摘要
目的对血浆指标及动态对比增强超声(DCE-US)检查肝癌血管正常化时间窗的诊断价值进行分析。方法将60只7~8周龄造模成功的雄性SD大鼠,随机分为实验组(n=30)及对照组(n=30),实验组予索拉菲尼80 mg/kg静脉注射,对照组注射磷酸盐缓冲液(PBS),分别在治疗第0天(用药前一天)、2天、4天、6天及第8天行DCE-US检查。在设定时间点,取大鼠眶后静脉血,应用iTRAQ技术分析血浆中相关成分的变化,利用GEO在线分析工具对差异表达蛋白进行分析;并取大鼠肿瘤血管组织,对其血管正常化指标进行检测,比较两组大鼠上述指标,并对DCE-US及血浆蛋白指标与血管正常化指标的相关性进行分析。结果经索拉菲尼干预后实验组大鼠血管渗透性、血流灌注指数(PI)及峰值时间(TTP)水平下降,α-SMA^(+)/CD31^(+)周细胞覆盖率及MTT水平升高,与对照组比较差异有统计学意义(均P<0.05);而对照组干预前后上述指标无明显变化(均P>0.05)。血浆蛋白组学共筛选出差异蛋白表达12个,其中上调蛋白5个,下调蛋白7个,且差异表达蛋白间形成相互作用关系网,以对氧磷酶(PON1)、淀粉样蛋白A(SAA2)、富组氨酸蛋白(HRG)等蛋白为主要差异蛋白。相关性分析示血管渗透性与PI、TTP、HRG、血红蛋白α-2(HBA2)、血红蛋白β亚基(HBB)、补体C2(C2)呈显著正相关(均P<0.05),与SAA2、载脂蛋白C-Ⅲ(APOC3)、载脂蛋白C-Ⅳ(APOC4)、丛生蛋白(CLU)、PON1、铜蓝蛋白(CP)及B重组蛋白(CFP)呈显著负相关(均P<0.05);α-SMA^(+)/CD31^(+)周细胞覆盖率与SAA2、APOC3、APOC4、CLU、PON1、CP及CFP呈正相关(均P<0.05),与PI、TTP、HRG、HBA2、HBB、C2及补体抗体4A(C4A)呈显著负相关(均P<0.05)。结论PI、TTP、SAA2、APOC3等DCE-US检查及血浆蛋白指标与肝癌血管正常化指标间存在显著相关性,可反映肿瘤血管正常化程度,有助于指导临床治疗。
Objective The diagnostic value of plasma index and DCE-US in detecting the time window of liver cancer vessel normalization was analyzed.Methods 60 male SD rats aged 7 to 8 weeks were randomly divided into experimental group(n=30)and control group(n=30).The experimental group was given intravenous injection of 80 mg/kg sorafenib,and the control group was injected with phosphate buffer(PBS).DCE-US examination was performed on day 0(one day before medication),day 2,day 4,day 6 and day 8,respectively.At the set time point,the retroorbital venous blood of the rats were collected;the changes of relevant components in plasma were analyzed by iTRAQ technique;and the differentially expressed proteins were analyzed by GEO online analysis tool.The tumor vascular tissues of the rats were taken and the vascular normalization indexes were detected.The above indexes were compared between the two groups of the rats,and the correlation between DCE-US and plasma protein indexes and vascular normalization indexes were analyzed.Results After the intervention of Sorafenib,the levels of vascular permeability,blood perfusion index(PI)and peak time(TTP)of the experimental group were decreased,and the cell coverage and MTT level ofα-SMA^(+)/CD31^(+)weeks were increased,with statistical significance compared with the control group(all P<0.05).There were no significant changes in the above indexes in the control group before and after the intervention(all P>0.05).A total of 12 differentially expressed proteins were detected by plasma proteomics,including 5 up-regulated proteins and 7 down-regulated proteins,and a network of interactions were formed among differentially expressed proteins,with paraoxonase(PON1),amyloid A(SAA2),histidine rich protein(HRG)and other proteins as the main differentially expressed proteins.Correlation analysis showed that vascular permeability was significantly positively correlated with PI,TTP,HRG,hemoglobinα-2(HBA2),hemoglobinβsubunit(HBB)and complement C2(C2)(all P<0.05).It was significantly negatively cor
作者
徐蓉
马楠
宋巍
XU Rong;MA Nan;SONG Wei(Department of Oncology,People′s Hospital of Xinjiang Uyghur Autonomous Region,Urumqi 830000,China;Department of Breast Thyroid,People′s Hospital of Xinjiang Uyghur Autonomous Region,Urumqi 830000,China;Department of Hepatobiliary Surgery,People′s Hospital of Xinjiang Uyghur Autonomous Region,Urumqi 830000,China)
出处
《新疆医科大学学报》
CAS
2023年第1期37-42,共6页
Journal of Xinjiang Medical University
基金
新疆维吾尔自治区自然科学基金(2020D01C094)。
关键词
DCE-US
肝癌
血管正常化
蛋白表达差异
DCE-US
liver cancer
vascular normalization
protein expression difference
