低频低功率聚焦超声辐照造影剂微泡空化效应联合贝伐珠单抗治疗兔VX2肝癌的实验研究  

Experimental study of low frequency and low power focused ultrasound irradiation microbubbles cavitation effect combined with bevacizumab in the treatment of rabbits VX2 liver cancer

作　　者：王子龙[1] 张容亮 李进涛 马艺斐 陆永萍 WANG Zilong;ZHANG Rongliang;LI Jintao;MA Yifei;LU Yongping(Department of Ultrasonography,Affiliated Hospital of Yunnan University,Kunming,Yunnan 650021,China;Department of Experimental Zoology,Kunming Medical University,Kunming,Yunnan 650500,China)

机构地区：[1]云南大学附属医院超声科,昆明650021 [2]昆明医科大学实验动物学部,650500

出　　处：《重庆医学》2023年第7期970-975,共6页Chongqing medicine

基　　金：云南省高等学校工程研究中心建设项目(2021);云南省科技厅-昆明医科大学联合基金项目(202101AY070001-279);云南省科技厅-昆明医科大学联合专项资金项目[2019FE001(-093)]。

摘　　要：目的探讨超声辐照造影剂微泡空化效应联合贝伐珠单抗治疗兔VX2肝癌的效果。方法选取VX2肝癌模型兔30只,分为3组,每组10只:超声辐照+贝伐珠单抗+造影剂微泡组(U+B+M组)、贝伐珠单抗组(B组)、对照组(C组);U+B+M组、B组每7天治疗1次,共治疗4次。分别于治疗前和治疗第28天行二维超声测量肿瘤体积并计算肿瘤体积增长率,通过超声造影计算肿瘤峰强度变化情况;ELISA方法检测兔血清中的血管内皮生长因子(VEGF)水平。苏木素-伊红(HE)染色观察肿瘤病理切片,通过免疫组织化学染色计数肿瘤的微血管密度(MVD),分析MVD与VEGF的相关性。结果治疗后,U+B+M组肿瘤体积增长率最低,其次是B组,3组间比较差异有统计学意义(P<0.05)。超声造影峰强度与血清VEGF水平变化具有一致性:治疗前各组超声造影峰强度、VEGF水平比较差异无统计学意义(P>0.05);治疗后,U+B+M组及B组超声造影峰强度、VEGF水平与治疗前比较降低,差异均有统计学意义(P<0.05),且U+B+M组减低程度明显大于B组(P<0.05);C组治疗前、后超声造影峰强度比较差异无统计学意义(P>0.05),VEGF水平差异有统计学意义(P<0.05);治疗后,3组超声造影峰强度、VEGF水平比较差异有统计学意义(P<0.05),进一步组间两两比较差异也有统计学意义(P<0.05)。病理HE染色可见U+B+M组、B组部分肿瘤微血管囊状扩张,管壁不连续,少许红细胞渗出至管腔外,且U+B+M组较B组明显;肿瘤组织中MVD与血清VEGF水平呈显著正相关(r=0.94,P<0.01)。结论低频低功率聚焦超声及其造影剂微泡产生的空化效应能一定程度上增强贝伐珠单抗对兔VX2肝癌的治疗效果。Objective To investigate the effect of ultrasound irradiation microbubbles cavitation combined with bevacizumab in the treatment of VX2 liver cancer in rabbits.Methods Thirty VX2 liver cancer model rabbits were divided into three groups:the ultrasound irradiation+bevacizumab+contrast agent microbubble group(the U+B+M group),the bevacizumab group(the B group),and the control group(the C group),10 rabbits in every group.The U+B+M group and the B group were treated once every 7 days,a total of 4 times.Before and on the 28th day of treatment,the tumor volume was measured and the growth rate of tumor volume was calculated by two-dimensional ultrasound,the changes of tumor peak intensity were calculated by contrast-enhanced ultrasound.The level of vascular endothelial growth factor(VEGF)in rabbit serum was detected by ELISA.Hematoxylin-eosin(HE)staining was used to observe the pathological sections of tumor,and the microvessel density(MVD)of tumor was counted by immunohistochemical staining,and the correlation between MVD and VEGF was analyzed.Results The growth rate of tumor volume in the U+B+M group was the lowest,followed by group B,there were statistically significant differences among the three groups(P<0.05).The peak intensity of contrast-enhanced ultrasound was consistent with the change of serum VEGF level:there was no significant difference in peak intensity of contrast-enhanced ultrasound and VEGF level among the three groups before treatment(P>0.05);After 28 days of treatment,the peak intensity of contrast-enhanced ultrasound and the level of VEGF in the U+B+M group and the B group were significantly lower than those before treatment(P<0.05),and the reduction degree of the U+B+M group was significantly greater than that of the B group(P<0.05).There was no significant difference in peak intensity of contrast-enhanced ultrasound before and after treatment in the C group(P>0.05),but there was significant difference in VEGF level(P<0.05).After 28 days of treatment,the peak intensity of contrast-enhanced ultrasou

关 键 词：低频低功率超声 微泡 空化效应 贝伐珠单抗 VX2肝癌 

分 类 号：R445.1[医药卫生—影像医学与核医学]