Abstract
Objective To investigate the reversal effect of allografted hepatocyte transplantation (HTx) on the progress of liver fibrosis in rats and to study the mechanism. Methods HTx were performed on the rats with liver fibrosis that were induced by CCl4 injection intraperitoneally for 21 days.Liver fibrosis rats not receiving hepatocytes transplantation and normal rats receiving hepatocytes transplantation were studied simultaneously as control group. Plasma and liver tissue samples were collected at 1st, 2nd, 7th and 14th day after HTx. Total and active TGF-β1, plasmin and α2M in plasma were analyzed by ELISA. Imaging and quantitation of collagen, activation of hepatic stellate cells within liver tissue were also studied by computer assistant imaging analysis. Results Two weeks after ceasing of CCl4 injection, the liver fibrotic area in the rats undergoing HTx was significantly less than that in the spontaneous recovery group (3. 69 % ± 0. 44 % vs. 8. 25 % ± 0. 69 %, P＜0. 01). The positive signal area of α-SMA in the experimental group was also less than that in the control group (0. 43 % ± 0. 03 % vs. 2. 79 % ± 0. 40 %, P＜0. 01 ). One day after HTx, the total TGF-β1 level was decreased from (4543. 2 ± 307. 2) to (2109. 9 ± 425. 2) μg/ml, while the level of active TGF-β1 was also decreased from (2380. 7 ± 150. 8) to (1758. 9 ± 429. 2) μg/ml. The concentration of plasmin in plasma was decreased significantly from (5. 16±0. 42) to (2. 96±0. 11) μg/ml after HTx. In the experimental group the concentration of α2M was increased more than two times after HTx, from (152. 4 ± 27. 6) to (343. 0 ± 48. 8) mg/ml, while in normal rats undergoing HTx, α2M was increased almost thirty times. Conclusion HTx can benefit the reversal of liver fibrosis in rats. The inactivation of HSCs and the internalization of TGF-β1 by hepatocytes may ultimately responsible for this event. Key words: Cell transplantation; Hepatocytes; Fibrosis; Transforming growth factor-beta; Rats
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