the recovery of liver function. METHODS: An animal model of sepsis was induced by cecal ligation and puncture (CLP) in rats. At serial time points after CLP, hepatocyte expression of p21, P53, cyclin D1, cyclin E, CDK2, CDK4 and PCNA was determined by immunoblot analysis, and the DNA content of isolated hepatocytes was analyzed using flow cytometry. RESULTS: Sepsis-induced liver injury of rats was associated with G1 cell cycle arrest. Recovery of liver function was related to cell cycle progression 48 h after CLP. The upregulation of p53 and p21 correlated with G1 cell arrest 48 h after CLP. The upregulation of cyclin D1/CDK4 and cyclin E/CDK2 also correlated with the G1/S transition 48 h after CLP, resulting in PCNA expression. CONCLUSIONS: The data suggests that G1 cell cycle arrest and p53, p21, CDKs, cyclins and PCNA expression may be involved in the injury/recovery of liver function after intraperitoneal sepsis.