| Objective: Hepatic fibrosis (HF) is common pathologic process in several chronic liver diseases. Necrosis and the inflammation stimulation in hepatocyte resulting in unbalance of hyperplasia and degradation of extracellular matrix (ECM) induce a deposition of fibrous connective tissue in the liver. At present activation of the hepatic stellate cell (HSC) is still considered as the core of development of liver fibrosis. Heme oxygenase (HO) is a rate-limiting enzyme in the haem metabolic pathway. HO-1, one of HO isozymes, a protective protein, with its catalysate biliverdin, bilirubin and carbon monoxide, play remarkable role in anti-inflammatory, anti-hyperplasia and regulation of cytokine expression. Many evidences show that HO-1 has the protective function in liver transplant, acute hepatic injury and ischemic reperfusion injury. However, the relation between HO-1 and liver fibrosis remains unknown. In this study, we investigated the effect of HO-1 on fibrosis by inducing HO-1 expression with cobalt protoporphyrin (CoPP) in immune liver fibrosis of rats.Methods: Fifty-two male SD rats were divided into three groups: control group 12 (N group), liver fibrosis group 20 (F group) and cobalt protoporphyrin group 20 (Co group). F group was established immune liver fibrosis with the human serum albumin (HSA) attacking. Co group was administrated CoPP intraperitoneally at the same time of HSA attacking. N group was treated with saline. After 6 weeks of attacking, all rats were killed. Expression of HO-1 protein was observed by Western blot analysis and the immunohistochemical method. Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) were assayed using an automatic blood biochemistry analyzer. Contents of hyaluronic acid (HA), laminin (LN), typeâ…¢precollagen (PCâ…¢) and typeâ…£collagen (â…£-C) in blood were assessed by the mean of radioimmunoassay. HE staining was performed to assess fibrosis proliferation and its distribution, proliferation extent of fibroblast, and alterations of hepatocyte and inflammatory cell. Typeâ… andâ…¢collagen were detected by Van Gieson's (VG) staining and Foot staining, respectively. In addition, the spindle-shaped cells which existed at perisinusoid location beyond portal and septa area were investigated by HE staining.Results:1. HO-1 protein expression in F group was significantly higher than in N group (P<0.01), and more increase was observed in the Co group (P<0.05) according to both of Western blot analysis and immunohistochemical method.2. The contents of serum HA, LN, PCâ…¢andâ…£-C were diminished (P<0.01), and proliferation degrees of fibroblast, typeâ… andâ…¢collagen were depressed by CoPP. CoPP reduced liver fibrosis degree.3. CoPP decreased levels of serum ALT and AST (P<0.01), and lighten the injury of hepatocytes.4. CoPP reduced the number of the spindle-shaped cells which existed at perisinusoid location beyond portal and septa area which was increased in F group.5. CoPP decreased significantly less inflammatory cell infiltration around the portal area and the central veins.Conclusion:1. The expression of HO-1 protein increased in liver tissue of immunity liver fibrosis rat. CoPP may induce a much higher expression of increase of HO-1, which may in turn suppress the development of liver fibrosis.2. CoPP inducing an increase of HO-1 may protect the liver during immune liver fibrosis process,3. In the process of immune liver fibrosis, CoPP inducing an increase of HO-1 may suppress the infiltration of the inflammatory cells. 4. CoPP inducing an increase of HO-1 probably suppressed transformation of HSC to fibroblast in the process of immune liver fibrosis.5. Increase of endogenous HO-1 induced may suppress the liver fibrosis by protecting liver cells, suppressing the inflammatory cell infiltration and HSC transformation, which may provide a new method to intervent liver fibrosis with medicine.
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