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目的 研究川芎嗪联合顺铂对Lewis肺腺癌小鼠移植瘤生长及抑制血管生成的作用机制.方法 培养Lewis小鼠肺腺癌细胞,建立移植瘤模型.按照体重将成功制备的荷瘤小鼠模型随机分成4组,每组15只:模型组、顺铂组、川芎嗪组、联合组.模型组:0.9％ NaCL,顺铂组:2 mg·kg-1,川芎嗪组:100mg·kg-1,联合组:两种药物相加.均每次0.2 mL,干预2周.称量瘤重,计算抑瘤率;用免疫组化方法检测每组血管内皮生长因子(VEGF)、血管抑制蛋白(VASH-1)的表达.结果 给药后,联合组、顺铂组、川芎嗪组的抑瘤率分别为54.81％,32.36％,18.36％,与模型组(抑瘤率为0)比较,差异均有统计学意义(均P＜ 0.05).联合组、顺铂组、川芎嗪、模型组的VEGF表达分别为20.37 ±2.02,28.07±4.29,26.43±4.69,62.14±6.78;这4组的VASH-1表达分别为9.04±1.01,10.10±1.61,11.53±1.96,12.94±1.10,3个给药组与模型组相比,差异均有统计学意义(均P＜ 0.05).Pearson相关性分析:VEGF与VASH-1成正相关(r=0.664,P＜0.05).结论 川芎嗪联合顺铂协同抑制Lewis小鼠移植瘤生长,其作用机制可能为川芎嗪与顺铂可以直接作用癌细胞,同时降低VEGF与VASH-1表达,发挥抗血管生成作用.“,”Objective To investigate the mechanism of tetramethylpyrazine combined with cisplatin on the transplanted tumor growth and angiogenesis inhibition of Lewis lung adenocarcinoma in mice.Methods Lewis lung carcinoma model of C57BL/6 mice were produced by under arm injection of Lewis lung cancer cells.Then the tumor-bearing mice were randomized into fore groups,with 15 mouse in each group:model group,cisplatin group,tetramethylpyrazine (TMP) group and combined group(TMP + cisplatin).Control group was given with 0.9％ NaCL 0.2 mL,cisplatin group was given with 2 mg· kg-1 cisplatin 0.2 mL,TMP group was given with 100 mg · kg-1 TMP 0.2 mL,combination group was TMP + cisptatin groups,per 0.2 mL.All mouse were sacrificed after intraperitoneal injection for two weeks.Subcutaneous tumors were processed for tumor weight,and the tumor inhibitory rate was calculated.The expressions of vascular endothelial growth factor (VEGF)and Vasohibin-1 (VASH-1) were determined by immunohistochemistry.Results Compared with model group (tumor inhibition rate:0),tumor inhibition rate in combination group,cisplatin group,TMP group were 54.81％,32.36％,18.36％ with statistically significant difference between groups (all P ＜ 0.05).The expression levels of VEGF in combination group,cisplatin group,TMP group,model group were 20.37 ± 2.02,28.07 ± 4.29,26.43 ± 4.69,62.14 ±6.78,respectively.The expression levels of VASH-1 in the four groups were 9.04 ± 1.01,10.10± 1.61,11.53 ± 1.96,12.94 ± 1.10,with statistically significant difference between groups (all P ＜ 0.05).Pearson correlation analysis:the VEGF and VASH-1 was positively correlated (r =0.664,P ＜ 0.05).Conclusion Tetramethylpyrazine has synergetic inhibitory effect with cisplatin on transplanted tumor growth of Lewis lung carcinoma in mice.The action mechanism may be due to exert direct effects on cancer cell and down-regulate the VEGF and VASH-1 expression,inhibiting tumor angiogenesis.