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中华医学超声杂志(电子版) ›› 2019, Vol. 16 ›› Issue (08) : 625 -630. doi: 10.3877/cma.j.issn.1672-6448.2019.08.014

所属专题: 文献

基础研究

基于压痕松弛实验的黏弹性参数评价大鼠肝纤维化的实验研究
刘冬1, 苏晨1, 钱林学1,(), 李国洋2, 曹艳平2   
  1. 1. 100050 首都医科大学附属北京友谊医院超声科
    2. 100084 北京,清华大学航天航空学院工程力学系
  • 收稿日期:2019-07-19 出版日期:2019-08-01
  • 通信作者: 钱林学

Indentation relaxation test based viscoelastic parameters for evaluation of liver fibrosis in rats

Dong Liu1, Chen Su1, Linxue Qian1,(), Guoyang Li2, Yanping Cao2   

  1. 1. Department of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
    2. Department of Engineering Mechanics, School of Aeronautics and Astronautics, Tsinghua University, Beijing 100084, China
  • Received:2019-07-19 Published:2019-08-01
  • Corresponding author: Linxue Qian
  • About author:
    Corresponding author: Qian Linxue, Email:
引用本文:

刘冬, 苏晨, 钱林学, 李国洋, 曹艳平. 基于压痕松弛实验的黏弹性参数评价大鼠肝纤维化的实验研究[J/OL]. 中华医学超声杂志(电子版), 2019, 16(08): 625-630.

Dong Liu, Chen Su, Linxue Qian, Guoyang Li, Yanping Cao. Indentation relaxation test based viscoelastic parameters for evaluation of liver fibrosis in rats[J/OL]. Chinese Journal of Medical Ultrasound (Electronic Edition), 2019, 16(08): 625-630.

目的

探讨基于压痕松弛实验的黏弹性参数评价肝纤维化的可行性,以期为弹性成像诊断肝纤维化提供有价值的参数和方法。

方法

选取雄性SD大鼠50只,平均体质量(180±20)g,将其分为2组,肝纤维化组(40只)和对照组(10只)。最终纳入43只,其中肝纤维化组36只,对照组7只。实验组大鼠采用四氯化碳-橄榄油溶液建立肝纤维化模型,对照组大鼠采用单纯橄榄油溶液灌胃。分离大鼠肝脏后进行压痕松弛实验,测算肝脏黏弹性参数。对离体肝脏病理标本进行肝组织纤维化分期(S1~S4期)。对不同肝纤维化分期的各组大鼠黏弹性参数进行比较,并进行黏弹性参数与大鼠肝纤维化程度的相关性分析。

结果

对照组与肝纤维化S1~S4期各组的黏弹性参数应力下降开始时的变化程度(g1)、应力降低到平衡时的变化程度(g2)、黏弹性材料的总松弛程度(g1g2)、应力下降开始时间(τ1)、应力降低到平衡时的时间(τ2)进行比较,τ1τ2g1组间差异有统计学意义(F=23.598、2.836、2.506,P均<0.05),进一步两两比较,黏弹性参数τ1在正常肝脏组与S1、S2、S3、S4期肝纤维化组之间的差异均有统计学意义(t=2.367、1.689、2.887、3.195,P均<0.05);黏弹性参数τ2在S1期和S3期肝纤维化组之间差异有统计学意义(t=2.048,P<0.05);黏弹性参数g1在S2期和S3期肝纤维化组之间差异有统计学意义(t=3.211,P<0.05)。Spearman相关性分析显示,黏弹性参数g1g1g2与肝纤维化程度呈正相关(r=0.513、0.439,P均<0.001),τ1与肝纤维化程度呈负相关(r=-0.509,P<0.001)。

结论

黏弹性参数与肝纤维化分期具有相关性,将黏弹性参数应用于大鼠肝脏纤维化分期的评估具有可行性,这也为黏弹性参数运用于剪切波弹性成像评价肝纤维化提供了可靠的实验论据。

Objective

To explore the feasibility of viscoelastic parameters based on the indentation relaxation test in evaluating liver fibrosis, so as to provide valuable parameters and methods for elastography in diagnosing liver fibrosis.

Methods

Fifty male SD rats with an average body mass of (180±20) g were selected and divided into two groups: a liver fibrosis group (n=40) and a control group (n=10). Finally, 43 SD rats were included, including 36 in the hepatic fibrosis group and 7 in the control group. Liver fibrosis was induced in rats with carbon tetrachloride, while the control group was fed olive oil solution alone. The indentation relaxation test was performed to determine the viscoelastic parameters of the liver after liver isolation. Liver fibrosis staging (stages S1~S4) was performed on isolated liver pathological specimens. The viscoelastic parameters of different liver fibrosis stages in rats were compared and the correlation between viscoelastic parameters and the degree of liver fibrosis in rats was analyzed.

Results

Viscoelastic parameters τ1, τ2, and g1 were statistically significant different between the groups (F=23.598, 2.836, and 2.506, respectively, all P<0.05). In further pairwise comparisons, τ1 was statistically different between the control group and group S1, S2, S3, or S4 (t=2.367, 1.689, 2.887, and 3.195, respectively, all P<0.05). τ2 was statistically different between groups S1 and S3 (t=2.048, P<0.05), and g1 was statistically different between groups S2 and S3 (t=3.211, P<0.05). Spearman correlation analysis showed that viscoelastic parameters g1 and g1+ g2 were positively correlated with the degree of liver fibrosis (r=0.513 and 0.439, respectively, both P<0.001), while τ1 was negatively correlated with the degree of liver fibrosis (r=-0.509, P<0.001).

Conclusion

Viscoelastic parameters correlate with liver fibrosis stages, so it is feasible to use viscoelastic parameters to evaluate liver fibrosis stage in rats, which provides reliable experimental evidence for the application of viscoelastic parameters in shear wave elastography to evaluate liver fibrosis.

图1 ElectroForce? 3100(Bose,Eden Prairie,MN)测试仪进行压痕松弛实验。图a为ElectroForce? 3100(Bose, Eden Prairie,MN)测试仪器;图b为通过测试仪的球形压头和肝脏组织接触并施加压力,使其产生形变后,压力传感器测量应力变化,从而得到反映肝脏黏弹性的参数
图2 大鼠肝纤维化病理切片图。图a~d分别为肝纤维化S1~S4期HE染色病理图片(×40);图e~h分别为肝纤维化S1~S4期天狼星染色病理图片(×40)
表1 不同肝纤维化分期的各组大鼠黏弹性参数比较(±s
图3 应力下降开始时的变化程度与大鼠肝纤维化程度的相关性分析散点图
图4 黏弹性材料的总松弛程度与大鼠肝纤维化程度的相关性分析散点图
图5 应力下降开始时间与大鼠肝纤维化程度相关性分析散点图
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