鲍氏威酸抗急性白血病裸鼠血管新生的实验研究

Experimental Study of the Effect of Boswellic Acid on Angiogenesis in Nude Mice with Acute Leukemia

【目的】观察鲍氏威酸对急性白血病裸鼠血管新生的影响。【方法】对25只裸鼠行3Gy60Coγ射线照射24 h后,选用急性白血病细胞株HL60细胞(4×106/只)腹腔接种裸鼠建立急性白血病的动物模型,用50 mg/(kg.d),100 mg/(kg.d),200 mg/(kg.d)不同剂量鲍氏威酸灌胃给药30 d,石蜡包埋骨髓病理切片免疫组化法观察裸鼠骨髓微血管密度变化,ELISA法检测药物作用后裸鼠血浆血管内皮生长因子(VEGF)的浓度。【结果】100 mg/(kg.d)及200 mg/(kg.d)组骨髓MVD为(18.00±3.54)个/HP,(12.80±2.59)个/HP;与未治疗组骨髓MVD(26.80±2.17个/HP)比较有显著差异。VEGF浓度为(18.60±0.89)ng/mL、(12.28±0.85)ng/mL,与阴性对照组VEGF浓度(27.16±1.16 ng/mL)比较有显著差异;50 mg/(kg.d)治疗组与阴性对照组比较无显著性差异。【结论】鲍氏威酸能降低裸鼠体内VEGF分泌及体内骨髓微血管密度,二者有比较密切的关系,鲍氏威酸抗白血病血管新生作用可能是通过VEGF起作用。

[Objective] To investigate the effect of boswellic acid on angiogenesis in nude mice with acute leukemia. [Methods]All 25 nude mice accepted a single dose of 3Gy γ-irradiation. HL60 cells, a human acute leukemic cell line, were implanted intraperitoneally by injection （2×10^7/ml, 0. 2ml, respectively） for 24 hours after irradiation. Twenty five nude mice were randomly divided into 5 groups （5 for each group） and feed for 30 days. Mice in negative control group received alcohol 0.5ml once a day while the one in positive control group received all-trans retinoic acid 0.3mg by intragastric administration. Three experimental groups were treated with boswellic acids of 50, 100, 200 mg/kg·d, respectively by intragastric administration. Mi- crovessel density （MVD） of bone marrow in mice was observed with immunohistochemical method and the plasma concentration of vascular endothelial growth factor （VEGF） in mice was measured with ELISA. [Results]MVD of bone marrow in experimental group of boswellie acid with 100, 200 mg/kg·d was 18.00 3. 54/HP and 12.80 2.59/HP, respectively. Serum concentration of VEGF in experimental group of hoswellic acid with 100 and 200mg/kg·d was 18.60 0.89 and 12.28 0.85ng/ml, respectively. The MVD and the concentration of VEGF in the boswellic acid treatment group with 100 and 200mg/kg·d were significantly lower than those in negative control group in statistics. There was no significant difference in MVD and VEGF between boswellic acid treatment group with 50mg/kg ·d and negative control group. [Conclusion] Boswellic acid can reduce the concentration of VEGF in plasma of nude mice. Meanwhile, the MVD of bone marrow is decreased. There is a close relation between MVD and VEGF. The anti-angiogenic function induced by the boswellic acids may be from the inhibition of VEGF.