Differential regulation of protein S expression in hepatocytes and sinusoidal endothelial cells in rats with cirrhosis
Differential regulation of protein S expression in hepatocytes and sinusoidal endothelial cells in rats with cirrhosis
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DOI：
10.1111/j.1538-7836.2006.02227.x
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发表时间：
2006-12-01
影响因子：
10.4
通讯作者：
Suzuki, K.
中科院分区：
文献类型：
--
作者：
Fujii, K.;Kishiwada, M.;Suzuki, K.
背景：肝硬变患者术后常可观察到鼻窦内微血栓所致的肝功能障碍，但其机制尚不清楚。目的：探讨二甲基亚硝胺诱导的肝硬变大鼠肝切除前后肝细胞和肝窦内皮细胞中S蛋白(PS)的表达。结果：与空白对照组相比，肝硬变大鼠血浆PS抗原水平明显降低。与对照组相比，肝硬变大鼠分离的肝细胞PS表达显著降低。相反，与对照组相比，肝硬变大鼠分离的SECs中PS的表达显著增加。IL-6可上调肝硬变大鼠肝细胞PS的表达，而肿瘤坏死因子-α(TNF-α)可降低其在SECs中的表达。与对照组相比，肝硬变大鼠Kupffer细胞和SECs产生的IL-6和TNF-α减少。肝切除后，肝硬变大鼠肝窦内微血栓形成明显增加，血浆IL-6和TNF-α水平较对照组显著升高。此外，与对照组相比，肝硬变大鼠SECS中PS的产生明显减少，而肝细胞中PS的产生显著增加。结论：肝硬变大鼠肝切除前后肝细胞和SECs中PS的表达受到不同程度的调节，PS的表达受局部释放的炎性细胞因子的调节，而SECs中PS的表达减少可能导致肝微血栓的形成，这是肝硬变患者术后常见的现象。
Background: Liver dysfunction caused by intrasinusoidal microthrombi is frequently observed in patients with cirrhosis after hepatectomy, but the mechanistic pathway remains unknown. Objective: In the present study, we evaluated the expression of protein S (PS) in hepatocytes and sinusoidal endothelial cells (SECs) from rats with dimethylnitrosoamine-induced cirrhosis before and after hepatectomy. Results: The plasma level of PS antigen was significantly decreased in cirrhotic rats as compared to control rats treated with vehicle. PS expression was significantly decreased in hepatocytes isolated from cirrhotic rats as compared to controls. In contrast, PS expression was significantly increased in SECs isolated from rats with cirrhosis as compared to controls. Interkeukin-6 (IL-6) upregulated the expression of PS in hepatocytes, and tumor necrosis factor-alpha (TNF-alpha) decreased its expression in SECs from both cirrhotic and normal rats. The production of IL-6 and TNF-alpha by Kupffer cells and SECs was decreased in rats with cirrhosis as compared to controls. After hepatectomy, microthrombus formation was markedly enhanced in sinusoids from rats with cirrhosis, and the plasma levels of IL-6 and TNF-alpha were significantly increased in rats with cirrhosis as compared to controls. Furthermore, PS production in SECs was decreased, whereas that in hepatocytes was significantly increased in cirrhotic rats as compared to controls. Conclusions: These findings suggest that PS expression is differently regulated in hepatocytes and SECs of rats with cirrhosis before and after hepatectomy, that the expression of PS is regulated by locally released inflammatory cytokines, and that decreased expression of PS in SECs may cause liver microthrombus formation, which is frequently observed in patients with cirrhosis after hepatectomy.