川芎嗪联合顺铂对Lewis肺腺癌小鼠抑制生长的作用

Inhibitory effect of Tetramethylpyrazine in combination with cisplatin on growth of Lewis lung adenocarcinoma in mice

目的观察川芎嗪联合顺铂对Lewis肺腺癌小鼠瘤组织中的缺氧诱导因子1α(HIF-1α)、碱性成纤维细胞生长因子(b-FGF)、血管生成抑制蛋白(VASH-1)变化并探讨其抗肿瘤机制。方法将48只小鼠模型随机分成4组,对照组、顺铂组(2 mg·kg-1)、川芎嗪组(100 mg·kg-1)和联合组(顺铂组2mg·kg-1+川芎嗪组100 mg·kg-1),每组12只。给药2周,处死小鼠,称量瘤重,计算抑瘤率;用免疫组化法检测各组HIF-1α、b-FGF、VASH-1的表达。结果与对照组相比,实验组的抑瘤率均明显提高(P<0.05),联合组抑瘤率最高;与对照组相比,3个给药组的HIF-1α、b-FGF、VASH-1表达均明显降低(P<0.05)。HIF-1α与b-FGF成正相关(P<0.05),b-FGF与VASH-1成正相关(P<0.05),HIF-1α与VASH-1无相关。结论川芎嗪联合顺铂降低HIF-1α的表达,进而降低b-FGF与VASH-1的表达,协同抑制肿瘤生长。

Objective To observe the effect of Tetramethylpyrazine combined with cisplatin on Lewis lung adenocarcinoma by the change of hypoxia-inducible factor 1 alpha （ HIF -1α） , basic fibroblast growth factorb （ b-FGF） ,vasohibin-1 （ VASH-1 ） in mice tumor tissues and explore the mechanism of anti -tumor.Methods Forty -eight mice were randomly divided into 4 groups, control group, cisplatin group, Tetramethylpyrazine group and combined group, 12 rats in each group, cisplatin at a dose of 2 mg· kg^-1 , Tetramethylpyrazine at a dose of 100 mg· kg^-1 , combination group（ the doses as above）.All mice were sac-rificed after treatment for two weeks and these tumors were obtained.The weighed, and the tumor inhibitory was calculated.The expressions of HIF-1α, b -FGF and VASH -1 were determined by immunohisto-chemistry after two weeks administration.Results Compared with the control group, the tumor inhibition rate in experimental groups was signi-ficantly increased （ P〈0.05 ） , and was highest in combination group.The expression of HIF -1α, b -FGF and VASH -1 in the cisplatin group, Tetramethylpyrazine group and combined group were decreased obviously compared with control group（ P〈0.05）.And the levels of the expression were the lowest in the combined group and the highest in＆amp;nbsp;control group.HIF -1αis positively correlated with b -FGF （ P〈0.05 ） , b -FGF is positively correlated with VASH-1 （ P〈0.05 ） , HIF-1αis uncorrelated with VASH-1.Conclusion Tetramethylpyrazine combined with cisplatin decreased the expression of HIF-1α, thereby reducing the expression of b-FGF and VASH-1 , inhibiting the tumor growth synergistically.