Role of GRP78 in alteration of myocardium induced by intestinal endotoxemia in cirrhotic rats

AIM: To explore the role of glucose-regulated protein 78(GRP78) in the alteration of myocardium induced by intestinal endotoxemia in cirrhotic rats. METHODS: Fifty-one male Wistar rats were randomly divided into liver cirrhosis groups of 4-week,6-week and 8-week,and normal control groups at corresponding time points.The cardiac functions of the 8-week rats were measured.Tumor necrosis factor α(TNF-α) and malondialdehyde(MDA) in myocardial tissues were detected.The number of myocardial cells and the collagen volume fraction(CVF) were determined with toluidine blue and van Giesan staining,respectively.The expression of GRP78 and hypoxia-inducible facotr 1α(HIF-1α) was analyzed by the method of immnunohistochemistry. RESULTS: Compared with normal control group at corresponding time point,left ventricular end-diastolic pressure(LVEDP) and ±LV dp/dtmax in 8-week group were significantly decreased(P0.05).The levels of TNF-α,MDA and CVF,the protein expression of GRP78 and HIF-1α in the myocardial tissues were significantly increased in every model group(P0.05),and the number of myocardial cells was gradually decreased(P0.05).Elevated levels of endotoxin in plasma were positively correlated with the levels of alanine aminotransferase(ALT),homocysteine(Hcy) and TNF-α in plasma,the levels of TNF-α,MDA and CVF,and protein levels of GRP78 and HIF-1α in the myocardial tissues(P0.05).Elevated protein expression of GRP78 in the myocardial tissues was positively correlated with the levels of ALT,Hcy in plasma and MDA,CVF,HIF-1α protein in the myocardial tissues(P0.05). CONCLUSION: Intestinal endotoxemia induced by liver cirrhosis may directly or indirectly lead to endoplasmic reticulum stress and overexpression of GRP78.GRP78 may be a key molecule in the pathogenesis of myocardial remodeling and functional alteration induced by liver cirrhosis.