氯化钆抑制大鼠肝移植急性排斥反应的机理

Effect of gadolinium chloride on suppressing acute rejection following liver allograft transplantation in the rats

目的 探讨氯化钆抑制大鼠肝移植急性排斥反应的机理。方法分别采用健康雄性Wistar和SD大鼠作为供、受者。随机分为A组(假手术对照):SD大鼠10只,开腹后不作任何处理,关腹结束手术;B组(氯化钆预处理+肝移植):受者1 5只,供者在移植前进行氯化钆预处理2 d,再获取供肝移植给受者;C组(生理盐水预处理+肝移植):受者15只,供者用生理盐水代替氯化钆预处理,其余处理同B组。分别检测各组的术后生存率、肝功能、肝脏病理组织学、肝组织和胆汁中细胞因子表达、枯否氏细胞核转录因子κB(NF-κB)以及细胞膜表面分子的表达情况。结果(1)B组术后1个月生存率明显高于C组(P<0.01)。(2)B组术后肝功能逐渐恢复正常,C组肝功能进行性恶化;B组肝组织病理学改变轻微,C组出现典型急性排斥改变。(3)B组肝组织和胆汁中γ-干扰素(IFN-γ)和白细胞介素2 (IL-2)较A组明显降低(P<0.05),IL-10较A组明显升高(P<0.05),IL-4无明显变化;C组出现与之相反的变化。(4)C组枯否氏细胞NF-κB活性明显高于A、B两组(P<0.01)。(5)B组枯否氏细胞膜表面主要组织相容性抗原复合物(MHC)、CD80、CD86分子明显低于A组(P<0.05),C组高表达上述膜表面分子。结论氯化钆能够有效地抑制枯否氏细胞的免疫活性,从而抑制大鼠同种肝移植后急性排斥反应的发生。

Objective To investigate the mechanism of gadolinium chloride (GdCl3) inhibiting Kupffer cells (KCs) to suppress acute rejection following liver allograft transplantation in the rats. Methods The rats were randomly divided into control group (A), liver transplantation with GdCl3 pretreatment group (B), and liver transplantation with normal saline pretreatment group (C). The survival rate, liver function, hepatic pathological histology, cytokine level in liver and bile, activity of NF-κB in KCs, and membraneous molecules on the KCs were observed. Results (1) The one-month survival rate in group B was significantly higher than that in group C (P<0. 05). (2) The liver function in group B gradually recovered after operation, but it progressively deteriorated in group C. There was minor change of hepatic pathological histology in group B, but typical acute rejection changes occurred in group C. (3) The levels of IFN-γ and IL-2 in group B was significantly lower, while IL-10 greatly higher than those in groups A and C (all P<0. 01). The IL-4 altered slightly in group B. (4) The activity of NF-κB in group C was significantly higher than that in groups A and B (P<0. 01). (5) The amount of MHC, CD80, CD86 on KCs membrane in group B was significantly lower than that in group A (P<0. 05), but these membranous proteins were highly expressed in group C. Conclusion GdCl3 could efficiently inhibit the immunologic activity of KCs and suppress acute rejection after liver allograft transplantation in the rats.