兔肝VX2瘤化疗栓塞介入术前后MR扩散加权成像表现和增殖、转移基因表达相关性的动态研究

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目的探讨兔肝 VX_2瘤化疗栓塞介入术前后增殖细胞抗原(PCNA)、凋亡活化基因(Bax)、转移抑制基因23(nm23)、上皮型钙依赖黏连蛋白(E-cad)表达与扩散加权成像(DWI)表观扩散系数(ADC)值间的关系。方法 40个兔肝 VX_2瘤模型,分为对照组与介入术后16、32、48 h 组,每组10个模型。4组分别在化疗栓塞介入术前与化疗栓塞介入术后16、32、48 h 行 DWI,并对各组肿瘤标本行病理及免疫组织化学检查。对上述不同时间及不同部位(肿瘤周围正常肝组织、肿瘤外周部分组织、肿瘤周围部分组织、肿瘤中央部分组织)之间 PCNA、Bax、nm23、E-cad 表达指数以及表达指数与相应部位 ADC 值的关系进行分析。结果(1)对照组 VX_2瘤外周部分、周围部分与中央部分组织PCNA 表达指数(分别为65.1%、74.7%、59.0%)明显高于周围正常肝实质(8.3%)(χ~2=19.08,P<0.01);上述部位的 nm23(分别为1.7%、0.4%、6.2%)、Bax(分别为2.0%、1.2%、2.2%)及 E-cad(分别为6.2%、2.0%、1.6%)表达指数明显低于周围正常肝实质(分别为16.5%、40.0%、78.0%)(χ~2值分别为12.6、20.17、22.20,P 值均<0.01)。(2)介入术后16、32、48 h 组 VX_2瘤周围部分组织 PCNA 表达指数分别为83.0%、92.6%、85.7%,nm23表达指数分别为2.3%、7.4%、4.2%,Bax 表达指数分别为0.8%、0.5%、0.9%,E-cad 表达指数分别为2.8%、1.0%、1.1%,与对照组上述指标比较,PCNA、nm23表达指数先增加后下降(χ~2值分别为14.37、8.94,p 值<0.05),Bax、E-cad 表达指数差异无统计学意义(χ~2值分别为1.98、3.88,P 值>0.05)。(3)b=100 s/mm~2时,对照组与介入术后16、32、48 h 组肿瘤周围部分 ADC 值分别为(1.71±0.27)×10~(-3)、(1.24±0.22)×10~(-3)、(1.48±0.37)×10~(-3)及(1.57±0.23)×10~(-3)mm~2/s,PCNA 的表达指数与肿瘤周围部分组织 ADC 值之间存在相关关系(r=-0.68,P=0.000);nm23、Bax、E-cad 的表达指数与 ADC 值之间不存在相关关系(r 值分别为-0.20、0.17、-0.10,P 值均>0.05)。结论化疗栓塞介入术后 VX_2瘤浸润、转移潜能下降,但短期内将导致肿瘤增殖能力的加强。ADC 值的变化,一定程度上可以反映肿瘤细胞的增殖情况。 Objective To investigate the expression and proliferation of proliferating cell antigen (PCNA), apoptosis-activating gene (Bax), metastasis suppressor gene 23 (nm23) and E-cadherin before and after interventional chemotherapy with VX_2 in rabbits Relationship Between Apparent Diffusion Coefficients (ADC) of Weighted Imaging (DWI). Methods Forty rabbits liver VX 2 tumor models were divided into control group and 16, 32 and 48 h groups after intervention, with 10 models in each group. Four groups received DWI at 16, 32, and 48 h after chemoembolization and chemoembolization respectively. Pathological and immunohistochemical examination was performed on the tumor samples in each group. The expressions of PCNA, Bax, nm23 and E-cad, the expression index and ADC value of the corresponding sites at different time and different sites (normal liver tissue, peripheral tumor tissue, tumor surrounding tissue and central tumor tissue) The relationship between the analysis. Results (1) PCNA expression index in the peripheral and central part of VX_2 tumor was 65.1%, 74.7% and 59.0% respectively in the control group, which was significantly higher than that in the surrounding normal liver parenchyma (8.3%) (χ ~ 2 = 19.08, (6.2%, 2.0%, 1.6%, respectively) in the above sites were nm23 (1.7%, 0.4%, 6.2% ) Expression index was significantly lower than the surrounding normal liver parenchyma (16.5%, 40.0%, 78.0%, respectively) (χ ~ 2 values ​​were 12.6,20.17,22.20, P values ​​were <0.01). (2) PCNA expression index of VX2 surrounding tissues was 83.0%, 92.6% and 85.7% respectively at 16, 32 and 48 h after intervention, and the expression of nm23 was 2.3%, 7.4% and 4.2% (0.8%, 0.5%, 0.9%). The expression of E-cad was 2.8%, 1.0% and 1.1% respectively. Compared with the control group, the expression of PCNA and nm23 firstly increased and then decreased (χ ~ 2 = 14.37 , 8.94, p <0.05). The expression of Bax and E-cad had no statistical significance (χ ~ 2 = 1.98,3.88, P> 0.05). (3) When b = 100 s / mm ~ 2, the ADC values ​​of the peripheral part of the tumor in the control group and the 16, 32 and 48 h after intervention were (1.71 ± 0.27) × 10 -3 and 1.24 ± 0.22 ) Were significantly higher than those in the control group (P <0.05). The expression of PCNA was significantly correlated with the expression of ADC (R = -0.68, P = 0.000). There was no correlation between the expressions of nm23, Bax and E-cad and the ADC value (r values ​​were -0.20, 0.17, -0.10, P Value> 0.05). Conclusion VX2 tumor invasion and metastasis potential decrease after chemotherapy and embolization, but in a short term, it leads to the enhancement of tumor proliferation. ADC value changes, to some extent, can reflect the proliferation of tumor cells.
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