表观扩散系数与缺氧诱导因子-1α、核因子-κB在布加综合征大鼠模型中的相关性初探

Preliminary study on the correlation between apparent diffusion coefficient, hypoxia-inducible factor-1α and nuclear factor-κB in Budd-Chiari syndrome rat model

目的探讨表观扩散系数(apparent diffusion coefficient,ADC)、缺氧诱导因子-1α(hypoxiainducible factor-1α,HIF-1α)、核因子-κB(nuclear factor-κB,NF-κB)在布加综合征(Budd-Chiari syndrome,BCS)大鼠模型中的相关性。方法结扎大鼠肝后段下腔静脉建立BCS动物模型,实验分正常组(n=15)、模型组(n=60)和假手术组(n=60),模型组和假手术组分术后1、4、8、12周4个亚组,各亚组15只。观察各组肝脏ADC值的变化。行HE染色观察各组肝组织变化,免疫组化检测各组大鼠肝组织中HIF-1α、NF-κB的表达。结果正常组及假手术组的DSA均无阳性表现,模型组肝后段IVC管腔变窄,远端扩张,并见侧支循环。正常组及假手术组的HE染色及免疫组化均无阳性表现,模型组随着梗阻时间延长,肝脏病理损伤逐渐加重。术后1、4、8、12周模型组ADC值[(1.23±0.08)、(1.03±0.09)、(1.12±0.09)、(1.18±0.07)]均低于正常组及假手术组(均P<0.05);模型组ADC值先下降后升高,第4周最低。术后1、4、8、12周模型组HIF-1α、NF-κB的mRNA及蛋白表达均高于正常组及假手术组(均P<0.05);模型组HIF-1α、NF-κB先升高后下降,术后第4周达到最高。模型组HIF-1α与NF-κB呈正相关(r=0.960,P=0.001);ADC值均与HIF-1α(r=-0.718,P=0.001)、NF-κB(r=-0.699,P=0.001)呈负相关。结论BCS肝脏ADC值与HIF-1α、NF-κB存在一定相关性,并与淤血缺氧程度密切相关,可作为无创评估BCS肝损伤的一个新的选择。

Objective To investigate the correlation between apparent diffusion coefficient(ADC),hypoxiainducible factor-1ɑ(HIF-1α)and nuclear factor-κB(NF-κB)in rat model of Budd-Chiari syndrome(BCS).Methods BCS model was established by partial ligation of the inferior vena cava of rat.The animals were divided into normal group(15 rats),model group(subgroup at 1,4,8,and 12 week,15 rats each)and sham group(subgroup at 1,4,8,and 12 week,15 rats each).The changes of ADC of liver were observed by MRI.Changes of liver tissue in each group were observed by HE staining,and the expressions of HIF-1αand NF-κB in liver tissue of each group were detected by immunohistochemistry.Results There was no positive DSA in the normal group and the sham group.The inferior vena cava lumen in the posterior segment of the liver was narrowed,the distal end was dilated,and the collateral circulation was seen.There was no positive expression in HE staining and immunohistochemistry in the normal group and the sham group.The pathological damage of the liver gradually increased in the model group with the prolongation of obstruction time.The ADC values of the model group at 1,4,8 and 12 week postoperative[(1.23±0.08),(1.03±0.09),(1.12±0.09),(1.18±0.07)]were lower than those of the normal group and the sham group(P<0.05).The ADC value in the model group decreased first and then increased,lowest at the 4 week postoperative.The mRNA and protein expressions of HIF-1αand NF-κB in the model group were higher than those in the normal group and the sham group at 1,4,8 and 12 week postoperative(P<0.05).The levels of HIF-1αand NF-κB in the model group increased first and then decreased,highest at the 4 week postoperative.There was a positive correlation between HIF-1αand NF-κB in the model group(r=0.960,P=0.001).ADC values were negatively correlated with HIF-1α(r=-0.718,P=0.001)and NF-κB(r=-0.699,P=0.001)in the model group.Conclusion The ADC value of liver in BCS rats model is correlated with HIF-1αand NF-κB,and is closely related to the degree of congestion and hypoxia,which can be used as a new choice for non-invasive assessment of BCS liver injury.