基于PPARγ靶点的染料木黄酮对骨肉瘤裸鼠新生血管生成及巨噬细胞极化的影响  

Effect of Genistein Based on PPARγTarget on Angiogenesis and Macrophage Polarization in Nude Mice with Osteosarcoma

作　　者：刘焕茹 李险峰[2] 张翼[3] 朱伦庆[4] LIU Huanru;LI Xianfeng;ZHANG Yi;ZHU Lunqing(College of Basic Medical,Shanxi Medical University,Taiyuan Shanxi 030000,China;Department of Oncology and Radiotherapy,First Hospital of Shanxi Medical University,Taiyuan Shanxi 030001,China;Department of Orthopedics,The First Affiliated Hospital of Zhengzhou University,Zhengzhou Henan 450052,China;Department of Orthopedics,Children’s Hospital of Soochow University,Suzhou Jiangsu 215003,China)

机构地区：[1]山西医科大学基础医学院,山西太原030000 [2]山西医科大学第一医院肿瘤放疗科,山西太原030001 [3]郑州大学第一附属医院骨科,河南郑州450052 [4]苏州大学附属儿童医院骨科,江苏苏州215003

出　　处：《中国医疗设备》2024年第11期137-142,164,共7页China Medical Devices

基　　金：国家自然科学基金(81473268;81402475)。

摘　　要：目的探讨基于过氧化物酶体增殖物激活受体(Peroxisome Proliferators-Activated Receptorγ,PPARγ)靶点的染料木黄酮对骨肉瘤裸鼠新生血管生成及巨噬细胞极化的影响。方法选取35只裸鼠建立骨肉瘤裸鼠模型,建模成功后按照随机数字方法分为模型组、低剂量染料木黄酮组、中剂量染料木黄酮组、高剂量染料木黄酮组及顺铂组,每组6只。低、中、高剂量染料木黄酮组分别灌胃50、100及200 mg/kg的染料木黄酮,顺铂组腹腔注射2 mL/kg的顺铂注射液,模型组灌胃等体积的0.9%NaCl溶液。电子天平称量肿瘤质量并计算肿瘤抑制率;HE染色观察肿瘤组织病理形态;免疫组化检测血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)肿瘤微血管密度(Microvessel Density,MVD);免疫印记检测一氧化氮合酶(Inducible Nitric Oxide Synthase,iNOS)、重组分化簇163(Recombinant Cluster of Differentiation 163,CD163)及PPARγ、兔抗人蛋白激酶B(Protein Kinase B,AKT)、糖原合成酶激酶-3β(Glycogen Synthase Kinase 3β,GSK-3β)蛋白。结果与模型组相比,低、中、高剂量染料木黄酮组及顺铂组瘤体质量降低,抑瘤率升高(P<0.05);高剂量染料木黄酮组与顺铂组比较差异无统计学意义(P>0.05)。模型组、低、中、高剂量染料木黄酮组及顺铂组VEGFA-MVD数目分别为(17.25±2.05)、(14.10±1.72)、(13.56±1.67)、(6.35±0.52)及(6.14±0.47)个,差异有统计学意义(F=71.340,P<0.05)。与模型组相比,低、中、高剂量染料木黄酮组及顺铂组iNOS及PPARγ蛋白升高,CD163、AKT、GSK-3β蛋白降低(P<0.05);高剂量染料木黄酮组与顺铂组比较差异无统计学意义(P>0.05)。结论染料木黄酮可抑制骨肉瘤裸鼠瘤体生长,并减少M1型巨噬细胞向M2型转化,发挥抗肿瘤作用,作用机制可能与上调PPARγ表达相关。Objective To investigate the effect of genistein based on peroxisome proliferators-activated receptorγ(PPARγ)target on angiogenesis and macrophage polarization in nude mice with osteosarcoma.Methods A total of 35 nude mice were selected to establish the osteosarcoma nude mouse model.After successful modeling,the nude mice were randomly divided into model group,low-dose genistein group,medium-dose genistein group,high-dose genistein group and cisplatin group,with 6 mice in each group.The low,medium,and high-dose genistein groups were orally gavaged with 50,100,and 200 mg/kg of genistein,respectively;the cisplatin group received intraperitoneal injection of 2 mL/kg cisplatin solution;the model group was gavaged with an equivalent volume of 0.9%NaCl solution.The tumor mass was weighed using an electronic balance and the tumor inhibition rate was calculated;HE staining was used to observe the pathological morphology of tumor tissue;immunohistochemistry was performed to detect vascular endothelial growth factor A(VEGFA)expression and tumor microvessel density(MVD);immunostaining was used to detect inducible nitric oxide synthase(iNOS),recombinant cluster of differentiation 163(CD163),PPARγ,rabbit anti-human protein kinase B(AKT),and glycogen synthase kinase 3β(GSK-3β)proteins.Results Compared with the model group,the tumor weight of low,medium and high dose genistein groups and cisplatin groups were decreased and the tumor inhibitory rate was increased(P<0.05);there were no differences between high dose genistein group and cisplatin group(P>0.05).The number of VEGFA-MVD in model group,low,medium and high dose genistein group and cisplatin group were(17.25±2.05),(14.10±1.72),(13.56±1.67),(6.35±0.52)and(6.14±0.47),respectively,with statistically significant difference(F=71.340,P<0.05).Compared with model group,iNOS and PPARγproteins were increased in low,medium and high dose genistein groups and cisplatin groups,while proteins of CD163,AKT and GSK-3βwere decreased(P<0.05);there were no statistically signific

关 键 词：骨肉瘤 染料木黄酮 血管生成 巨噬细胞极化 过氧化物酶体增殖物激活受体 

分 类 号：R738[医药卫生—肿瘤]