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[不同时间腹腔移植人肝源性干细胞对刀豆蛋白A诱导的小鼠急性肝损伤的保护作用]

[Protective effect of intraperitoneal transplantation of human liver-derived stem cells at different times against concanavalin A-induced acute liver injury in mice].

作者信息

Bi Y Z, Fan Z, Chen D F, Li S S, Wang Q Y, Gao P F, Wang Q Q, Duan Z P, Chen Y, Kong L B, Wang Y B, Hong F

机构信息

Shandong University School of Medicine, Jinan 250012, China.

College of medicine and life science, University of Jinan, Jinan 250200, China.

出版信息

Zhonghua Gan Zang Bing Za Zhi. 2017 Mar 20;25(3):205-210. doi: 10.3760/cma.j.issn.1007-3418.2017.03.009.

Abstract

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. 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 < 0.05 was considered statistically significant. 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 < 0.01), and groups M1-M4 had significantly higher levels of AST and ALT than groups E1-E4 (all < 0.01), while there were no significant differences in the levels of AST and ALT between groups M5 and E5 (both > 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 < 0.05). 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.

摘要

探讨不同时间点腹腔移植人肝源性干细胞对刀豆蛋白A(ConA)诱导的小鼠急性肝损伤的保护作用。将88只雄性C57BL/6小鼠随机分为正常对照组(C组)、ConA模型组(M组)和人肝源性干细胞(HYX1)+ConA组(E组);根据磷酸盐缓冲液/HYX1注射与ConA注射的间隔时间,M组和E组进一步分为3小时组(M1和E1组)、6小时组(M2和E2组)、12小时组(M3和E3组)、24小时组(M4和E4组)和48小时组(M5和E5组)。检测外周血中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆红素(TBil)水平,取肝组织切片观察病理变化,并测定肝脏炎症的Ishak评分。组间比较采用独立样本t检验,P<0.05为差异有统计学意义。C组ALT、AST和TBil水平分别为(36.25±1.16)U/L、(120.20±5.77)U/L和(2.20±0.23)μmol/L;M1组ALT、AST、TBil水平及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和(13.32±1.30);M2组分别为(8 334.31±666.50)U/L、(7 560.20±760.34)U/L、(10.40±0.80)μmol/L和(12.67±0.81);M3组分别为(8 960.75±551.93)U/L、(8 535.62±675.14)U/L、(10.95±1.43)μmol/L和(14.57±0.65);M4组分别为(8 618.57±886.40)U/L、(11 440.54±1 327.86)U/L、(13.30±1.86)μmol/L和(13.21±1.06);M5组分别为(10 170.13±1 112.37)U/L、(11 470.56±1 108.40)U/L、(12.75±1.55)μmol/L和(15.07±1.58)。M1 - M5组ALT、AST和TBil水平均显著高于C组(均P<0.01),M1 - M4组AST和ALT水平显著高于E1 - E4组(均P<0.01),而M5组与E5组AST和ALT水平差异无统计学意义(均P>0.05)。肝组织病理切片显示,与M组相比,E组坏死程度和Ishak评分均显著降低(均P<0.05)。腹腔移植人肝源性干细胞对ConA诱导的小鼠急性肝损伤有保护作用,提前6小时和12小时注射保护效果最佳。

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