[Study of R2* value to evaluate regulation of liver regeneration by hepatic warm ischemia-reperfusion injury after partial hepatectomy in rabbits]

Zhonghua Gan Zang Bing Za Zhi. 2021 Jun 20;29(6):539-544. doi: 10.3760/cma.j.cn501113-20191214-00461.
[Article in Chinese]

Abstract

Objective: To investigate the effect of R2* value on the evaluation of different degrees of hepatic warm ischemia-reperfusion injury (WIRI) and liver regeneration after partial hepatectomy in rabbits. Methods: Thirty healthy adult male New Zealand White rabbits were randomly divided into five groups. Hepatic caudal lobectomy was performed in both the control and the warm ischemia time-dependent variation group. After reperfusion, routine MRI and BOLD MRI scans were performed for each group at 6 h, 3 d, 7 d, 14 d and 30 d, respectively, and then R2* value and liver regeneration rate (LRR) were measured and calculated. After 30 days of scanning, the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), tumor necrosis factor - α (TNF - α), interleukin-6 (IL-6) and proliferating cell nuclear antigen (PCNA) were detected in frozen rabbit liver tissues, and the pathological sections were collected. Repeated measures analysis of variance was used to evaluate the changes of R2* value, LRR and its influencing factors at different follow-up time and warm ischemia time in each group. Pearson's or Spearman's correlation analysis was used to evaluate the correlation of R2* value with LRR and various biochemical indexes. Results: The interaction between different follow-up time and warm ischemia time (F = 24.600, P < 0.001) and the single effect of the both on the R2* value had statistically significant difference (P < 0.05). The interaction of different follow-up time and different warm ischemia time had no effect on LRR, and the difference was not statistically significant (F = 0.925, P = 0.528), but the difference in the main effect of the both on LRR was statistically significant (P < 0.05). At the same follow-up time, except for the 40-min ischemia group, the R2* values ​​were significantly positively correlated with LRR (3, 7, 14, 30 days after operation, r = 0.510, 0.681, 0.612, 0.541 respectively, P < 0.05). At the same warm ischemia time, the R2* value were significantly negatively correlated with LRR (3, 7, 14, 30 and 40 days after operation, r = - 0.800, -0.852, -0.893, -0.648, -0.853, respectively, P < 0.05). There was no correlation between R2 * value and biochemical indexes at 30 days after operation (P > 0.05). Conclusion: The R2* value may be used for noninvasive and quantitative evaluation of microstructural changes of WIRI and affect liver regeneration after partial hepatectomy in rabbits. A certain degree of WIRI (≤30 min) after partial hepatectomy can promote liver regeneration in rabbits. Furthermore, as the warm ischemia time prolongs, the promoting effect becomes more pronounced, and if the warm ischemic time exceeds 30 minutes, the promoting effect is significantly reduced.

目的: 探讨R2*值评价不同程度兔肝热缺血再灌注损伤(WIRI)及其对部分肝切除术后肝再生的影响。 方法: 健康成年雄性新西兰大白兔30只,随机分为5组,即对照组和不同热缺血时间组,均行肝尾叶切除术。各组分别于再灌注6 h、3 d、7 d、14 d、30 d进行常规MR及BOLD MRI扫描。测量并计算R2*值及肝再生率(LRR)。30 d扫描结束后检测兔血清丙氨酸转氨酶、天冬氨酸转氨酶、乳酸脱氢酶水平,冻存肝组织丙二醛、超氧化物歧化酶、髓过氧化物酶、肿瘤坏死因子-α、白细胞介素-6和增殖细胞核抗原水平,并获取病理切片。采用重复测量方差分析评估各组不同随访时间、不同热缺血时间的R2*值、LRR的变化及其影响因素。采用Pearson或Spearman相关分析评价R2*值与LRR及各生化指标的相关性。 结果: 不同随访时间和不同热缺血时间的交互作用(F = 24.600,P < 0.001)及两者的单独效应对R2*值的影响差异均具有统计学意义(P值均< 0.05)。不同随访时间和不同热缺血时间的交互作用对LRR的影响差异无统计学意义(F = 0.925,P = 0.528),但二者对LRR的主效应差异均具有统计学意义(P值均< 0.05)。同一随访时间,除热缺血40 min组外,R2*值与LRR均呈显著正相关(术后3、7、14、30 d r值分别为0.510、0.681、0.612、0.541,P值均< 0.05)。同一热缺血时间,R2*值与LRR均呈显著负相关(热缺血0、10、20、30、40 min r值分别为-0.800、-0.852、-0.893、-0.648、-0.853,P值均< 0.05)。术后30 d R2*值与各生化指标无相关关系(P值均> 0.05)。 结论: R2*值可无创、定量评价兔肝WIRI的微观结构改变及其对部分肝切除术后肝再生的影响。一定程度的WIRI(≤30 min)对兔肝部分切除术后肝再生具有促进作用,且热缺血时间越长,促进作用越明显;超过30 min促进作用明显减低。.

Keywords: Blood oxygen level dependent MRI; Ischemia reperfusion injury; Liver regeneration.

MeSH terms

  • Alanine Transaminase
  • Animals
  • Aspartate Aminotransferases
  • Hepatectomy
  • Liver / diagnostic imaging
  • Liver / surgery
  • Liver Regeneration*
  • Male
  • Rabbits
  • Reperfusion Injury*

Substances

  • Aspartate Aminotransferases
  • Alanine Transaminase