川芎嗪联合顺铂对肺癌中血管内皮生长因子和肿瘤抑素表达的影响

Effect of tetramethylpyrazine combined with cisplatin on expression of cascular endothelial growth factor and tumstatin of Lewis lung carcinoma in mice

目的探讨川芎嗪联合顺铂对Lewis肺癌的抑制作用及机制。方法建立小鼠移植瘤模型,随机分为4组:空白组(0.9%氯化钠,0.2 m L)、顺铂组(2mg·kg-1,0.2 m L)、川芎嗪组(100 mg·kg-1,0.2 m L)、联合组(川芎嗪联合顺铂,剂量同上,0.2 m L),10只/组,连续给药14 d;计算肿瘤重量及抑瘤率;电镜观察肿瘤细胞及血管结构;用免疫组化和蛋白印迹法检测血管内皮生长因子(VEGF)、肿瘤抑素表达情况。结果空白组,肿瘤生长最快,联合组最慢。联合组,抑瘤率(59.81%)明显高于其他3组。联合组,VEGF的表达显著低于其他3组(P<0.01),肿瘤抑素表达显著高于其他3组(P<0.01)。VEGF与肿瘤抑素的表达呈负相关性(P<0.05)。结论川芎嗪可抑制肺癌生长,与顺铂联用有协同作用;其作用机制可能与抑制VEGF、促进肿瘤抑素表达有关。

Objective To explore the inhibitiory effect and mechanism of tetramethylpyrazine in combination with cisplatin on Lewis lung carci-noma rats.Methods A transplanted tumor model of Lewis lung carcino-ma was establised.Then randomly divided into 4 groups： control group （0.9%NaCl,0.2 mL）,cisplatin group （2 mg· kg -1,0.2 mL）,tetram-ethylpyrazine group （100 mg· kg -1,0.2 mL）, and combination group （ the doses as above ） , each 10 rats .Different treatments were served for 14 days,then all of rats were put to death.The tumor weight and in-hibitory rate were calculated .The tumor cells and vascular structure were observed under electron microscope .The expression of cascular endothe-lial growth factor（VEGF） and tumstatin were decteted by immunohisto-chemistry and Western blot .Results The weight was increased in all the groups.The control group was obviously fast than the other group . The combination group was obviously the slowest .The inhibition rate in combination group was significantly higher than the other groups .The tumstatin expression of combination group was obviously lower than the other three groups.The VEGF expression of combination group were sig-nificantly lower than the other three groups .The expression of VEGF had negative correlation with tumstatin （ P 〈0.05 ） .Conclusion Tetrame-thylpyrazine can effectively inhibit the growth of Lewis lung cancer trans-planted tumor , and has synergetic effect when combined with cisplatin .The mechanism might be that it can inhibit tumor angiogenesis by reducing VEGF expression , and promoting tumstatin expression.