CAJ | 학술논문

目的：研究川芎嗪联合顺铂对Lewis肺腺癌小鼠中含凝血酶敏感素1型基序的解聚素样金属蛋白酶（ADAMTS1）和血管内皮生长因子（VEGF）表达的影响。方法健康雄性C57BL／6小鼠接种Lewis肺腺癌细胞，复制lewis肺癌小鼠移植瘤模型。模型小鼠随机分为4组，模型组（0.9％氯化钠，0.2 mL），川芎嗪组（100 mg· kg－1，0.2 mL），顺铂组（2 mg· kg－1，0.2 mL），联合组（如上述同等剂量，0.2 mL），每组14只，连续用药14 d。于给药结束后5 d，脱颈处死全部小鼠，剥离皮下肿瘤，称取瘤体重和测量体积，免疫组织化学方法检测VEGF和ADAMTS1蛋白的表达。结果各用药组肿瘤的生长受到明显的抑制，瘤体重明显低于模型组（P＜0.05），联合组抑瘤率明显高于其他3个组（P＜0.05）。与模型组比较，在各用药组的肿瘤组织中， ADAMTS1蛋白的表达均显著增加（P＜0.05），而VEGF蛋白的表达均显著降低（P＜0.05），且ADAMTS1与VEGF的表达呈负相关（P＜0.05）。结论川芎嗪能够明显抑制Lewis肺腺癌移植瘤的生长，与顺铂具有协同作用，其机制可能通过上调ADAMTS1、下调VEGF的表达来达到抗肿瘤血管生成的作用。
목적：연구천궁진연합순박대Lewis폐선암소서중함응혈매민감소1형기서적해취소양금속단백매（ADAMTS1）화혈관내피생장인자（VEGF）표체적영향。방법건강웅성C57BL／6소서접충Lewis폐선암세포，복제lewis폐암소서이식류모형。모형소서수궤분위4조，모형조（0.9％록화납，0.2 mL），천궁진조（100 mg· kg－1，0.2 mL），순박조（2 mg· kg－1，0.2 mL），연합조（여상술동등제량，0.2 mL），매조14지，련속용약14 d。우급약결속후5 d，탈경처사전부소서，박리피하종류，칭취류체중화측량체적，면역조직화학방법검측VEGF화ADAMTS1단백적표체。결과각용약조종류적생장수도명현적억제，류체중명현저우모형조（P＜0.05），연합조억류솔명현고우기타3개조（P＜0.05）。여모형조비교，재각용약조적종류조직중， ADAMTS1단백적표체균현저증가（P＜0.05），이VEGF단백적표체균현저강저（P＜0.05），차ADAMTS1여VEGF적표체정부상관（P＜0.05）。결론천궁진능구명현억제Lewis폐선암이식류적생장，여순박구유협동작용，기궤제가능통과상조ADAMTS1、하조VEGF적표체래체도항종류혈관생성적작용。
Objective To investigate the effect of Tetramethylpyrazin ( TMP) combined with cisplatin( DDP) on expression of a disintegrin and metalloproteinase with thrombospondin typeⅠmotif ( ADAMTS1 ) and vascular endothelial growth factor ( VEGF ) of Lewis lung cancer rats.Methods The Lewis lung carcinoma model of c57 bl/6 were produced by intraperitoneal injection of Lewis lung cancer cells in right axillary, per 0.2 mL.Then the 56 tumor-bearing mice were randomized into 4 groups: model group ( 0.9%NaCl, 0.2 mL ) , TMP group ( 100 mg· kg-1, 0.2 mL),DDP group(2 mg· kg -1, 0.2 mL),TMP+DDP group( doses as above, n=14).Different administration were served from day 5 transplantation and all mice were sacrificed after 19 days.The weight and volume of transplanted tumors were recorded.And the expressions of VEGF and ADAMTS1 were detected by immunhistochem-isty.Results Compared with model group, the growth of transplanted tumors in TMP group, DDP group, TMP+DDP group were significantly inhibited.The weight of tumor body in the three groups were markedly lower than that of model group.The inhibitory effect of TMP combined with DDP on tumor growth was enhanced com-pared with TMP or DDP alone treatment.The expression levels of VEGF were significantly lower but ADAMTS1 was sig-nificantly higher in TMP group,DDP group,TMP+DDP group than that in model group ( P<0.05 ).Pearson correla-ted analysis showed that the expression VEGE and ADAMTS1 negatively correlated(P<0.05).Conclusion TMP has synergetic inhibitory effect with DDP on transplanted tumor growth of Lewis lung carcinoma in mice.The action mecha-nism may be due to down-regulate the VEGF expression and up-regulate the ADAMTS1 expression,inhibiting tumor angiogenesis.