Protective effect of gadolinium chloride on early warm ischemia/reperfusion injury in rat bile duct during liver transplantation.

Protective effect of gadolinium chloride on early warm ischemia/reperfusion injury in rat bile duct during liver transplantation.
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DOI:
10.1371/journal.pone.0052743
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zhou J
Zhou J
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Wang B;Zhang Q;Zhu B;Cui Z;Zhou J

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库普弗细胞(KC)的激活是胆管热缺血/再灌注损伤发生和持续的关键事件。氯化钆(GdCl 3)对KC活化的抑制作用显示出作为肝损伤保护性干预的潜力,但关于胆管损伤的研究较少。将65只雄性Sprague-Dawley大鼠(200-250 g)随机分为3个实验组:假手术组(n = 15)、对照组(n = 25)和GdCl 3组(n = 25)。      分别于术后0.5、2、6、12、24 h取材。测定血清谷丙转氨酶(ALT)、碱性磷酸酶(ALP)和总胆红素(TBIL)。检测肿瘤坏死因子-α(TNF-α)、Capase-3活性和可溶性Fas(sFas)。观察胆管的病理变化。胆管Fas免疫组化染色。UDP缺口末端标记法检测胆管细胞凋亡。GdCl 3能显著降低2、6、12和24 h的ALT、ALP和TBIL水平,升高2、6和12 h的血清sFas水平(P<0.05)。GdCl 3组TNF-α在2、6、12、24 h均低于对照组(P<0.05)。GdCl 3预处理后2、6、12、24 h,Caspase-3活性和胆管细胞凋亡均显著降低。术后2、6、12 h,GdCl 3组Fas蛋白表达均低于对照组(P<0.05)。GdCl 3在抑制胆管细胞凋亡中发挥重要作用,包括降低ALT、ALP、TBIL和TNF-α;抑制移植过程中Fas-FasL-Caspase信号转导。
Activation of Kupffer cell (KC) is acknowledged as a key event in the initiation and perpetuation of bile duct warm ischemia/reperfusion injury. The inhibitory effect of gadolinium chloride (GdCl3) on KC activation shows potential as a protective intervention in liver injury, but there is less research with regard to bile duct injury. Sixty-five male Sprague-Dawley rats (200–250 g) were randomly divided into three experimental groups: a sham group (n = 15), a control group (n = 25), and a GdCl3 group (n = 25). Specimen was collected at 0.5, 2, 6, 12 and 24 h after operation. Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin (TBIL) of serum were measured. Tumor necrosis factor-α (TNF-α), Capase-3 activity and soluble Fas (sFas) were detected. The pathologic changes of bile duct were observed. Immunochemistry for bile duct Fas was performed. Apoptosis of bile duct cells was evaluated by the terminal UDP nick end labeling assay. GdCl3 significantly decreased the levels of ALT, ALP and TBIL at 2, 6, 12, and 24 h, and increased serum sFas at 2, 6 and 12 h (P<0.05). TNF-α was lower in the GdCl3 group than in the control group at 2, 6, 12 and 24 h (P<0.05). Preadministration of GdCl3 significantly reduced the Caspase-3 activity and bile duct cell apoptosis at 2, 6, 12 and 24 h. After operation for 2, 6 and 12 h, the expression of Fas protein was lower in the GdCl3 group than in the control group (P<0.05). GdCl3 plays an important role in suppressing bile duct cell apoptosis, including decreasing ALT, ALP, TBIL and TNF-α; suppressing Fas-FasL-Caspase signal transduction during transplantation.
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