Motomura K, Sakai H, Isobe H, Nawata H
Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Gastroenterol Hepatol. 1997 Dec;12(12):887-92. doi: 10.1111/j.1440-1746.1997.tb00388.x.
All-trans retinoic acid (ATRA) has been reported to exert major effects on the immune system, including monocytes/macrophages. The present study was designed to determine whether ATRA would modulate macrophage-associated liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) in rats. All-trans retinoic acid administration alleviated the liver injury and reduced the incidence of death following hepatic failure. Serum alanine aminotransferase (ALT) levels 5 h after, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134+/-119 IU/L and 72.7%) compared with the control group (713+/-411 IU/L and 18.2%; P< 0.05). Histological findings supported these results. These effects may be due to suppression of tumour necrosis factor-alpha (TNF-alpha) and superoxide anions produced by activated macrophages. Serum levels of TNF-alpha 1 h after LPS administration were significantly lower in the ATRA-treated group (60.5+/-7.0 ng/mL) as compared with the control group (105.2+/-39.3 ng/mL; P< 0.05). Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, also suggested suppression of the release of superoxide anions from hepatic macrophages. These results suggest that ATRA acts as an immunomodulator in liver injury by suppressing the activation of liver macrophages.
据报道，全反式维甲酸（ATRA）对免疫系统有重大影响，包括对单核细胞/巨噬细胞。本研究旨在确定ATRA是否会调节由痤疮丙酸杆菌和脂多糖（LPS）诱导的大鼠巨噬细胞相关肝损伤。给予全反式维甲酸可减轻肝损伤，并降低肝衰竭后的死亡率。与对照组（713±411 IU/L和18.2%；P<0.05）相比，ATRA治疗组在给予LPS后5小时的血清丙氨酸转氨酶（ALT）水平（134±119 IU/L）和12小时内的存活率（72.7%）显著降低。组织学结果支持了这些结果。这些作用可能是由于抑制了活化巨噬细胞产生的肿瘤坏死因子-α（TNF-α）和超氧阴离子。与对照组（105.2±39.3 ng/mL；P<0.05）相比，ATRA治疗组在给予LPS后1小时的血清TNF-α水平显著降低（60.5±7.0 ng/mL）。用硝基蓝四唑灌注肝脏产生的甲臜沉积也表明肝巨噬细胞中超氧阴离子的释放受到抑制。这些结果表明，ATRA通过抑制肝巨噬细胞的活化而在肝损伤中起免疫调节作用。
