齐墩果酸抗大鼠移植性肝癌作用的研究

Study on Inhibitive Effect of Oleanolic Acid on Transplanted Hepatocarcinoma in Mice

[目的]研究齐墩果酸抗肿瘤作用以及对肿瘤血管内皮生长因子(VEGF)和微血管密度(MVD)的影响,探讨齐墩果酸抗肝癌作用机制。[方法]32只大鼠移植性肝癌模型随机分为齐墩果酸高剂量组(100 mg/kg.d)、齐墩果酸低剂量组(50 mg/kg.d)、氟尿嘧啶(5-Fu)组(5 mg/kg.d)、生理盐水组,每组8只,前3组于造模成功后第8天腹腔注射给药,生理盐水组灌胃给药,连续用药14 d后停药24h,取血处死大鼠,取出瘤块称重,常规瘤体组织形态学观察,分离血清检测肝功能指标谷草转氨酶(AST)、谷丙转氨酶(ALT),用免疫组化法检测瘤块中VEGF和MVD的表达情况。[结果]齐墩果酸给药组瘤重明显低于生理盐水对照组,与生理盐水对照组比较差异显著(P<0.01);齐墩果酸给药组及5-Fu组血管条数目密集程度较生理盐水组明显减少;齐墩果酸对血清中AST、ALT活性升高有明显的拮抗作用,并且AST的含量与生理盐水对照组比较有显著性差异(P<0.01);造模各组VEGF及MVD的表达水平均明显高于空白组(P<0.01),两者的表达均以生理盐水组最高。[结论]齐墩果酸可显著抑制大鼠体内癌细胞的生长,对移植性肝癌所造成的肝功能损伤具有明显的保护作用,其作用机制可能与下调VEGF和MVD的表达水平有关。

[ Objective J To research the effect of oleanolic acid （OA） on vascular endothelial growth factor （VEGF） and microvessel density （MVD）, and investigate its anti -cancer mechanism. [ Methods] 32 mice were randomly divided into 4 groups,i, e. oleanolic acid high dose group （ 100 mg/kg, d）, oleanolic acid low dose group （50 mg/kg·d）, fluorouracil group （ 5 - Fu ） （ positive control, 50 mg/kg ＂d）, and normal saline group （negative control）. The mice in former three model groups were administered by intraperitoneal injection and those in normal saline group were intragastric administrated on the 8^thday for 14d. After stopping administration,the tumor blocks were taken out of the mice on the next day and carried out routine organization morphological observation,in the mean time,liver function indexes AST and ALT were detected, VEGF and MVD in tumor were determined by immunohistochemical method. [ Result] The tumor weights in OA groups were obvious lower than that in normal saline control group,and the difference between which was significant （P 〈0.01 ） ; the intensive degree of vascular in OA group and 5 - Fu were obvious lower compared with that in normal saline group. Oleanolic acid could inhibit the activities of AST and ALT effectively,and the contents of AST in OA groups were much higher than that in normal saline group with significant difference （ P 〈 0.01 ）. The expression levels of VEGF and MVD in model groups were significantly higher that in blank control group （P 〈 0.01 ） ,and which were the highest in normal saline group. [ Conclusion] Oleanolic acid can inhibit the growth of cancer cell in vivo significantly and repair the liver damage caused by transplanted hepato- carcinoma,and its anti -cancer mechanism may be related to the expression of VEGF and MVD.