细胞间粘附分子1反义寡核苷酸对小鼠肾小管间质病变的治疗作用

目的 探讨细胞间粘附分子－１（ＩＣＡＭ－１）在肾小管间质炎性病变中的作用。方法 将劳光标记的ＩＣＡＭ－１反义寡核苷酸经静脉注射至正常小鼠体内，观察其分布状况。小鼠在行单侧输尿管梗阻术后从尾静脉注射ＩＣＡＭ－１反义寡核苷酸（７只），术后第７天留取输尿管梗阻侧肾脏检测肾组织ＩＣＡＭ－１ｍＲＮＡ的表达并作病理检查。同时设立对照寡核苷酸（８只）和注射用水组（６只）作为空白对照。结果 ＩＣＡＭ－１反义寡核苷

Antisense oligonucleotide attenuates renal tubulointerstitial injury in mice with unilateral ureteral obstruction

OBJECTIVE: To inhibit the expression of ICAM-1 mRNA with the mouse ICAM-1 phosphorothioate antisense oligodeoxynucleotide (ASON) and to investigate the role of ICAM-1 in the pathophysialogical process of renal injury in unilateral ureteral obstruction (UUO) animal model. METHODS: After unilateral ureteral ligation, the mice were treated with ICAM-1 ASON, which was injected intravenously at the dosage of 1 mg/kg/day every other day for one week. Other mice treated with control oligonucleotide or normal saline solution only were taken as controls. The expression of ICAM-1 protein and the number of Mac-1 positive cells were measured by immunohistochemical staining. The pathological changes of the obstructed kidney in the mice were analyzed by PAS-staining. Total RNA renal tissue was extracted for the analysis of the ICAM-1 mRNA by methods of Northern blotting. RESULTS: The expression of ICAM-1 protein and the number of Mac-1 positive cells were reduced markedly in the obstructed kidneys of the mice treated with the ICAM-1 ASON(110 +/- 14 symbol: see text]/mm2 vs 270 +/- 13 symbol: see text]/mm2). The results of Northern blotting also showed marked decrease of the expression of ICAM-1 mRNA in the kidney of the mice after treatment with ICAM-1 ASON. There were marked inflammatory cells infiltration in the tubulointerstitium, markedly dilated tubules, and extraceliular matrix accumulation in the obstructed kidneys on the 7th day after UUO operation. The treatment of ICAM-1 ASON can alleviate the lesions of the obstructed kidney except for the dilation of the tubules. There was no difference in the body weight, liver weight, spleen weight, the level of BUN and SCr, the level of GPT as well as the urine protein of the mice treated with ICAM-1 ASON, compared with those in control Oligodeoxynucleotide-treated and saline-treated mice. CONCLUSIONS: ICAM-1 is a very important factor in the pathogenesis of the UUO animal model. The mouse ICAM-1 ASON has therapeutic effects on the injury of the obstructed kidney without apparent side effects.