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

doi:10.3877/cma.j.issn.2095-3232.2017.03.016

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. 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. 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: chixuzoe@163.com

全文 ( ) 下载PDF ( ) 导出引用

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。

关键词: 再灌注损伤, 胰岛素样生长因子Ⅰ, 间质干细胞, 小鼠

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.

Key words: Reperfusion injury, Insulin-like growth factor I, Mesenchymal stem cells, Mice

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.

[1]	许彬, 王丽, 陈瑞, 沈奕, 陆件. 瞬时受体电位粘脂素1介导细胞自噬在远端缺血后处理保护大鼠脑缺血-再灌注损伤中的作用研究[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(03): 180-187.
[2]	李璐璐, 马利红, 金佳佳, 谷伟. 干扰素基因刺激因子通过肺巨噬细胞胞葬功能调控急性肺损伤小鼠修复的研究[J/OL]. 中华危重症医学杂志(电子版), 2024, 17(02): 97-103.
[3]	唐亦骁, 陈峻, 连正星, 胡海涛, 鲁迪, 徐骁, 卫强. 白果内酯对小鼠肝缺血再灌注损伤保护作用研究[J/OL]. 中华移植杂志(电子版), 2024, 18(05): 278-282.
[4]	王雪玲, 曹欢, 顾劲扬. 肠道菌群在器官缺血再灌注损伤中的作用及机制研究进展[J/OL]. 中华移植杂志(电子版), 2024, 18(04): 247-250.
[5]	彭瑞, 杨瑞文, 魏澹宁, 夏永良. 琥珀酸受体1加重肾脏缺血再灌注损伤的作用研究[J/OL]. 中华移植杂志(电子版), 2024, 18(03): 159-164.
[6]	孙璐, 蒋亚玲, 陈凌君. 布托啡诺对脑缺血再灌注损伤大鼠神经炎症和JAK2/STAT3信号通路的影响[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(06): 344-350.
[7]	杨阳, 王琤, 周文土, 周冰. Caveolae/Caveolin-1与膜胆固醇共同调控小鼠BMSCs成骨分化[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(03): 137-142.
[8]	阿卜杜萨拉木·图尔荪麦麦提, 吐尔洪江·吐逊, 温浩. 肝脏缺血-再灌注损伤与cGAS-STING信号通路[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 394-397.
[9]	张云飞, 吐尔洪江·吐逊. NLRP3炎症小体及其在肝脏缺血-再灌注损伤中的作用机制[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 398-403.
[10]	裴捷, 毛本亮, 郝定盈, 苑伟, 颜勇, 吴帆, 王鹏珍, 王百林. 槲皮素调控肝缺血-再灌注损伤的研究进展及应用[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(02): 244-249.
[11]	史亚波, 李扬, 黄长文. 缺血-再灌注损伤促进肝癌复发机制的研究进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 96-99.
[12]	张一绚, 韩冰, 刘超, 李思晨, 孙雪峰. 年轻化内环境改善老年小鼠肾缺血再灌注损伤诱导的肾间质纤维化[J/OL]. 中华肾病研究电子杂志, 2024, 13(03): 129-133.
[13]	李京, 牛博, 刘晓蓓, 魏新雪, 黄荣. circ-SESN2 沉默靶向调控miRNA-23a-5p/ULK1 在神经细胞氧化应激损伤中的作用机制研究[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(05): 263-272.
[14]	张艺, 任秀君, 郭孟玮, 赵雅芳, 李一凡, 李佳阳, 任晓暄, 邬继红, 卢海洋. 电针预处理对脑缺血再灌注大鼠行为学及外周血内皮祖细胞的影响[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(02): 71-77.
[15]	刘俊彬, 张晓婷, 郭镜培, 刘佳妮, 于本帅, 张可, 周斌. 熊果酸通过抑制NLRP3介导的小胶质细胞焦亡减轻脑缺血再灌注损伤的研究[J/OL]. 中华介入放射学电子杂志, 2024, 12(03): 221-227.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

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

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

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