Effect of immune macrophage on liver fibrosis of thioacetamide induced

• Main Authors: Chia-Yi Wang, 王佳怡
• Other Authors: Ching-Feng Weng
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/35sf5y

碩士 === 國立東華大學 === 生物技術研究所 === 95 === Thioacetamide (TAA), a thio-sulfur-containing compound, which is a common inducer for the studying liver fibrosis and cirrhosis. Immune cells are involved in mediation of fibrosis including hepatic macrophages (Kupffer cells), natural killer (NK) cells, and lymphocytes such as T helper (Th) cells and cytotoxic T (Tc) cells. The activated macrophages produce pro-inflammatory mediators that further result in the activation of non-specific immunity. The mediators including superoxide anion, reactive nitrogen intermediates (ROI) and cytokines such as transforming growth factor-β (TGF-β), tumor necrosis factor α (TNF-α), and platelet-derived growth factor are released by the activated macrophages, leading to the development of myofibroblasts (hepatic satllete cells) responsible for the production of extra-cellular matrices (ECMs) and further damaged liver. However, the regulating mechanisms of immunity during live fibrosis are still not clear. In this work, rats were intraperitoneally injected with thioacetamide (TAA, 200 mg/kg Bwt) per 3 days for 1, 5, 10, 15 and 20 times to test the appearance of immune cell populations, phagocytosis, respiratory burst, apoptosis, TNF-α and TGF-β from various tissues including liver, blood and spleen using flow cytometry. The productions of nitric oxide and proliferation of macrophages were determined using an automated microtitre plate spectrophotometer. The results showed that the live fibrosis caused the significant decrease of lymphocytes (CD3+) numbers in blood and the elevation of TGF-β levels secrete by the activated macrophages (OX6+) in spleen. The early stage of liver fibrosis, the numbers of macrophages (Kupffer cells), natural killer (NK) cells, and T helper (Th) cells in liver were suppressed, which increased gradually with the severity of liver fibrosis. Moreover, the increasing numbers of activated macrophage secreted a great of cytokines including TGF-β1 and TNF-α in liver fibrosis. Additionally, rats were intraperitoneally injected with TAA ( 200 mg/kg Bwt) per 3 days for 5 and 15 times and injected again with GdCl3 (10 mg/kg B.wt) 24 h prior to scarified to examine whether the inhibiting effects of liver fibrosis on the phagocytic activity of kupffer cells in livers. The results presented that the liver fibrosis inhibited the phagocytic activity of kupffer cells that had lower efficiency in clearance of the necrotic and apoptotic cells, and enhanced the increase of lymphocytes numbers in liver. Furthermore, the proliferating macrophage induced the increase of the respiratory burst activity resulted in liver serious fibrosis. Liver fibrosis also caused the decrease of phagocytic actvitity in blood and spleen. This result suggests that liver fibrosis leads to the decreases of immunity and inhibits the resistance of pathogen in rat.