Pan Zhihong, Dan Zili, Fu Yu, Tang Wangxian, Lin Jusheng
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2006;26(5):508-12. doi: 10.1007/s11596-006-0505-8.
The effects of all-trans-retinoic acid (ATRA) in low doses supplementation on concentrations of polar retinoid metabolites (PRM) and retinoids in the ethanol-fed rat liver, and on hepatocyte injury were investigated. The rat model of alcoholic liver disease (ALD) was induced by intragastric infusion of ethanol, and then the rats were administrated with ATRA in two different doses (150 microg/kg body weight and 1.5 mg/kg body weight) for 4 weeks. Concentrations of retinoids in rat liver and plasma were determined by using HPLC. Liver tissues pathologic changes were observed under the light microscopy and electron microscopy. The serum transaminases concentrations were measured. The results showed that the HPLC analysis of retinoids revealed that retinoids (vitamin A, RA, retinyl palmitate) concentrations in ethanol-fed rat liver and RA concentration in ethanol-fed rat plasma were markedly diminished (P<0.01) after ethanol feeding for 12 weeks. Furthermore, obvious peaks of PRM were formed in livers of ethanol-fed rats. ATRA 150 microg/kg supplementation in ethanol-fed rats for 4 weeks raised RA concentration in both liver and plasma, and also raised vitamin A concentration in liver to control levels, partially restored retinyl palmitate concentration (P<0.05) in liver. ATRA 1.5 mg/kg supplementation raised not only RA concentrations in liver and plasma but also retinyl palmitate concentrations in liver. However, the vitamin A concentration in liver of ATRA-supplemented rats (1.5 mg/kg) was higher than that of controls (P<0.05). The histologic observation of liver tissues indicated that ATRA treatment notably alleviated hepatocellular swelling, steatosis, the swelling of mitochondria and proliferation of smooth endoplasmic reticulum (SER). ATRA treatment greatly decreased levels of serum transaminases as compared with the only ethanol-fed group (P<0.05). It was concluded that low-dose ATRA treatment could restore retinoids concentrations and abolish the PRM formation in liver of ALD rats, and then ameliorate the injury of liver cells.
研究了低剂量补充全反式维甲酸（ATRA）对乙醇喂养大鼠肝脏中极性类视黄醇代谢物（PRM）和类视黄醇浓度以及肝细胞损伤的影响。通过胃内输注乙醇诱导酒精性肝病（ALD）大鼠模型，然后将大鼠分为两组，分别给予两种不同剂量的ATRA（150μg/kg体重和1.5mg/kg体重），持续4周。采用高效液相色谱法（HPLC）测定大鼠肝脏和血浆中的类视黄醇浓度。在光学显微镜和电子显微镜下观察肝脏组织的病理变化。测定血清转氨酶浓度。结果显示，HPLC分析类视黄醇发现，乙醇喂养12周后，乙醇喂养大鼠肝脏中的类视黄醇（维生素A、视黄酸、棕榈酸视黄酯）浓度和乙醇喂养大鼠血浆中的视黄酸浓度显著降低（P<0.01）。此外，乙醇喂养大鼠的肝脏中形成了明显的PRM峰。在乙醇喂养大鼠中补充150μg/kg的ATRA持续4周，可提高肝脏和血浆中的视黄酸浓度，还可将肝脏中的维生素A浓度提高至对照水平，部分恢复肝脏中棕榈酸视黄酯的浓度（P<0.05）。补充1.5mg/kg的ATRA不仅提高了肝脏和血浆中的视黄酸浓度，还提高了肝脏中棕榈酸视黄酯的浓度。然而，补充ATRA（1.5mg/kg）的大鼠肝脏中的维生素A浓度高于对照组（P<0.05）。肝脏组织的组织学观察表明，ATRA治疗显著减轻了肝细胞肿胀、脂肪变性、线粒体肿胀和平滑内质网（SER）增生。与仅乙醇喂养组相比，ATRA治疗显著降低了血清转氨酶水平（P<0.05）。结论是，低剂量ATRA治疗可恢复ALD大鼠肝脏中的类视黄醇浓度，消除PRM形成，进而改善肝细胞损伤。
