黄芪甲甙胸腔注射对肺癌小鼠恶性胸腔积液的影响

Effect of Astragaloside Ⅳ Intrapleural Injection on Malignant Pleural Effusion in Lung Cancer Mice

目的:探讨黄芪甲苷(astragaloside Ⅳ,AsⅣ)胸腔注射对肺癌小鼠恶性胸腔积液(malignant pleural effusion,MPE)的影响。方法:BALB/C小鼠100只,胸腔注射Lewis肺癌细胞建立Lewis肺癌恶性胸腔积液模型后,将100只小鼠按随机数字法分为五组,每组20只。A组:阴性对照,注射0.9%生理盐水(NS);B组:阳性对照,注射顺铂(DDP)0.5 mg/kg;C组:低剂量黄芪甲苷(l-AsⅣ)0.3 mg/kg;D组:中剂量的黄芪甲苷(m-AsⅣ)1.0 mg/kg;E组:高剂量黄芪甲苷(h-AsⅣ)3.0 mg/kg。接瘤24 h后采用胸腔穿刺注射药物的给药方式。比较五组治疗效果、血管内皮生长因子(vascular endothelial growth factor,VEGF)含量及VEGF、水通道蛋白-1(AQPs-1)的表达水平。结果:B、D、E组胸腔积液量均少于A组(P<0.01),瘤细胞存活率和瘤细胞数均低于A组(P<0.01),胸膜转移瘤最大结节直径均小于A组(P<0.01),上述指标都存在剂量依赖性。E组胸腔积液量、瘤细胞存活率、最大结节直径均低于B组,抑瘤率高于B组(P<0.05)。B、C、D、E组VEGF含量均低于A组(P<0.01),且存在剂量依赖性。B、C、D、E组VEGF表达均低于A组(P<0.01),C、D、E组AQP-1蛋白表达均低于A组(P<0.05、<0.05、<0.01)。结论:AsⅣ胸腔注射可以抑制Lewis肺癌细胞生长,减少恶性胸腔积液生成,其机制可能与抑制VEGF及AQPs-1表达有关。

Objective:To investigate the effect of astragaloside Ⅳ(AsⅣ)intrapleural injection on malignant pleural effusion(MPE)in lung cancer mice.Method:After 100 BALB/C mice were injected with Lewis lung cancer cells to establish Lewis lung cancer MPE model,100 mice were divided into five groups according to random number method,with 20 mice in each group.Group A:negative control,injected with 0.9% normal saline(NS);group B:positive control,injected with Cisplatin(DDP)0.5 mg/kg;group C:low dose astragaloside Ⅳ(l-AsⅣ)0.3 mg/kg;group D:medium dose of astragaloside Ⅳ(m-AsⅣ)1.0 mg/kg;group E:high dose astragaloside Ⅳ(h-AsⅣ)3.0 mg/kg.The drug was injected by thoracic puncture 24 hours after tumor grafting.The therapeutic effect,the content of vascular endothelial growth factor(VEGF),the expression of VEGF and aquaporin-1(AQPs-1)were compared.Result:The pleural water volume in group B,D and E was less than that in group A(P<0.01),the survival rate and number of tumor cells were lower than those in group A(P<0.01),and the maximum nodule diameter of pleural metastasis was less than that in group A(P<0.01).The above indexes were dose-dependent.The pleural water volume,tumor cell survival rate and maximum nodule diameter in group E were lower than those in group B,and the tumor inhibition rate was higher than that in group B(P<0.05).The content of VEGF in group B,C,D and E was lower than that in group A(P<0.01),and there was a dose-dependent relationship.The expression of VEGF in group B,C,D and E was lower than that in group A(P<0.01),and the expression of AQP-1 protein in groups C,D and E was lower than that in group A(P<0.05,<0.05,<0.01).Conclusion:As Ⅳ intrapleural injection can inhibit the growth of Lewis lung cancer cells and reduce the formation of MPE.Its mechanism may be related to the inhibition of VEGF and AQPs-1 expression.