Expression of 78 kD glucose-regulated protein is increased in cirrhotic cardiomyopathy induced by intestinal endotoxin

Aims: This study is to investigate the role of 78 kD glucose-regulated protein (GRP78) in cardiomyopathy induced by intestinal endotoxin in a rat model of liver cirrhosis. Methods: The liver cirrhosis model was established by challenging rats with carbon tetrachloride, lard and alcohol. A total of 51 male SD rats were randomly divided into liver cirrhosis group (n = 33) and control group (n = 18). Measurements were conducted at week 4, week 6 and week 8 of the liver cirrhosis modeling. At each time point, 11 rats of the liver cirrhosis group and 6 rats of the control group were used. The cardiac functions were determined at week 8. Levels of tumor necrosis factor-α (TNF-α) and malondialdehyde (MDA) were detected by radioimmunoassay and thiobarbituric acid assay, respectively. The numbers of cardiomyocytes were detected by toluidine blue staining. The contents of collagen were determined by Van Giesan staining. Expression of GRP78 and hypoxia-inducible factor-1α (HIF-1α) was detected by immnunohistochemistry. Results: The systolic and diastolic function of the heart was significantly decreased in the liver cirrhosis group at week 8 compared with that of the control group (P < 0.05). The levels of TNF-α, MDA, collagen, GRP78, and HIF-1α expression in myocardial tissues were significantly increased in the liver cirrhosis group compared with those in the control group (P < 0.05). The numbers of cardiomyocytes were decreased in the progression of liver cirrhosis (P < 0.05). The plasma endotoxin levels were positively correlated with MDA and GRP78 expression levels in myocardial tissues (P < 0.05). The expression levels of GRP78 were positively correlated with levels of homocysteine, alanine aminotransferase, MDA, and HIF-1α expression (P < 0.05). Conclusion: Expression of 78 kD glucose-regulated protein is increased during myocardial remodeling induced by intestinal endotoxin in the rat model of liver cirrhosis.