口服齐墩果酸对D-氨基半乳糖致小鼠急性肝损伤的保护作用

Hepatoprotective effect of oleanolic acid on D- galactosamine- induced acute liver injury in the mice

目的研究口服齐墩果酸(OA)对D-氨基半乳糖诱导小鼠急性肝损伤的保护作用。方法将♂昆明种小鼠随机分为对照组、OA给药组、模型组、OA预处理组。采用ig给予OA给药组和OA预处理组小鼠200μmol·kg-1OA,ig给予对照组、模型组等体积菜籽油,每天2次,连续3 d,末次给药1 h后,ip给予对照组、OA给药组等体积生理盐水,ip给予模型组和OA预处理组800 mg·kg-1D-氨基半乳糖溶液造模,造模8 h后,收集各组小鼠的血液和肝脏组织,测定小鼠血清中天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)和肝脏中丙二醛(MDA)的含量,观察肝组织病理学的改变,并应用实时定量RT-PCR检测肝毒性相关基因的表达水平。结果 OA预处理能降低D-氨基半乳糖所致小鼠血清中AST、ALT的活性及肝组织中MDA的含量,明显改善肝细胞坏死病变的程度,并逆转小鼠急性肝损伤所致的生长停滞及DNA损伤诱导基因153(Chop10)、生长停滞及DNA损伤诱导基因45、Egr1、m KC、TNF-αm RNA表达的增高。结论 OA对D-氨基半乳糖所致小鼠急性肝损伤具有保护作用,其机制可能与缓解急性内质网应激、减轻炎症和抗氧化有关。

OBJECTIVE To investigate the protective effect of oleanolic acid（ OA） on D- galactosamine- induced acute liver injury in mice. METHODS Mal Kunming mice were radomly divided into 4 groups： control group,OA group,model group,OA pretratment group. Male mice were treated with OA（ 200 μmol·kg^- 1,dissolved in vegetable oil,ig）,control group and model group were intragastrical administrated（ ig） with rapeseed oil of the same volume. twice per day for 3 days. One hour after the last dose,control group and OA group were theated with saline of the same volume by ip,model group and o A pretreatment group were administrated D-glactosamine（ 800 mg·kg^- 1,ip） to establish model. Eight hours later,blood and livers were collected. Liver injury was evaluated by serum alanine aminotransferase（ ALT）,aspirate aminotransferase（ AST） activities,content of MDA in liver,histopathological changes,and the expression of toxicity related genes determined by real- time RT- PCR. RESULTS D- galactosamine significantly increased serum levels of ALT,AST and liver MDA content. Pretreatment of OA decreased ALT,AST and MDA levels,and significantly improved the severity of liver cell necrosis. OA attenuated the increase of m RNA expression of D- galactosamine- induced growth- arrest-and- DNA- damageinducible gene- 153（ GADD153,Chop10）,GADD45,early growth response protein- 1（ Egr1）,mouse keratinocyte- derived chemokine（ mKC） and tumor necrosis factor（ TNF- α）. CONCLUSION OA is effective in protecting against Dgalactosamine- induced acute liver injury. The mechanisms appear to be due,at least part,to attenuated ER stress,and decreased inflammation and oxidative stress.