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中华肝脏外科手术学电子杂志 ›› 2017, Vol. 06 ›› Issue (03) : 222 -227. doi: 10.3877/cma.j.issn.2095-3232.2017.03.016

所属专题: 文献

基础研究

分泌IGF-1的间充质干细胞对肝脏缺血-再灌注损伤的保护作用
丁凡1, 陈文捷2, 汪国营1, 冯啸1, 唐晖1, 许赤1,()   
  1. 1. 510630 广州,中山大学附属第三医院肝脏外科
    2. 510630 广州,中山大学附属第三医院生物治疗中心
  • 收稿日期:2017-02-10 出版日期:2017-06-10
  • 通信作者: 许赤
  • 基金资助:
    广东省自然科学基金(2015A030312013)

The protective effect of IGF-1-secreting mesenchymal stromal cell on liver ischemia-reperfusion injury

Fan Ding1, Wenjie Chen2, Guoying Wang1, Xiao Feng1, Hui Tang1, Chi Xu1,()   

  1. 1. Department of Hepatic Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
    2. Cell-gene Therapy Translational Medicine Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
  • Received:2017-02-10 Published:2017-06-10
  • Corresponding author: Chi Xu
  • About author:
    Corresponding author: Xu Chi, Email:
引用本文:

丁凡, 陈文捷, 汪国营, 冯啸, 唐晖, 许赤. 分泌IGF-1的间充质干细胞对肝脏缺血-再灌注损伤的保护作用[J]. 中华肝脏外科手术学电子杂志, 2017, 06(03): 222-227.

Fan Ding, Wenjie Chen, Guoying Wang, Xiao Feng, Hui Tang, Chi Xu. The protective effect of IGF-1-secreting mesenchymal stromal cell on liver ischemia-reperfusion injury[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2017, 06(03): 222-227.

目的

探讨分泌胰岛素样生长因子1的间充质干细胞(IGF-1-MSC)对小鼠肝脏缺血-再灌注损伤(IRI)的作用。

方法

50只C57BL/6系小鼠按随机数字表法随机分为IRI组、PBS组、MSC组、IGF-1-MSC组、对照组,各10只。建立小鼠肝脏IRI模型,缺血时间60 min,再灌注时IRI组不做处理,PBS组经门静脉注射PBS溶液100 μl,MSC组经门静脉注射MSC细胞悬液100 μl,IGF-1-MSC组经门静脉注射IGF-1-MSC细胞悬液100 μl。检测AST、ALT、乳酸脱氢酶(LDH)水平,并行肝组织病理学检查及TUNEL染色。各组检测指标比较采用单因素分析和LSD-t检验或Kruskal-Wallis检验。

结果

再灌注后24 h,IGF-1-MSC组AST、ALT、LDH分别为(815±233)、(867±350)、(845±358)U/L,明显低于MSC组的(3 805±1 355)、(2 421±845)、(2 011±162)U/L(LSD-t=-4.865,-3.725,-6.637;P<0.05)。IGF-1-MSC组肝窦轻度淤血,少量肝细胞凋亡;而IRI组肝细胞大量凝固性坏死和细胞凋亡。IGF-1-MSC组24 h肝组织损伤Suzuki评分为4(3~4)分,明显低于MSC组和IRI组的5(4~5)和8(7~10)分(Z=-2.545,-2.703,P<0.05)。

结论

IGF-1-MSC输注能有效减轻肝脏IRI程度,减少肝细胞凋亡可能是其保护作用机制之一。

Objective

To investigate the effect of insulin-like growth factor 1-secreting mesenchymal stromal cell (IGF-1-MSC) on liver ischemia-reperfusion injury (IRI) in mice.

Methods

According to the random number table method, 50 C57BL/6 mice were randomly divided into the IRI group, PBS group, MSC group, IGF-1-MSC group and control group with 10 mice in each group. The hepatic IRI models of mice were established and the ischemia time was 60 min. During reperfusion, no interventions were delivered in the IRI group, the mice were injected with 100 μl PBS through portal vein in the PBS group, 100 μl MSC suspension in the MSC group and 100 μl IGF-1-MSC suspension in the IGF-1-MSC group. The levels of AST, ALT and lactic dehydrogenase (LDH) were detected. Liver tissues were collected for pathological examination and TUNEL staining. The indexes of the groups were compared using one-way analysis of variance and LSD-t test or Kruskal-Wallis test.

