Effect of umbilical cord mesenchymal stem cells on acute liver injury induced by endotoxemia in rats

Abstract

Objective To evaluate the effect of umbilical cord mesenchymal stem cells(hUC-MSCs) on acute liver injury induced by endotoxemia in rats and its relationship with the mechanism of apoptosis. Methods 18 male SD rats were randomly divided into a control group (Group C), an endotoxemia group (Group M) and an endotoxemia with the treatment of hUC-MSCs group (Group M+cells). A rat model of endotoxemia was established by intraperitoneal injection of lipopolysaccharide (LPS, 5mg/kg). 20×106 hUC-MSCs was infused into the mice of Group M+cells through the tail vein. Four hours later, the serum AST, ALT, TNF-α and IL-6 were measured. The expression of JUN amino-terminal kinase (JNK), apoptosis signal regulated kinase 1 (ASK1), Bcl-2 protein and Bax in the liver tissues was detected by Western Blot method. HE staining was used in histopathology, and then the liver histopathology was observed under a light microscope. Results (1) Compared with Group C, the concentration of AST, ALT, TNF-α and IL-6 in Group M and M+cells was higher than that in Group C (P < 0 05). Compared with Group M, the concentration of AST, ALT, TNF-α and IL-6 in Group M+cells was lower than that in Group M (P < 0.05). (2) The morphology of hepatocytes in Group C was normal and the structure of hepatic lobule was clear. There was no inflammatory cell infiltration in portal area of the liver. While, the scattered nodular necrosis of hepatocytes associated with inflammation could be seen in the hepatic lobules of rats in Group M. Less inflammatory cells infiltration in the hepatic lobules and infiltration of Kuffer cells were found in hepatocyte space in Group M+cells. (3) Compared with Group C, the expression of JUN, ASK1 and Bax protein in the liver tissues of Group M was significantly higher than that of Group C (P < 0.05), while the expression of Bcl-2 protein was decreased (P < 0.05). Compared with Group M, the expression of JUN, ASK1 and Bax protein in the liver tissues of Group M+cells was lower than that of Group M (P < 0.05), while the expression of Bcl-2 protein was significantly increased (P < 0.05). (4) Single factor analysis showed that serum ALT, AST were positively correlated with TNF-α index (r value were 0.9580, 0.9865, P < 0.05), and serum ALT, AST were positively correlated with IL-6 index (r value were 0.9892, 0.9630, P < 0.05). The serum ALT, AST were positively correlated with BAX, ASK1, JNK index(r value were 0.9993, 0.9851, 0.7901, 0.9864, 0.9557, 0.7128, all P < 0.05). Serum ALT and AST were negatively correlated with Bcl-2 index (r = -0.8824, -0.9338, all P < 0.05), serum TNF-α was positively correlated with Bax, ASK1, JNK index (r = 0.9466, 0.8958, 0.6025, all P < 0.05), and serum TNF-α was negatively correlated with Bcl-2 index (r = -0.6025, all P < 0.05). Serum IL-6 was positively correlated with Bax, ASK1 and JNK indexes (r values were 0.9941, 0.9997 and 0.8679, all P < 0.05), while serum IL-6 was negatively correlated with Bcl-2 index (r = -0.8078, P < 0.05). Key words: Endotoxemia; Liver injury; Umbilical cord mesenchymal stem cells