Objective This study is to explore the role of 78 kD glucose-regulated protein (GRP78) in development of hepatopulmonary syndrome (HPS) in rats. of ALT and TNF-α in plasma and the contents of TNF-α and MDA in lung tissues were gradually increased along with the disease progression with a strong positive correlation. Compared with controls the plasma TNF-α level and the mRNA and protein expression levels of GRP78 in lung tissues were significantly higher in rats with HPS. The levels of endotoxin and ALT in plasma and the level of MDA in lungs were significantly higher in rats with HPS than controls. Conclusions The increased GRP78 expression is indicative of endoplasmic reticulum stress response during HPS which may play an important bcl-xS role in the disease pathogenesis. values of less than 0.05 were considered statistically significant. Results Biochemical indexes in plasma and lung tissues in HPS models To characterize the biochemical indexes of HPS models the levels of endotoxin TNF-α ALT and MDA in the plasma and lung tissues were investigated. As EMD-1214063 indicated in Table 1 and Table 2 the level of endotoxin in plasma was increased as the disease progressed in HPS groups with significant differences between these groups (< 0.05). The levels of TNF-α in plasma and lung tissues and the level of MDA in plasma were also increased with the progression of the disease in HPS groups with significant differences between groups (< 0.05). All the biochemical indexes in the 6-wk and 8-wk HPS groups were significantly increased from that in corresponding control groups (< 0.05). Table 1 Levels of endotoxin TNF-α and ALT in the plasma in control and HPS groups. Table 2 Levels of TNF-α and MDA in the lung tissue in control and HPS groups. Pathological changes in liver and EMD-1214063 lung tissues in HPS models To determine the pathological features of HPS models H&E staining was performed both in liver and lung tissues in control and HPS groups. As shown in Fig. 1 HE staining indicated regular lobular structures and intact radial hepatic cord arrangement around the central vein and the hepatic cells were rich in cytoplasm and revealed blue round nuclei in the control EMD-1214063 group (Fig. 1A). In the livers in 4-wl HPS group the arrangement of hepatic cords was irregular and the necrosis of central hepatic lobule was detected accompanied by inflammatory cell infiltration. Steatosis was found in some hepatocytes and the interlobular fibroplasias was also observed (Fig. 1B). As shown in Fig. 1C the hepatic steatosis and the inflammatory cell infiltration were aggravated and the proliferating fibrous network took place in the 6-wk HPS group. Furthermore pseudolobule was formed in the 8-wk HPS group (Fig. 1D). Figure 1 Pathological changes in liver and lung tissues in HPS models (H & E staining × 100). (A) Normal liver EMD-1214063 tissue in control group. (B) Liver cirrhosis in 4-wk HPS group. (C) Liver cirrhosis in 6-wk HPS group. (D) Liver cirrhosis in 8-wk HPS … For the lung tissues H&E staining revealed that the alveolar structure was intact with uniform septum in control group (Fig. 1E). In 4-wk HPS group the alveolar septal walls were slightly thickened and the accumulation of macrophages and neutrophils was observed (Fig. 1F). When induced for 6 wk the alveolar septal walls were moderately thickened accompanied by telangiectasis and accumulated EMD-1214063 macrophages and neutrophils and some of the alveolar cavities became smaller (Fig. 1G). The alveolar septal walls were further thickened and the alveolar cavities became even smaller and capillaries with increased lumen and plenty of accumulated macrophages were found EMD-1214063 in alveolar septal walls in 8-wk HPS group (Fig. 1H). Elevated protein and mRNA expression levels of GRP78 in lung tissues in HPS models To investigate the role of GRP78 in HPS pathogenesis its protein and mRNA expression levels in lung tissues were detected. The results indicated GRP78 expression was elevated as the disease progressed at both protein (Fig. 2) and mRNA (Fig. 3) levels with significant differences between HPS groups (< 0.05). At each time point the protein and mRNA expression levels of GRP78 are both significantly higher than matching handles (< 0.05) (Fig. 2B and ?and3B).3B). These outcomes claim that the proteins and mRNA appearance degrees of GRP78 are elevated in lung tissue from the HPS versions. Amount 2 The proteins expression degrees of GRP78 in lung tissue in HPS versions. (A) The proteins degree of GRP78 in lungs was.