Results

The level of AST, ALT and LDH at 24 h after reperfusion in the IGF-1-MSC group was respectively (815±233), (867±350) and (845±358) U/L, significantly lower than (3 805±1 355), (2 421±845) and (2 011±162) U/L in the MSC group (LSD-t=-4.865, -3.725, -6.637; P<0.05). Mild sinusoid congestion and a small amount of hepatocyte apoptosis were observed in the IGF-1-MSC group, while a large number of hepatocyte coagulative necrosis and apoptosis were observed in the IRI group. The liver tissue injury Suzuki score at 24 h in the IGF-1-MSC group was 4(3-4), significantly lower than 5(4-5) in the MSC group and 8(7-10) in the IRI group (Z=-2.545, -2.703; P<0.05).

Conclusions

Injection of IGF-1-MSC can effectively alleviate the severity of liver IRI. Reducing hepatocyte cell apoptosis may probably be one of the mechanisms of the protective role of IGF-1-MSC.

图1 流式细胞术鉴定IGF-1-MSC细胞表型
图5 各组小鼠再灌注后24 h肝脏组织细胞凋亡(TUNEL ×100) 注:5a为IRI组见大量肝细胞凋亡;5b为MSC组中度肝细胞凋亡;5c为IGF-1-MSC组仅见少量肝细胞凋亡
[1]
中国医师协会器官移植分会,中华医学会外科学分会移植学组,中国肝移植注册中心科学委员会.中国移植器官保护专家共识(2016版)[J].中华外科杂志,2016, 54(8): 568-576.
[2]
Bassanello M, De Palo EF, Lancerin F, et al. Growth hormone/insulin-like growth factor 1 axis recovery after liver transplantation: a preliminary prospective study[J]. Liver Transpl, 2004, 10(5): 692-698.
[3]
English K, Wood KJ. Mesenchymal stromal cells in transplantation rejection and tolerance[J]. Cold Spring Harb Perspect Med, 2013, 3(5): a015560.
[4]
Rowart P, Erpicum P, Detry O, et al. Mesenchymal stromal cell therapy in ischemia/reperfusion injury[J]. J Immunol Res, 2015: 602597.
[5]
Lai RC, Yeo RW, Tan KH, et al. Mesenchymal stem cell exosome ameliorates reperfusion injury through proteomic complementation[J]. Regen Med, 2013, 8(2): 197-209.
[6]
Souidi N, Stolk M, Seifert M. Ischemia-reperfusion injury: beneficial effects of mesenchymal stromal cells[J]. Curr Opin Organ Transplant, 2013, 18(1): 34-43.
[7]
Bellanti F. Ischemia-reperfusion injury: evidences for translational research[J]. Ann Transl Med, 2016, 4(Suppl 1): S55.
[8]
Olthof PB, van Golen RF, Meijer B, et al. Warm ischemia time-dependent variation in liver damage, inflammation, and function in hepatic ischemia/reperfusion injury[J]. Biochim Biophys Acta, 2017, 1863(2):375-385.
[9]
Gilbo N, Catalano G, Salizzoni M, et al. Liver graft preconditioning, preservation and reconditioning[J]. Dig Liver Dis, 2016, 48(11): 1265-1274.
[10]
Vogel T, Brockmann JG, Quaglia A, et al. The 24-hour normothermic machine perfusion of discarded human liver grafts[J]. Liver Transpl, 2017, 23(2): 207-220.
[11]
Bonefeld K, Møller S. Insulin-like growth factor-I and the liver[J]. Liver Int, 2011, 31(7): 911-919.
[12]
Salso A, Tisone G, Tariciotti L, et al. Relationship between GH/IGF-1 axis, graft recovery, and early survival in patients undergoing liver transplantation [J]. Biomed Res Int, 2014: 240873.
[13]
Wang Z, Zhou J, Lin J, et al. RhGH attenuates ischemia injury of intrahepatic bile ducts relating to liver transplantation[J]. J Surg Res, 2011, 171(1): 300-310.
[14]
Li T, Yan Y, Wang B, et al. Exosomes derived from human umbilical cord mesenchymal stem cells alleviate liver fibrosis[J]. Stem Cells Dev, 2013, 22(6): 845-854.
[15]
谭浩翔,汪谦,张会迎,等.大鼠肝移植术后受体骨髓间充质干细胞输注肝内示踪与标记方法比较[J].热带医学杂志,2009, 9(6): 608-610,封3-4.
[16]
Saat TC, van den Engel S, Bijman-Lachger W, et al. Fate and effect of intravenously infused mesenchymal stem cells in a mouse model of hepatic ischemia reperfusion injury and resection[J]. Stem Cells Int, 2016: 5761487.
[17]
马毅,何晓顺,陈规划.肝脏缺血再灌注损伤与细胞凋亡[J].中国病理生理杂志,2003, 19(7): 1005-1008.
[18]
Zaouali MA, Padrissa-Altés S, Ben Mosbah I, et al. Insulin like growth factor-1 increases fatty liver preservation in IGL-1 solution[J]. World J Gastroenterol, 2010, 16(45): 5693-5700.
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