胡黄连苷II的抗脂质过氧化作用及对肝线粒体损伤的保护作用
Anti-lipid peroxidation and protection of liver mitochondria against injuries by picroside II.
作者信息
Gao Hua, Zhou Ya-Wei
机构信息
Department of Chemistry, College of Chemistry and Molecular Engineering, Beijing University, Beijing 100871, China.
出版信息
World J Gastroenterol. 2005 Jun 28;11(24):3671-4. doi: 10.3748/wjg.v11.i24.3671.
AIM
To investigate the anti-lipid peroxidation and protection of liver mitochondria against injuries in mice with liver damage by picroside II.
METHODS
Three animal models of liver damage induced by carbon tetrachloride (CCl(4): 0.1 mL/10 g, ip), D-galactosamine (D-GalN: 500 mg/kg, ip) and acetaminophen (AP: 0.15 g/kg, ip) were respectively treated with various concentrations of picroside II (5, 10, 20 mg/kg, ig). Then we chose the continuously monitoring method (recommended by International Clinical Chemistry League) to analyze serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) values, Marland method to detect the activity of manganese-superoxide dismutase (SOD) in liver mitochondria, TBA colorimetry to determine the content of malonicdialdehyde (MDA) in liver tissue, DTNB method to evaluate the activity of glutathioneperoxidase (GSH-Px) and Lowry method to detect protein level in liver tissue. Meanwhile, effects of picroside II on the activity of ATPase and swelling extent of mitochondria in hepatocytes damaged by AP were also evaluated.
RESULTS
Picroside II could significantly prevent liver toxicity in the three models of liver damage. It decreased the high levels of ALT and AST in serum induced by the administration of CCl(4), D-GalN and AP, reduced the cellular damage of liver markedly, and appeared to be even more potent than the positive control drug of biphenyl dimethyl dicarboxylate pilules (DDB). In groups treated with different doses of picroside II, compared to the model group, the content of MDA in serum decreased evidently, whereas the content of SOD and GSH-Px increased in a dose-dependent manner, and the difference was statistically significant. Further, in the study of AP model, picroside II inhibited AP-induced liver toxicity in mice, enhanced the activity of ATPase, improved the swelling extent of mitochondria and helped to maintain a normal balance of energy metabolism.
CONCLUSION
Picroside II can evidently relieve hepatocyte injuries induced by CCl(4), D-GalN and AP, help scavenge free radicals, protect normal constructions of mitochondria membrane and enhance the activity of ATPase in mitochondria, thereby modulating the balance of liver energy metabolism, which might be part of the mechanisms of hepatoprotective effects of picroside II.
目的
研究胡黄连苷II对肝损伤小鼠的抗脂质过氧化作用及对肝线粒体的保护作用。
方法
分别用不同浓度的胡黄连苷II（5、10、20mg/kg，灌胃）处理四氯化碳（CCl₄：0.1mL/10g，腹腔注射）、D-半乳糖胺（D-GalN：500mg/kg，腹腔注射）和对乙酰氨基酚（AP：0.15g/kg，腹腔注射）诱导的三种肝损伤动物模型。然后我们选择连续监测法（国际临床化学联盟推荐）分析血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）值，用Marland法检测肝线粒体中锰超氧化物歧化酶（SOD）的活性，用TBA比色法测定肝组织中丙二醛（MDA）的含量，用DTNB法评估谷胱甘肽过氧化物酶（GSH-Px）的活性，用Lowry法检测肝组织中的蛋白质水平。同时，还评估了胡黄连苷II对AP损伤的肝细胞中ATP酶活性和线粒体肿胀程度的影响。
结果
胡黄连苷II能显著预防三种肝损伤模型中的肝毒性。它降低了CCl₄、D-GalN和AP给药诱导的血清中ALT和AST的高水平，明显减轻了肝脏的细胞损伤，且似乎比阳性对照药联苯双酯滴丸（DDB）更有效。在不同剂量胡黄连苷II处理组中，与模型组相比，血清中MDA含量明显降低，而SOD和GSH-Px含量呈剂量依赖性增加，差异有统计学意义。此外，在AP模型研究中，胡黄连苷II抑制了AP诱导的小鼠肝毒性，增强了ATP酶活性，改善了线粒体肿胀程度，有助于维持能量代谢的正常平衡。
结论
胡黄连苷II能明显减轻CCl₄、D-GalN和AP诱导的肝细胞损伤，有助于清除自由基，保护线粒体膜的正常结构，增强线粒体中ATP酶的活性，从而调节肝脏能量代谢平衡，这可能是胡黄连苷II保肝作用机制的一部分。
Zotero 插件