甘氨酸对大鼠肝移植缺血再灌注损伤库普弗细胞CD14和核因子-κB的影响

The effect of glycine on CD14 and NF-kappa B in Kupffer cells from rat liver grafts after ischemia-reperfusion injury

目的 探讨甘氨酸对大鼠肝移植缺血再灌注损伤库普弗细胞CD14和核因子-κB(NF-κB)的影响。 方法 将大鼠分为肝移植缺血再灌注组、等渗盐水预处理组、甘氨酸预处理组,检测再灌注后受体存活率、肝脏功能和病理组织学改变。分离培养再灌注后库普弗细胞,检测细胞CD14 mRNA的表达、NF-κB活性、培养上清液肿瘤坏死因子α和白细胞介素-1分泌情况。 结果 甘氨酸预处理能明显提高大鼠术后1周存活率(x2值分别为6.67和8.57,P值均<0.0 1)、改善肝功能、减轻肝脏病理组织学改变;甘氨酸预处理能明显下调库普弗细胞CD14 mRNA的表达(F=7.64,P<0.01)、降低NF-κB活性(F=11.47,P<0.01)、减少上清液肿瘤坏死因子α和白细胞介素-1分泌(F值分别为14.08和9.56,P值均<0.01)。 结论 甘氨酸能够有效地减轻肝移植后缺血再灌注损伤,其机制可能与抑制库普弗细胞CD14表达和NF-κB活性、减少肿瘤坏死因子α和白细胞介素-1的分泌有关。

Objective To investigate the effect of glycine on CD 14 and NF- κB in Kupffer cells from rat liver grafts after ischemia-reperfusion injury (IRI). Methods The rats were randomly divided into an IRI group, saline solution preconditioning group, and glycine preconditioning group. Their survival rates, graft functions, and hepatic histopathologic examinations were observed after IRI. Kupffer cells (KCs) following IRI were isolated and cultured to detect CD14 mRNA, NF- κB binding activity, and the TNFα and IL-1 level in the supernatant of the media. Results (1) Glycine preconditioning greatly enhanced the one-week survival rate ( x2 = 6.67 and 8.57 respectively, P < 0.01), improved graft function, and ameliorated the histopathologic signs of injury. (2) The CD14 mRNA expression level (F = 7.64), NF- κB binding activity (F = 11.47), TNFα and IL-1 production (F = M.08 and 9.56 respectively) in the glycine group were significantly lower than those in the other two groups (P < 0.01). Conclusion Glycine could efficiently protect rat liver grafts from ischemia-reperfusion injury by repressing the expression of CD14 and NF- κB binding activity in Kupffer cells and inhibiting the productions of TNF α and IL-1.