抗P-选择素功能域单抗对急性肾损伤防治及免疫防御功能的影响

Effect of anti-P-selectin lectin-EGF domain monoclonal antibody on rat acute renal injury and immune defensive function in rats

目的 探讨抗P-选择素lectin-EGF功能域单抗(PsL-EGFmAb)对大鼠急性肾损伤防治及机体免疫防御功能影响。方法 建立大鼠肾缺血再灌注损伤模型,观察和比较经PsL-EGFmAb及其配体拮抗剂N-去硫酸肝素处理前后,大鼠肾组织P-选择素及其mRNA表达、组织病理学改变、肾功能变化以及免疫细胞功能状态。结果 肾缺血再灌注后,大鼠肾内以肾小管上皮细胞为主P-选择素表达增强,出现明显的组织病理学改变及肾功能损害;同时体内T、B细胞活性受抑,而NK细胞明显激活。经给予PsL-EGFmAb及其配体拮抗剂N-去硫酸肝素处理后,肾组织P-选择素及其mRNA表达受抑,病理学改变及肾功能损害减轻,尤以PsL-EGFmAb治疗效果更为明显;此外大鼠体内三种免疫细胞功能均受到不同程度的调节。结论 抗P-选择素功能域单抗对肾缺血再灌注损伤具有防治作用,其抗黏附靶向效果强于N-去硫酸肝素,并对大鼠免疫防御功能可能具有调节作用。

Objective To investigate the effect of anti-P-selectin lection-EGF domain monoclonal antibody ( PsL-EGFmAb) on acute renal injury and immune defensive function in rats. Methods The model of rat renal ischemi-a/reperfusion injury was established. We observed the change of P-selectin and its mRNA expression, histopathologi-cal alteration and renal function, immune cell's activity, after different groups of rats were treated with PsL-EGFmAb, anti-P-selectin monoclonal antibody( PsmAb) and N-Desulfated heparin, respectively. Results P-selectin expression was increased in the rat kidney especially in the renal tubular epithelial cells after ischemia/reperfusion injury, and prominent histopathologieal alterations and renal function lesion were observed, and T cell and B cell were repressed, NK cell was obviously activated. But P-selectin expression was restrained and renal pathological alteration , observed by microscopy was relieved by treatment with PsL-EGFmAb and N-desulfated heparin; the protective effect of PsL-EGFmAb was more transparent than and N-desulfated heparin. Three immune cells' functions were adjusted. Conclusion PsL-EGFmAb has preventive and curative effects on renal ischemia/reperfusion injury, and its target effect is stronger than N-desulfated heparin. PsL-EGFmAb might adjust immune defensive function of the rat body.