Study on p-p38 expression and its significance in liver tissues of mice with acute liver failure and patients with HBV-related acute-on-chronic liver failure

• Main Author: CHEN Jing
• Format: Article
• Language: zho
• Published: Editorial Department of Journal of Clinical Hepatology 2015-04-01
• Series: Linchuang Gandanbing Zazhi
• Subjects: hepatitis B virvs; liver failure; p38 mitogen-activated protein kinases; disease models; animal
• ISSN: 1001-5256; 1001-5256

ObjectiveTo investigate the expression and significance of phosphorylated p38mitogen-activated protein kinase (p-p38MAPK) in mice with acute liver failure induced by D-galactosamine (D-GalN)/lipopolysaccharide (LPS) and patients with HBV-related acute-on-chronic liver failure (HBV-ACLF). MethodsC57BL/6 mice induced by D-GalN/LPS were used to establish an acute liver failure model, and experimental groups were set up at 0, 0.5, 1, 2, 4, 6, and 8 hours (n=4 for each group). All mice were sacrificed and the samples of liver tissues were given HE staining to observe pathological changes. Western blotting and immunohistochemical staining were used to perform semiquantitative analysis and detect the expression of p-p38MAPK in liver tissues. Meanwhile, the expression of p-p38MAPK in patients with HBV-ACLF, hepatitis B cirrhosis, and chronic hepatitis B was also observed. Independent-samples t test was used to draw comparison between groups. ResultsWestern blotting showed that the expression of p-p38MAPK in liver tissue homogenate increased with time. The semiquantitative analysis showed that the expression was significantly higher in the 6 h group than in the control group (t=-2727,P=0.034). Immunohistochemical staining showed that liver inflammation aggravated with the survival time, and p-p38MAPK was expressed by sinus cells at early stage, and then by liver cells with the damage continued in mice, and there were lots of p-p38MAPK-positive liver cells around the necrotic liver tissues. Expression of p-p38MAPK was very low in normal human liver tissues; however, tumor-infiltrating lymphocytes and p-p38MAPK-positive liver cells could be seen in liver tissues of patients with chronic hepatitis B. Theexpression of p-p38MAPK was increasingly observed with the course of the disease, which was consistent with the aggravation of the disease. ConclusionThe expression of p-p38MAPK is found positively correlated with the liver tissue damage in the mouse model of acute liver failure induced by D-GalN/LPS, implying that p-p38MAPK plays a significant role in the development of acute hepatic failure. In HBV-ACLF patients, the p-p38MAPK signaling pathway may play a critical role in the development of liver failure.