超声造影定量评估兔肝缺血再灌注损伤动态变化的实验研究

Quantitative assessment of the dynamic changes of hepatic ischemia reperfusion injury with contrast enhanced ultrasound in rabbit

目的观察兔肝缺血再灌注损伤（ischemia reperfusion injury，IRI）再灌注各个时间点超声造影参数变化的特点，并探讨其临床应用价值。方法60只新西兰大白兔随机分为假手术组及肝缺血再灌注组（IRI组），IRI组又按再灌注时间不同分为0．5h、2h、6h、12h、24h、72h共6个亚组，用无创动脉夹夹闭兔肝左叶的血供建立兔半肝IRI模型；应用超声造影观察各组肝左叶灌注情况，利用后处理软件获得超声造影参数，包括峰值强度（peak signal intensinty，PI）、达峰时间（time to peak intensinty，Tp）、曲线下面积（area under the curve，AUC）、平均渡越时间（mean transit time corresponding to the center of gravity，MTT），观察各参数变化情况；取静脉血检测丙氨酸转氨酶（ALT）及天冬氨酸转氨酶（AST），处死实验兔，取肝组织行髓过氧化物酶（MPO）检测及病理学检查，分析超声造影参数与各项检查结果的相关性。结果超声造影参数PI、Tp、AUC、MTT在IRI各组与假手术组差异均有统计学意义（P〈0．001）；PI、AUC呈整体降低趋势，并在再灌注24h达到低谷，Tp、MTT呈整体升高趋势，并在再灌注24h达到高峰。超声造影各参数与ALT、AST、MPO均有一定的相关性（P〈0．001）；其中，AUC与ALT、AST、MPO均有显著相关性（r=-0．702，-0．802，-0．846；均P〈0．001）。结论超声造影能够实时、动态、快速、无创和较客观地评估肝IRI动态变化过程中的肝功能及病理变化，有望替代有创的病理学检查，AUC是超声造影参数中评估肝IRI的最好指标。

Objective To observe the dynamic changes of hepatic ischemia reperfusion injury （IRI） by contrast enhanced ultrasound（CEUS） in rabbit model and investigate its clinical value. Methods Sixty rabbits were randomly assigned into seven groups：sham operation group and 6 hepatic IRI groups （0.5 h, 2 h,6 h, 12 h, 24 h, 72 h）. The rabbits of hepatic IRI group established as follows： the hepatic artery, portalvein and bile duct in the portal triad to the left liver lobes were interrupted for 60 rain with a vascular clip and then reflow the blood. The perfusion imaging of left liver lobe was observed and then the peak signal Intensinty （PI）, time to peak intensinty （Tp）, area under the curve （AUC）, and mean transit time （MTT） were calculated. The rabbits were sacrificed and blood samples were withdrawn for the measurement of liver enzymes aspartate aminotransferase （AST） and alanine aminotransferase （ALT）, liver samples from the left lateral were collected for the measurement of myeloperoxidase （MPO） and histologic examination. The correlation between parameters of CEUS and the test results above were analyzed. Results There were significant differences in the parameters of CEUS between hepatic IRI group and sham group （P〈0.001）. PI and AUC showed a decreased tendency and the lowest values were measured in the 24 h group. Tp and MTT showed a upward tendency and the maximum values were measured in the 24 h group. The parameters of CEUS showed correlation with ALT, AST and MPO （ P 〈0.001）. AUC showed significant correlation with ALT, AST and MPO （r = 0.702, -0.802 Conclusions CEUS can assess liver functional and pathological changes in the process of hepatic IRI in real time, dynamically, rapidly, noninvasively and objectively. It is expected to replace the invasive pathological inspection. AUC is the best index for evaluating hepatic IRI in parameters of CEUS.