蝎毒多肽提取物对化疗期间再增殖H22肿瘤组织HIF-1α和SDF-1/CXCR4表达的影响  

Effect of polypetide extract from scorpion venom (PESV) on expression of HIF-1α and SDF-1/CXCR4 in repopulating H22 tumour tissue during chemotherapy treatment

作　　者：王兆朋[1] 张维东[1] 武利存[1] 贾青[1] 王朝霞[1] 张月英[1] 宁云娜[1] 

机构地区：[1]山东省医学科学院基础医学研究所山东省现代医用药物与技术重点实验室,山东济南250062

出　　处：《中国中药杂志》2011年第13期1803-1807,共5页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(30873408);山东省自然科学基金项目(ZR2010HQ003);山东省科技攻关基金项目(2008GG30002067)

摘　　要：目的:研究化疗期间再增殖中H22肿瘤组织HIF-1α和SDF-1/CXCR4表达的变化及蝎毒多肽提取物(polypep-tide extract from scorpion venom,PESV)对其表达的影响,以探讨肿瘤组织再增殖期间新生血管生成发生的机制。方法:以免疫组织化学方法检测化疗期间不同时间点肿瘤组织HIF-1α,SDF-1及CXCR4的表达,以ELISA方法检测肿瘤组织SDF-1的含量,以Qwin V3图像分析软件对肿瘤组织HIF-1α,SDF-1及CXCR4表达进行分析,并进行相关性分析。结果:模型组肿瘤组织HIF-1α表达在第14天和第21天无差异性,在第28天表达水平显著升高;PESV低剂量组在3个时间点表达无差异性,而PESV高剂量组表达在第21天最低,在第14天最高,ELSA检测结果显示,荷瘤对照组表达逐渐增多,尤其是在第14～21天,增加迅速。模型组,SDF-1表达在14～21 d表达增加缓慢,但在21～28 d增加迅速;PESV高、低剂量组SDF-1表达水平增加缓慢,尤其是高剂量组,3个时间点肿瘤组织表达水平差异无显著性。免疫组织化学检测SDF-1结果和ELISA一致。对HIF-1α和SDF-1灰度值分析结果显示,r=0.805,两者存在相关性。PESV低、高剂量组肿瘤组织CXCR4下调,但PESV低、高剂量组之间无差异性。结论:在化疗期间肿瘤组织产生HIF-1α,HIF-1α诱导间质组织分泌SDF-1,HIF-1α和SDF-1促进VEGF的表达上调,从而诱发肿瘤内新生血管的生成。PESV有效抑制HIF-1α和SDF-1的表达。Objective： To study the expression of HIF-1α and SDF-1/CXCR4 in repopulating H22 tumor tissue and the mechanism of angiogenesis of polypeptide extract from scorpion venom（PESV） during chemotherapy treatment.Method： The expression of HIF-1α and SDF-1/CXCR4 in H22 tumor tissue was monitored by immunohistochemistry,and the expression level was determined by Qwin V3 image analyzing software.The correlation between HIF-1α and SDF-1 was analyzed.SDF-1 content was detected by ELISA.Result： HIF-1α expression was found no difference in model group between 14 d and 21 d,and up-regulated in 28 d.There was no change of HIF-1α expression was observed in low-dose PESV group.In high-dose PESV group,the level of HIF-1α expression was high in 14 d and low in 21 d.ELISA detecting showed SDF-1 content increased slowly from 14 d to 21 d,highly from 21 d to 28 d.But in high-dose PESV groups,the content increased slowly all the time.The immunohitochemistry method got the same result with ELISA.Correlation analysis showed r=0.805.CXCR4 expression down-regulated in two PESV treated groups,and no difference was found between these two groups.Conclusion： HIF-1α and SDF-1 participated in VEGF expression and angiogenesis in tumor tissue during chemotherapy,while PESV could inhibit the expression of HIF-1α and SDF-1.

关 键 词：蝎毒多肽提取物 缺氧诱导因子-1α 基质衍生因子-1 CXC趋化因子受体4 再增殖 化疗 

分 类 号：R965[医药卫生—药理学]