血供阻断治疗对肺癌兔模型新生血管生成的影响及相关机制

Effect of blood supply blocking therapy on angiogenesis of lung cancer rabbit model and related mechanisms

目的探讨血供阻断治疗兔肺癌对新生血管的影响。方法纯种新西兰大白兔30只,普通级,雌雄不限,4~6月龄,平均分为3组:空白组、肺癌组与阻断组,每组各10只。空白组不建立兔肺癌模型,肺癌组与阻断组均建立肺癌模型,然后阻断组给予血供阻断治疗,肺癌组给予PBS治疗。记录肺癌组与阻断组大白兔的成瘤情况;记录3组的病理积分;检测3组在实验前(T_(1))、造模后4周(T_(2))与阻断后4周(T_(3))等3个时间点血清白细胞介素(IL)-6、IL-8水平;观察3组新生血管形成(MVD)与血管内皮生长因子(VEGF)表达情况。结果肺癌组与阻断组T_(2)时间点的肿瘤体积对比,差异无统计学意义(P>0.05),阻断组T_(3)时间点的肿瘤体积为(1.66±0.18)cm^(3),低于肺癌组[(3.18±0.21)cm^(3)],差异有统计学意义(P<0.05)。对照组、肺癌组、阻断组病理积分分别为(0.23±0.01)、(2.82±0.18)、(1.34±0.022)分,差异有统计学意义(P<0.05)。对照组肺组织病理学形态与细胞状态正常;肺癌组肿瘤细胞呈浸润性生长,与周围正常肺组织界限不清;阻断组肿瘤细胞排列紧密呈实体巢状,间质结缔组织少。肺癌组与阻断组T_(2)、T_(3)时间点的血清IL-6、IL-8水平均高于T_(1)时间点,也均显著高于对照组,差异有统计学意义(P<0.05),阻断组T_(3)时间点的血清IL-6、IL-8水平为(23.02±4.19)、(8.72±2.13)ng/mL,低于肺癌组[(33.20±4.30)、(12.82±1.77)ng/mL],差异有统计学意义(P<0.05)。肺癌组与阻断组的MVD与VEGF表达水平为(79.13±5.01、0.89±0.10)(47.77±4.92、0.56±0.09),均显著高于对照组(32.82±4.56、0.34±0.04),阻断组低于肺癌组,差异均有统计学意义(P<0.05)。结论兔肺癌多伴随有新生血管形成与VEGF的高表达,血供阻断能抑制新生血管形成与VEGF的表达,也可抑制炎症因子的释放,从而发挥重要的治疗作用。

Objective To investigate the effect of blood supply blockade on neovascularization in rabbit lung cancer.Methods Thirty purebred New Zealand white rabbits were equally divided into three groups:blank group,lung cancer group and blocking group,10 rabbits in each group.The blank group were not established rabbit lung cancer model,the lung cancer group and the blocking group both establishedlung cancer model,and then the blocking group were given blood supply blockade,and the lung cancer group were treated with PBS.The tumor formation of the white rabbits in the lung cancer group and the blocking group was recorded.The pathological scores in the 3 groups were recorded.Serum interleukin(IL)-6 and IL-8 levels were detected in the three groups before the experiment(T_(1)),4 weeks after modeling(T_(2)),and 4 weeks after blocking(T_(3)).Microvessel density(MVD)and vascular endothelial growth factor(VEGF)expression in the 3 groups were observed.Results There were no significant difference in tumor volume between the lung cancer group and the blocking group at T_(2) time point(P>0.05),and the tumor volume at the T_(3) time point in the blocking group was(1.66±0.18)cm^(3),which was lower than that in the lung cancer group[(3.18±0.21)cm^(3)],the difference was statistically significant(P<0.05).The pathology scores of the control group,lung cancer group,and blocking group were(0.23±0.01),(2.82±0.18),(1.34±0.022)points,respectively,and the difference was statistically significant(P<0.05).The pathological morphology and cell status of the lung tissue in the control group were normal,the tumor cells in the lung cancer group were showed invasive growth and were indistinguishable from the surrounding normal lung tissues,the tumor cells in the blocking group were closely arranged in nest,and the interstitial connective tissue were less.The levels of serum IL-6 and IL-8 at the T_(2),T_(3) times points in the lung cancer group and the blocking group were higher than those in the T_(1) time point(P<0.05),which were also significantly higher than in the control group(P<0.05).The levels of serum IL-6 and IL-8 at the T_(3) time point in the blocking group were(23.02±4.19)and(8.72±2.13)ng/mL,which were lower than those in the lung cancer group[(33.20±4.30),(12.82±1.77)ng/mL],the differences were statistically significant(P<0.05).The levels of MVD and VEGF expression in the lung cancer group and the blocking group were 79.13±5.01,0.89±0.10,and 47.77±4.92,0.56±0.09,which were significantly higher than those in the control group(32.82±4.56,0.34±0.04),and the blocking group were lower than those in the lung cancer group,the difference were statistically significant(P<0.05).Conclusion Rabbit lung cancer is associated with high angiogenesis and high expression of VEGF.Blood supply blockade can inhibit the formation of angiogenesis and VEGF,and also inhibit the release of inflammatory factors,thus plays important therapeutic role.