Abstract
Objective: To observe the therapeutic effects and related mechanism of hemin on the progression of hepatic fibrosis in rats. Methods: Sixty male Wistar rats were randomly divided into normal control group, 4-week model group, 6-week model group, hemin inhibitor zinc protoporphyrin-IX (ZnPP-IX) intervention group and hemin intervention group. Hemin intervention group in complex liver fibrosis model was intraperitonealy administered ZnPP-IX or hemin every other day for 2 weeks from the fourth week. The mRNA expression of HO-1, α-smooth muscle actin (α-SMA) and nuclear factor-κB (NF-κB) in the liver tissue was detected by real-time polymerase chain reaction. Immunohistochemistry was used to detect HO-1 and localization of α-SMA expression. Serum hyaluronic acid, propeptide of type III collagen and hepatic transforming growth factor beta (TGFβ), and interleukin 6 (IL-6) expressions were detected by enzyme-linked immunosorbent assay. The content of hydroxyproline in hepatic tissues was measured by alkaline hydrolysis method. One-way ANOVA was used to compare the mean of each group. The difference between the two groups was compared by independent samples t- test. P-values < 0.05 was considered statistically significant. Results: Compared with model groups and ZnPP-IX intervention group, Hemin's intervention significantly increased the expression of HO-1 mRNA (P < 0.01) and protein distribution in liver tissues, while the expression of alpha-SMA mRNA was significantly decreased (P < 0.05) in portal space and areas around the fibrotic septum, and hepatic sinus. Hyp content and serum hyaluronic acid and propeptide of type III collagen decreased significantly (P < 0.05). Meanwhile, NF-κB p65 mRNA expression and the downstream production of TGFβ and IL-6 in Hemin intervention group were also inhibited (P < 0.05). Conclusion: Hemin can significantly inhibit the progression of hepatic fibrosis in rats by up-regulating HO-1 expression, and the inhibiting activity of NF-κB p65 leads to downstream of the inflammatory factors.