摘要
目的观察益气温阳颗粒联合贝伐珠单抗对Lewis荷瘤小鼠肿瘤血管内皮生长因子(vascular endothelial growth factor,VEGF)、血管内皮生长因子受体2(vascular endothelial growth factor receptor 2,VEGFR-2)表达,以及肿瘤微血管密度(microvessel density,MVD)的影响,探究益气温阳颗粒联合贝伐珠单抗可能存在的抗肿瘤血管机制。方法将40只C57BL/6J小鼠造模后随机分为模型组、西药组、中药组、联合用药组,每组10只,分别予生理盐水0.4 mL(1次/天)、贝伐珠单抗15 mg/kg腹腔注射(2次/周)、益气温阳颗粒生药20 g/kg(1次/天)、贝伐珠单抗15 mg/kg腹腔注射(2次/周)联合益气温阳颗粒生药20 g/kg(1次/天)、生理盐水0.4 mL(1次/天),2周后处死。计算抑瘤率,RT-PCR法检测VEGF mRNA转录水平,免疫组化染色法检测肿瘤组织VEGFR-2,检测反映MVD的血小板—内皮细胞粘附分子-1(platelet endothelial cell adhesion molecule-1,CD31)的表达。结果中药组、西药组、联合用药组的抑瘤率分别为9.89%、11.76%、26.97%;与模型组相比,治疗组均可显著降低肿瘤组织VEGF mRNA转录水平(P<0.01);联合用药组可降低肿瘤组织VEGFR-2、CD31、MVD表达(P<0.01),而中药组和西药组均有下降趋势,但无统计学意义(P>0.05)。结论益气温阳颗粒联合贝伐珠单抗可能通过调控VEGF/VEGFR-2血管生成通路,减少肿瘤新血管生成,降低肿瘤组织MVD,在一定程度上抑制肿瘤生长。
Objective To research the anti-angiogenesis effect of Yiqi Wenyang granules(YQWYG)combined with bevacizumab on tumor and the mechanism of its anti-angiogenesis by observing the changes of the expression of vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor 2(VEGFR-2)and tumor microvessel density(MVD)in Lewis tumor-bearing mice.Methods Forty male C57BL/6J mice were randomly divided into 4 groups,the namely the model group(MG),the western medicine group(WMG),the TCM group(TCMG)and the integrative medicine group of TCM and western medicine(IMGTW).0.4 mL saline was adopted to the NG and MG once a day by gavage.Intraperitoneal injection of bevacizumab with 15 mg/kg was adopted to the WMG twice a week.Gavage of QYWYG with 20 g/kg was adopted to TCMG once a day.Gavage of QYWYG with 20 g/kg and intraperitoneal injection of bevacizumab with 15 mg/kg were simultaneously adopted to IMGTW twice a week.All the mice were killed and the tumors were removed to calculate the inhibition effects after two weeks.The method of quantitative polymerase chain reaction(q-PCR)was used to detect the gene expressions of vascular endothelial growth factor(VEGF mRNA).Immunohistochemical staining was used to detect the expressions of CD31 and VEGFR-2 in tumor tissues.Results The tumor inhibition rates in the TCMG,the WMG,and the IMGTW were 9.89%,11.76%,and 26.97%.Compared with the model group,the treatment group could reduce the expression of the expression of VEGF mRNA in tumors(P<0.01).The IMGTW has better effect in decreasing the expression of CD31 and VEGFR-2 with statistical significance(P<0.05),while there is a downward trend in the TCMG and the WMG(P>0.05).Conclusion YQWYG combined with bevacizumab may decrease the expression of the expressions of VEGF,VEGFR-2 and MVD(CD31),which finally inhibited angiogenesis and induced apoptosis in tumor.
作者
刘伟
梁绵杰
姜可园
谢莉莹
王雪玭
张笑雪
LIU Wei;LIANG Mianjie;JIANG Keyuan;XIE Liying;WANG Xuepin;ZHANG Xiaoxue(Department of Respiratory and Critical Care,The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China)
出处
《环球中医药》
CAS
2022年第7期1151-1157,共7页
Global Traditional Chinese Medicine
基金
国家自然科学基金(81603447)
天津市高等学校创新团队培养计划(TD13-5051)
第二批天津市中医药专家学术经验继承项目(津卫中[2018]176号)
天津市卫生与健康委员会“十二五”特色学科:中医内科学(20200402)。
