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  

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

作　　者：程庆砾[1] 陈香美[1] 叶一舟[1] 张颖[1] 林洪丽[1] 李锋[1] 

机构地区：[1]中国人民解放军总医院肾病科中国人民解放军肾病中心暨重点实验室

出　　处：《中华医学杂志》1999年第7期533-537,共5页National Medical Journal of China

基　　金：国家自然科学基金;军队医学科研基金

摘　　要：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。方法将荧光标记的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反义寡核苷酸经静脉注射后主要分布于小鼠的近端肾小管上。与对照组小鼠比较，经反义寡核苷酸治疗的小鼠梗阻肾组织内ＩＣＡＭ１及Ｍａｃ１阳性细胞的表达明显减少，肾组织中ＩＣＡＭ１ｍＲＮＡ的表达也明显减少，肾小管间质中炎细胞浸润数比对照组明显减轻（１１０±１４个／ｍｍ２，２７０±１３个／ｍｍ２）、间质增宽的相对面积［（７５％±０９）％、（２５４±４０）％］、基质积聚及纤维化等病变均明显减轻。治疗组小鼠在肝脏、脾脏重量、血尿素氮、肌酐、丙氨酸转氨酶及尿蛋白的检测上与对照组小鼠相比较差异均无显著意义。结论在非免疫因素引起的肾小管间质损伤中，ＩＣＡＭ１所介导的细胞粘附反应具有重要的作用，ＩＣＡＭ１反义寡核苷酸对小鼠单侧输尿管梗阻?Objective To inhibit the expression of ICAM1mRNA with the mouse ICAM1 phosphorothioate antisense oligodeoxynucleotide (ASON) and to investigate the role of ICAM1 in the pathophysialogical process of renal injury in unilateral ureteral obstruction (UUO) animal model Methods After unilateral ureteral ligation, the mice were treated with ICAM1 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 ICAM1 protein and the number of Mac1 positive cells were measured by immunohistochemical staining The pathological changes of the obstructed kidney in the mice were analyzed by PASstainingTotal RNA renal tissue was extracted for the analysis of the ICAM1mRNA by methods of Northern blotting Results The expression of ICAM1 protein and the number of Mac1 positive cells were reduced markedly in the obstructed kidneys of the mice treated with the ICAM1 ASON(11014/mm2 vs 27013/mm2) The results of Northern blotting also showed marked decrease of the expression of ICAM1mRNA in the kidney of the mice after treatment with ICAM1 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 ICAM1 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 ICAM1 ASON, compared with those in control Oligodeoxynucleotidetreated and saline treated mice Conclusions ICAM1 is a very important factor in the pathogenesis of the UUO animal model The mouse ICAM1 ASON has therapeutic effects on the injury of the obstructed kidney without apparent side effects

关 键 词：细胞粘着分子-1 间质性肾炎 反义寡核苷酸 治疗 

分 类 号：R692.605[医药卫生—泌尿科学]