Abstract��
OBJECTIVE: To determine the distribution of ICAM-1 antisense oligonucleotides (ASON) in kidney following intravenous administration of the ASON and to investigate its inhibition effect on the ICAM-1 expression in kidney with inflammation. METHOD: The phosphorothioate ICAM-1 ASON was synthesized and labeled with FITC.ICAM-1 ASON was given to NIH mice by intravenous injection at the dose of 1mg��kg-1or 10mg��kg-1.The distributiohn of FITC-labeled ICAM-1 ASON in kidney were determined under fluorescent microscope.The expressions of ICAM-1mRNA in the kidney of the mice were examined by Northern blotting. RESULTS: 1,The highest level of fluorescein was detected within the proximal tubules in the kidney at 24 hours after injection of ICAM-1 ASON.2,There was no difference in distribution and amount of ICAM-1 ASON whether it was administered with or without liposomeDOTAP.3,In the unilateral ureteral obstruction (UUO) mice,the distribution and the level of ICAM-1 ASON in the obstructed kidney were not different from those of the normal kidney.4,The expression of ICAM-1 protein and ICAM-1mRNA in the obstructed kidney were inhibited markedly by ICAM-1 ASON. CONCLUSION:WTBZAfter systemic administration,ICAM-1 ASON may be taken up primarily by the proximal tubular cells of the mouse kidney.The distribution and the inhibition effects of ICAM-1 ASON were idential by intravenous injection at the dose of 1mg��kg-1 or 10mg��kg-1.
Cheng Qingli,
Cheng Qingli
.Distribution of ICAM-1 antisense oligodeoxynucleotide and its inhibition effect on ICAM-1 expression in mouse kidneys[J] Chinese Pharmaceutical Journal, 1999,V34(08): 522-525