论文部分内容阅读
目的:探讨细胞间粘附分子1(ICAM1)的反义寡核苷酸药物经静脉注射后在小鼠肾脏中的分布情况及其对肾脏炎性病变时局部ICAM1表达的影响。方法:采用FITC荧光标记的ICAM1反义寡核苷酸(iASON)以不同的剂量经静脉注射后观察其在小鼠体内的分布状况及其对正常小鼠脾脏和单侧输尿管梗阻小鼠梗阻肾组织ICAM1mRNA表达的阻断效应。结果:小鼠在注药24h后,于双肾近曲小管上皮细胞内及刷状缘上可见有明显的荧光沉积,但在肾小球及间质中未发现有荧光沉积,在肝、肺、脾组织中可见少量散在的荧光分布。静脉注射1mg·kg-1和10mg·kg-1的iASON均可明显抑制正常小鼠脾脏及单侧输尿管梗阻小鼠梗阻侧肾内ICAMImRNA的表达。结论:ICAM1反义寡核苷酸可以明显阻断肾脏炎症部位ICAMImRNA的表达,其作用的良好靶器官是肾脏的近端肾小管。
Objective: To investigate the distribution of ICAM1 antisense oligonucleotide drugs in mouse kidney after intravenous injection and its effect on ICAM1 expression in renal inflammatory lesions . Methods: FITC fluorescence-labeled ICAM 1 antisense oligonucleotide (iASON) in different doses after intravenous injection to observe its distribution in mice and its normal mice spleen and unilateral ureteral obstruction in mice Blocking effect of ICAM1 mRNA expression in obstructive kidney. Results: The mice showed obvious fluorescence deposition in proximal tubule epithelial cells and brush border after 24h injection, but no fluorescence deposition was found in glomeruli and interstitium. , A small amount of sporadic fluorescence distribution can be seen in the spleen. Intravenous administration of 1 mg · kg-1 and 10 mg · kg-1 of iASON can significantly inhibit the normal mouse spleen and unilateral ureteral obstruction in renal obstructive renal ICAM I mRNA expression. Conclusion: ICAM 1 antisense oligonucleotide can significantly block the expression of ICAM I mRNA in the kidney inflammation site, its role in a good target organ is the proximal renal tubules.