1,3-二苯-1,3-丙二酮对二甲基亚硝胺致小鼠急性肝损伤的保护作用

目的 探讨1,3-二苯-1,3-丙二酮（DPPD）对二甲基亚硝胺（DMN）急性肝损伤的保护作用.方法 小鼠按体重随机平均分为五组,分别为对照组、DMN组和三组剂量组.剂量组分别经口灌胃给予小鼠DPPD 100、200、400 mg/kg体重每日1次,连续4d,然后腹腔注射给予致肝毒性剂量DMN（22 mg/kg体重）.染毒后24h测定血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和乳酸脱氢酶（LDH）活性;制备肝匀浆,改良Hission法测定肝中还原型谷胱甘肽（GSH）、氧化型谷胱甘肽（GSSG）含量,TBA法测定肝中丙二醛（MDA）含量;HE染色处理肝脏组织切片,光镜观察病理学改变.结果 与单独给予DMN组相比,给予DPPD组明显改善了DMN引起体重降低的现象,DMN＋DPPD高剂量组[（24.3±1.5）g]与DMN组[（22.7±1.0）g]相比,差异有统计学意义（P＜0.05）;并且显著降低血清中ALT、AST、LDH含量,DMN ＋DPPD高剂量组[ALT：（151±38）U/L,AST：（216±131）U/L,LDH：（1423±813）U/L]与DMN组相比[ALT：（1481±575） U/L,AST：（1155±559） U/L,LDH：（3196±784） U/L],差异有高度统计学意义（P＜0.01）.相比单独给予DMN组,给予DPPD组肝脏病理损伤明显改善,并呈一定的剂量效应关系.进一步研究表明,预防性给予DPPD各组可改善DMN引起的肝脂质过氧化现象,且相比单独给予DMN组,给予DPPD组的GSH/GSSG比值显著增加,DMN＋DPPD高剂量组（10.734±0.572）与DMN组（6.873±0.587）相比,差异有高度统计学意义（P＜0.01）.结论 DPPD可有效抵抗DMN对ICR小鼠肝脏造成的毒性损伤,调动机体抗氧化应激系统为可能的机制..

Protective effects of 1, 3-diphenyl-1, 3-propanedione on Dimethylnitrosamine-induced liver injury in mice

Objective To examine the protective effects of 1,3-liphenyl-1,3-proanedione （DPPD） on Dimethylnitrosamine （DMN）-induced hepatotoxicity on ICR mice.Methods Mice were randomly divided into 5 groups as follows：control group,DMN group and three dosage groups.Three dosage groups administered in intragastrically with DPPD at doses of 100,200 and 400 mg/kg body weight respectively for 4 d.24 hours after DMN injection （22 mg/kg body weight）,the serum enzyme including alanine aminotransferase （ALT）,aspartate aminotransferase （AST）,lactate dehydrogenase （LDH） were measured.The content of reduced glutathione （GSH） and oxidized glutathione （GSSG） were examined by Hisssion method,and the content of malondialdehyde （MDA） was examined by TBA method.Histopathological analysis were also made to observe the pathological chagne.Results Compared with DMN group,DPPD administration restored the body weight to normal,the difference between the DMN＋DPPD highest dose group [（24.3±1.5） g] and DMN group [（22.7±1.0） g] was statistically significant （P 〈 0.05）; and significantly decreased the serum of ALT,AST and LDH,the differences between the DMN＋DPPD highest dose group [ALT：（151±38） U/L,AST：（216±131） U/L,LDH：（1423±813） U/L] and DMN group [ALT：（1481±575） U/L,AST：（1155±559） U/L,LDH：（3196±784） U/L] were statistically significant （P 〈 0.01）.Liver histopathological examination showed that DPPD administration antagonized DMN-induced liver pathological damage in a dose-dependent manner.Further tests showed that DPPD significantly reduced the hepatic lipid peroxidation induced by DMN,and the ratio of GSH/GSSG was induced significantly by DPPD to antagonize DMN-induced hepatotoxicity,the difference between the DMN＋DPPD highest dose group （10.734±0.572） and DMN group （6.873±0.587） was statistically significant （P 〈 0.05）.Conclusion DPPD can effectively protect ICR male mice from DMN-induced hepatotoxicity.Reduction of oxidative stress may be part of the protection mechanism.