柚皮素对四氯化碳致小鼠化学性肝损伤中氧化应激介质生成影响的实验研究  

Eexperimental study on the effect of naringenin on oxidative stress medium generated in carbon tetrachloride-induced chemical hepatic injury in mice

作　　者：李桃园[1,2,3] 王昕[1] 赵旋 李丹[1] 王淑梅[1] 章国良[1] 

机构地区：[1]北京大学医学部基础医学院药理系,北京100191 [2]北京大学医学部药学院药理系,北京100191 [3]北京市垂杨柳医院药剂科

出　　处：《中国临床药理学杂志》2010年第6期420-423,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(30973585);科技部创新药物综合性研究开发技术平台建设课题基金资助项目(2009ZX09301-010)

摘　　要：目的考察柚皮素(黄酮类化合物)对小鼠化学性肝损伤中氧化应激介质生成的影响。方法用灌胃法,小鼠连续7天预给予柚皮素(25,50,100mg·kg-1),第7日经腹腔单次注射四氯化碳(CC l4,1mL·kg-1)诱发化学性肝损伤。24h后用紫外分光光度法测定血清转氨酶(ALT、AST)水平,氧化应激介质丙二醛(MDA)含量,及肝微粒体超氧化物歧化酶(SOD)活性;用单细胞凝胶电泳法检测肝细胞中DNA氧化损伤水平。结果与对照组相比,CCl4化学损伤组小鼠的血清ALT水平显著升高,氧化应激介质生成增多,肝细胞DNA氧化损伤断裂显著增多。柚皮素预处理组,CCl4急性肝损伤中血清转氨酶水平虽然未见明显变化,但柚皮素在其高剂量组(100mg·kg-1)可使MDA水平有下降趋势,SOD活性有升高趋势且可显著性地降低CCl4损伤所致彗星拖尾细胞的百分率。结论预先给予柚皮素(25,50,100mg·kg-1)可使CCl4所致急性肝损伤中氧化应激反应减轻,并可显著降低肝细胞核DNA单链断裂氧化损伤水平。Objective To investigate the effect and the possible mecha- nism of naringenin（Nar） on oxidative stress medium generated in carbon tetrachloride- induced chemical hepatic injury in mice. Methods Nar were intragastric administered once daily for 7 days （25,50,100 mg·kg^-1）. After the last administation of Nar, chemical hepatic injury was induced by once intraperitoneal injection of CCl4 （ 1 mg ·kg^-1 ） in mice. After 24 hours the levels of serum aspartate（ALT） and alanine transaminases （ AST）, hepatic malondialdehyde （ MDA ） and superoxide dismutase （SOD） were detected by colorimetric method. DNA oxidative damage was detected by single cell gel electrophoresis. Results Compared with control group, CCI4 treatment significantly increased the levels of serum transaminase ALT （P 〈0. 01 ）, oxidative stress medium MDA, and DNA fragmentation （P 〈 0. 01 ） were observed in CCl4 - stimulated mice. Pretreatment of Nar slightly inhibited MDA generation, and increased the activity of SOD. Moreover, in the range of concentration from 25 mg ·kg^-1 to 100 mg·kg^-1, Nar significantly decreased DNA single strand breaks（ P 〈 0.01 ） induced by CCl4 -stimulated hepatocytes in mice. Conclusion The present results indicated that Nar could reduce the oxidative stress medium generated, against liver DNA breaks of oxidative damage.

关 键 词：柚皮素 四氯化碳化学性肝损伤 DNA氧化性损伤 

分 类 号：R962[医药卫生—药理学] R975.5[医药卫生—药学]