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Title: [Protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A-induced acute liver injury in mice].
Author: Bi YZ, Fan Z, Chen DF, Li SS, Wang QY, Gao PF, Wang QQ, Duan ZP, Chen Y, Kong LB, Wang YB, Hong F.
Journal: Zhonghua Gan Zang Bing Za Zhi; 2017 Mar 20; 25(3):205-210. PubMed ID: 28482408.
Abstract:
Objective: To investigate the protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A (ConA)-induced acute liver injury in mice. Methods: A total of 88 male C57BL/6 mice were randomly divided into normal control group (group C), ConA model group (group M), and human liver-derived stem cells (HYX1)+ConA group (group E); according to the interval between phosphate buffer/HYX1 injection and ConA injection, Groups M and E were further divided into 3-hour groups (M1 and E1 groups), 6-hour groups (M2 and E2 groups), 12-hour groups (M3 and E3 groups), 24-hour groups (M4 and E4 groups), and 48-hour groups (M5 and E5 groups). The levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and total bilirubin (TBil) in peripheral blood were measured, liver tissue sections were used to observe pathological changes, and the Ishak score for liver inflammation was determined. The independent samples t-test was used for comparison between groups, and P < 0.05 was considered statistically significant. Results: The levels of ALT, AST, and TBil in group C were (36.25±1.16) U/L, (120.20±5.77) U/L, and (2.20±0.23) μmol/L, respectively; the levels of ALT, AST, and TBil and Ishak score were (8 721.23±837.39) U/L, (8 110.31±290.10) U/L, (8.41±0.10) μmol/L, and (13.32±1.30), respectively, in group M1, (8 334.31±666.50) U/L, (7 560.20±760.34) U/L, (10.40±0.80) μmol/L, and (12.67±0.81), respectively, in group M2, (8 960.75±551.93) U/L, (8 535.62±675.14) U/L, (10.95±1.43) μmol/L, and (14.57±0.65), respectively, in group M3, (8 618.57±886.40) U/L, (11 440.54 ± 1 327.86) U/L, (13.30±1.86) μmol/L, and (13.21±1.06), respectively, in group M4, and (10 170.13±1 112.37) U/L, (11 470.56±1 108.40) U/L, (12.75±1.55) μmol/L, and (15.07±1.58), respectively, in group M5. The levels of ALT, AST, and TBil and Ishak score were (1 016.35±163.47) U/L, (952.30±103.91) U/L, (7.77±0.62) μmol/L, and (3.50±0.21), respectively, in group E1, (42.10±6.20) U/L, (126.72±13.33) U/L, (3.41±0.53) μmol/L, and (2.01±0.40), respectively, in group E2, (44.21±4.30) U/L, (216.71±35.88) U/L, (3.47±0.44) μmol/L, and (2.13±0.25), respectively, in group E3, (2 909.69±212.14) U/L, (2 988.43±333.70) U/L, (7.03±0.93) μmol/L, and (4.70±0.50), respectively, in group E4, and (7 874.26±799.60) U/L, (10 940.54±947.35) U/L, (10.53±1.09) μmol/L, and (8.60±0.83), respectively, in group E5. Groups M1-M5 had significantly higher levels of ALT, AST, and TBil than group C (all P < 0.01), and groups M1-M4 had significantly higher levels of AST and ALT than groups E1-E4 (all P < 0.01), while there were no significant differences in the levels of AST and ALT between groups M5 and E5 (both P > 0.05). The pathological sections of liver tissue showed that compared with group M, group E had significant reductions in the degree of necrosis and Ishak score (both P < 0.05). Conclusion: Intraperitoneal transplantation of human liver-derived stem cells has a protective effect against ConA-induced acute liver injury in mice, and the injection at 6 and 12 hours in advance has the best protective effect. 目的： 探讨人肝源性干细胞腹腔移植不同时间在刀豆蛋白A（ConA）诱导小鼠急性肝损伤中的保护作用。 方法： 将88只雄性C57BL/6小鼠随机分成3组，正常小鼠对照组（C组），ConA模型组（M组），人肝源性干细胞（HYX1）+ ConA组（E组），M组和E组根据注射磷酸盐缓冲液或HYX1后再注射ConA间隔时间不同，又分为3 h（M1、E1）、6 h（M2、E2）、12 h（M3、E3）、24 h（M4、E4）、48 h（M5、E5）组。检测外周血丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、总胆红素（TBil）水平；小鼠肝组织切片观察各组病理变化，并进行肝脏炎症活动度Ishak评分。采用独立样本t检验进行组间比较，P < 0.05为差异有统计学意义。 结果： C组的ALT、AST及TBil分别为(36.25±1.16) U/L、(120.20±5.77) U/L、(2.20±0.23) μmol/L；M1～M5组的ALT、AST、TBil及肝脏Ishak评分分别为（8 721.23±837.39）U/L、（8 110.31±290.10） U/L、(8.41±0.10) μmol/L、13.32±1.30，(8 334.31±666.50) U/L、(7 560.20±760.34) U/L、(10.40±0.80) μmol/L、12.67±0.81，(8 960.75±551.93) U/L、(8 535.62±675.14) U/L、(10.95±1.43) μmol/L、14.57±0.65，（8 618.57±886.40）U/L、(11 440.54±1 327.86) U/L、(13.30±1.86) μmol/L、13.21±1.06，(10 170.13±1 112.37) U/L、(11 470.56±1 108.40) U/L、(12.75±1.55) μmol/L、15.07±1.58；E1～E5组的ALT、AST、TBil及肝脏Ishak评分分别为（1 016.35±163.47）U/L、(952.30±103.91) U/L、(7.77±0.62) μmol/L、3.50±0.21，(42.10±6.20) U/L、(126.72±13.33) U/L、(3.41±0.53) μmol/L、2.01±0.40，(44.21±4.30) U/L、(216.71±35.88) U/L、(3.47±0.44) μmol/L、2.13±0.25，(2 909.69±212.14) U/L、(2 988.43±333.70)U/L、(7.03±0.93) μmol/L、4.70±0.50，(7 874.26±799.60) U/L、(10 940.54±947.35)U/L、（10.53±1.09）μmol/L、8.60±0.83。M1～M5组的AST、ALT及TBil水平显著高于C组，差异均有统计学意义(P值均< 0.01)；M1～M4组的AST、ALT水平显著高于E1～E4组(P值均< 0.01)；而M5组与E5组的AST、ALT水平差异均无统计学意义(P值均> 0.05)。小鼠肝组织病理切片显示，E组小鼠肝组织坏死程度较M组均明显减轻，Ishak评分均明显低于M组，差异均有统计学意义（P值均< 0.05）。 结论： 腹腔肝源性干细胞移植对ConA诱导的小鼠急性肝损伤具有保护作用，尤以提前6 h和12 h注射组保护效果最明显。.

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