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Chinese Journal of Hepatic Surgery(Electronic Edition) ›› 2020, Vol. 09 ›› Issue (04): 374-379. doi: 10.3877/cma.j.issn.2095-3232.2020.04.018

Special Issue:

• Basic Research • Previous Articles     Next Articles

Protection of Nrf2-overexpressing human umbilical cord mesenchymal stem cells on hepatic ischemia-reperfusion injury in mice

Rongqiang Liu1, Guozhen Lin2, Tianxing Dai2, Mingbin Deng2, Chaorong Zhou3, Guoying Wang2,()   

  1. 1. Department of Liver Surgery, Liver Transplant Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China; Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510030, China
    2. Department of Liver Surgery, Liver Transplant Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
    3. Department of General Surgery, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510220, China
  • Received:2020-04-18 Online:2020-08-10 Published:2020-08-10
  • Contact: Guoying Wang
  • About author:
    Corresponding author: Wang Guoying, Email:

Abstract:

Objective

To explore the protection of Nrf2-overexpressing human umbilical cord mesenchymal stem cells (HUCMSCs) on hepatic ischemia-reperfusion injury (IRI) in mice.

Methods

A model of partial (70%) hepatic IRI was constructed. HUCMSCs were isolated, cultured and identified, and Nrf2-overexpressing lentiviral was constructed. 40 healthy male C57 mice of SPF grade were randomly divided into 4 groups according to the random number table: Sham group, IRI group, IRI+GFP-HUCMSCs group, and IRI+Nrf2-HUCMSCs group. For IRI+GFP-HUCMSCs and IRI+Nrf2-HUCMSCs group, 1×106 GFP-HUCMSCs, and 100 μl of Nrf2-HUCMSCs cell suspension were injected in the inferior vena cava of mice respectively after 90 min of ischemia. The mice were executed after 12 or 24 h of reperfusion, and then blood was taken from the inferior vena cava for ALT and AST test. Liver injury and cell apoptosis were observed through HE and TUNEL staining of liver tissue. Transaminases levels of each group were compared using univariate analysis and LSD-t test.

Results

After 12 h of reperfusion, hepatocyte damage was significantly milder in the IRI+Nrf2-HUCMSCs group than that in the IRI and GFP-HUCMSCs groups. After 24 h of reperfusion, inflammatory cell infiltration receded and recovered more quickly in the IRI+Nrf2-HUCMSCs group. After 12 hof reperfusion, the ALT and AST levels were respectively (1 472±540), (1 592±596) U/L in the IRI+Nrf2-HUCMSCs group, which were significantly lower than (4 700±1 526), (5 464±1 210) U/L in the IRI+GFP-HUCMSCs group, and (7 452±1 637), (6 928±2 439) U/L in the IRI group (LSD-t=-4.460, -7.757 and -6.420, -4.753; P<0.05). After 12 h of reperfusion, the rate of hepatocyte apoptosis was (40±6)% in the IRI+Nrf2-HUCMSCs group, significantly lower than (79±6)% in the IRI+GFP-HUCMSCs group and (103±6)% in the IRI group (LSD-t=-8.162, -13.040; P<0.05).

Conclusions

HUCMSCs overexpressing Nrf2 may exert certain protective effects on hepatic IRI by reducing the hepatocyte apoptosis in healthy mice.

Key words: Mesenchymal stem cells, Nuclear factor E2-related factor 2 (Nrf2), Ischemia-reperfusion injury, Liver injury, Apotosis, Mouse

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