[双环醇对小鼠酒精性肝损伤的保护作用]

Mo Cheng-lin, Li Ye, Li Yan

Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100050, China.

Zhonghua Yi Xue Za Zhi. 2005 Dec 21;85(48):3409-13.

OBJECTIVE

To study the protective effect of bicyclol on alcohol-induced liver injury in mice.

METHODS

Sixty male mice were randomly divided into 6 groups. Ten mice were fed with Lieber-Decarli liquid diet without alcohol and used as normal controls. Fifty mice were fed with Lieber-Decarli liquid diet containing 5% alcohol for four weeks so as to establish a model of alcohol-induced liver damage. Ten mice fed with Lieber-Decarli liquid diet containing 5% alcohol for four weeks were used as model group. Bicyclol in a dose of either 200 or 300 .kg(-1).d(-1) was given orally simultaneously with alcohol intake as prevention groups (10 mice in each group), and bicyclol in a dose of either 200 or 300 .kg(-1).d(-1) was given orally 2 weeks after the beginning of alcohol intake as treatment groups (10 mice in each group). Twenty-four hours after the last dose of bicyclol the mice were decapitated and then their blood samples and livers were taken. The serum alanine aminotransferase (ALT), cholesterol (CHOL), and high-density lipoprotein/low-density lipoprotein (HDL/LDL), and liver triglyceride (TG), N-nitrosodimethylamine demethylase (NDMA-DM), glutathione (GSH), glutathione S-transferase (GST), glutathione reductase (GR), and aldehyde dehydrogenase (ALDH) were determined by biochemical assays. The extent of liver damage was evaluated by histological examination.

RESULTS

Four weeks after alcohol intake the serum ALT and TG were 1.9 and 2.7 times those of the normal control group. The levels of liver TG of the bicyclol 200 kg(-1).d(-1) and 300 kg(-1).d(-1) treatment groups were significantly lower than that of the model group by 28% and 32% respectively (both P < 0.05). The levels of liver TG of the bicyclol 200 kg(-1).d(-1) and 300 kg(-1).d(-1) prevention groups were significantly lower than that of the model group by 32%, and 47% respectively (both P < 0.01). Pathological changes including steatosis and hepatocyte ballooning degeneration were found in the livers of the model group. The levels of liver GSH, GST, and GR in the model group decreased by 37%, 22%, and 19% in comparison with the normal control group. The levels of liver GSH and GST of the bicyclol prevention groups were normal, and the liver GR level was 1.2 times that of the normal control group. The liver NDMA-DM activity of the model group was 1.9 times that of the normal control group and was normal in the bicyclol prevention and treatment groups. The liver cytoplasmic ALDH level was 30% lower in the model group than in the normal control group (P < 0.05), and was 2.9 times in the bicyclol groups (P < 0.01). The serum cholesterol levels of the bicyclol groups were all significantly lower than that of the model group (all P < 0.01). The serum levels of HDL of the bicyclol prevention groups and treatment were all significantly lower than that in the model group (P < 0.01 or P < 0.05).

CONCLUSION

Bicyclol protects mice against alcohol-induced hepatotoxicity by reduction of hepatic steatosis and cellular damage, acceleration of alcohol and aldehyde elimination and anti-peroxidation.

目的

研究双环醇对小鼠酒精性肝损伤的保护作用。

方法

将60只雄性小鼠随机分为6组。10只小鼠给予不含酒精的Lieber - Decarli液体饲料，作为正常对照组。50只小鼠给予含5%酒精的Lieber - Decarli液体饲料4周，以建立酒精性肝损伤模型。10只给予含5%酒精的Lieber - Decarli液体饲料4周的小鼠作为模型组。以200或300 mg·kg⁻¹·d⁻¹的剂量在摄入酒精的同时口服双环醇作为预防组（每组10只小鼠），并以200或300 mg·kg⁻¹·d⁻¹的剂量在摄入酒精2周后口服双环醇作为治疗组（每组10只小鼠）。在末次给予双环醇24小时后，将小鼠断头，然后采集血液样本和肝脏。通过生化检测测定血清丙氨酸氨基转移酶（ALT）、胆固醇（CHOL）、高密度脂蛋白/低密度脂蛋白（HDL/LDL），以及肝脏甘油三酯（TG）、N - 亚硝基二甲胺脱甲基酶（NDMA - DM）、谷胱甘肽（GSH）、谷胱甘肽S - 转移酶（GST）、谷胱甘肽还原酶（GR）和醛脱氢酶（ALDH）。通过组织学检查评估肝损伤程度。

结果

摄入酒精4周后，血清ALT和TG分别是正常对照组的1.9倍和2.7倍。双环醇200 mg·kg⁻¹·d⁻¹和300 mg·kg⁻¹·d⁻¹治疗组的肝脏TG水平分别比模型组显著降低28%和32%（均P < 0.05）。双环醇200 mg·kg⁻¹·d⁻¹和300 mg·kg⁻¹·d⁻¹预防组的肝脏TG水平分别比模型组显著降低32%和47%（均P < 0.01）。模型组肝脏出现脂肪变性和肝细胞气球样变性等病理变化。模型组肝脏GSH、GST和GR水平与正常对照组相比分别降低37%、22%和19%。双环醇预防组肝脏GSH和GST水平正常，肝脏GR水平是正常对照组的1.2倍。模型组肝脏NDMA - DM活性是正常对照组的1.9倍，双环醇预防组和治疗组均正常。模型组肝脏细胞质ALDH水平比正常对照组低30%（P < 0.05），双环醇组是正常对照组的2.9倍（P < 0.01）。双环醇组血清胆固醇水平均显著低于模型组（均P < 0.01）。双环醇预防组和治疗组血清HDL水平均显著低于模型组（P < 0.01或P < 0.05）。