细胞间粘附分子—1单抗防治初发期急性肾小管坏死的实验研究

Experimental study of monoclonal antibody to intercellular adhesion molecule-1 for incipient acute tubular necrosis]

OBJECTIVE: To explore the role of leukocyte adhesion in the pathophysiology of glycerol-induced acute renal tubular necrosis (ATN). METHODS: Rat models of ATN were established by intramuscular injection of glycerol in 24 Wistar rats, which were divided randomly into 3 groups of equal number according to the agents coinjected with glycerol for the prevention of ATN, with another 8 rats serving as normal control. One of the 3 groups received a monoclonal antibody (mAb) against intercellualr adhesion molecule-1 (anti-ICAM-1) and another received CD3 mAb, leaving one group untreated. Both functional impairment and histological changes in the rats were observed. RESULTS: Plasma creatinine measured 24 h after the injection of glycerol was 412.31+/-94.42 micromol/L in rats treated with anti-ICAM-1, significantly lower than that in CD3 mAb-treated rats (990.21 +/-171.25 micromol/L, P<0.05). Moderate to severe necrosis in the outer renal medulla with frequent mitoses was present in rats with ATN receiving CD3 mAB or nothing, but only mild necrosis with few mitoses occurred in merely 2 of those rats with anti-ICAM-1 treatment. CONCLUSION: Leukocytes and adhesion molecules play critical roles in the pathophysiology of glycerol-induced ATN, and anti-ICAM-1 which blocks the adhesion of the leukocytes may alleviate the pathological changes in the kidney.