抗肿瘤坏死因子-α单克隆抗体减轻肾脏缺血再灌注损伤的实验研究

Effect of anti-tumor necrosis factor-αmonoclonal antibody in alleviating renal ischemia-reperfusion injury

目的研究抗肿瘤坏死因子-α单克隆抗体(anti-TNF-αmAb)对肾脏缺血再灌注损伤的作用。方法SD大鼠50只,随机分为A组(治疗组)、B组(非治疗组)和C组(假手术组),其中A、B组建立肾缺血再灌注模型。A组于再灌注前5 min经尾静脉注射anti-TNF-αmAb(0.1 mg/kg·b.w.);B组于再灌注前5 min经尾静脉注射等量生理盐水;C组仅作麻醉、开腹,不阻断血流。采用全自动生化分析仪、酶联免疫吸附实验(ELISA)、HE染色、TUNEL法及电镜分别测定或观察血肌酐、尿素氮、血浆TNF-α、肾组织病理改变、肾细胞凋亡情况及超微结构改变。结果A组血肌酐、尿素氮、血浆TNF-α水平显著低于B组(P<0.01),肾组织形态学及超微结构无明显改变,细胞凋亡显著减少。结论anti-TNF-αmAb能有效减轻肾脏缺血再灌注损伤,缓解肾功能下降。

Objective To investigate the effect of anti-tumor necrosis factor-αmonoclonal antibody (anti-TNF-αmAb) in alleviating renal ischemia-reperfusion injury. Methods Fifty normal male Sprague-Dawley rats were randomly divided into 3 groups, namely group A that was subjected to ischemia-reperfusion injury with intravenous administration of anti-TNF-αmAb (0.1mg/ kg·b.w.) 5 min before reperfusion (treatment group), group B with the same injury followed by saline administration in the same manner (control group), and group C with only anesthetization and leparotomy but not ischemia (sham operation group). Routine assays were performed for testing the levels of blood creatine (Cr), blood urea nitrogen (BUN), plasma TNF-αand the cell apoptosis. Ultrastructure of the kidney was also observed. Results Renal ischemia-reperfusion resulted in significant increase of the levels of Cr, BUN and TNF-αin the plasma (P<0.01), but these effects were offset by administration of anti-TNF-αmAb (P<0.01). In group B, widespread pathological changes and cell apoptosis were observed in the renal tissue following renal ischemia-reperfusion injury, while similar changes were scarcely visible in group A due to the protective effect of intravenous administration of anti-TNF-αmAb 5 min before reperfusion. Conclusion Renal ischemia-reperfusion injury can be alleviated by anti-TNF-αmAb treatment.