摘要
目的研究双环醇对小鼠慢性酒精性肝损伤的影响.方法小鼠连续4周给予5%酒精Lieber-Decarli全营养液体饮食,建立慢性酒精性肝损伤模型.动物于造模前和造模后口服双环醇每日1次,连服2～4周.末次给药后24 h 测定血清丙氨酸氨基转移酶(ALT)、胆固醇、低/高密度脂蛋白(HDL/LDL)和肝脏甘油三酯(TG),肝脏二甲基亚硝胺脱甲基酶(NDMA-DM),谷胱甘肽(GSH)及谷胱甘肽-巯基转移酶(GST)、谷胱甘肽还原酶(GR)、乙醛脱氢酶(ALDH)水平以及病理形态改变. 结果双环醇(200/300 mg*kg-1*d-1,连服2～4周)可明显抑制酒精引起的血清ALT和NDMA-DH的升高和肝脏GSH、GST、GR、ALDH的减低,使其恢复至正常水平.此外,双环醇还可使肝脏升高的TG下降28%～34%,提高血清HDL水平(68%～98%),降低LDL(33%～42%).肝脏脂肪性变也明显减轻,双环醇预防给药组(300 mg*kg-1*d-1)小鼠肝脏病理积分为1.4±1.2,双环醇治疗给药组(300 mg*kg-1*d-1)小鼠肝脏病理积分为0.7±0.5,与模型组比较,差异均有统计学意义(分别P＜0.05,P＜0.01﹚.结论双环醇对小鼠慢性酒精性肝损伤具有明显的保护作用,其作用机制与减轻肝脏脂肪堆积,加速乙醇和乙醛的清除以及提高肝脏抗氧化能力相关.
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 300kg^-1·d^-1was 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 300kg^-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 300kg^-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.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2005年第48期3409-3413,共5页
National Medical Journal of China
基金
科技部"973"国家重点科技攻关计划基金资助项目(2004CB518908)
