Comparative analysis of diuretic activities of human ANP gene injected intramuscularly and intravenously in adriamycin-induced nephrotic rats / 生物工程学报

ABSTRACT

In order to explore the feasibility of gene therapy strategy based on the human atrial natriuretic peptide (hANP) gene delivery for the treatment of nephropathy and compare the diuretic activities of the hANP gene injected intramuscularly(i.m.) and intravenously(i.v.), the naked retroviral vector DNA harboring the hANP cDNA under the control of retroviral 5' long terminal repeat at a dose of 5 mg/kg body weight was injected i.m. or i.v. into the nephrotic model rats induced with adriamycin(ADR) injected i.v. at a dose of 7.5 mg/kg body weight. A single injection of the hANP gene resulted in a marked elevation in plasma level of hANP 5 days after gene delivery and a significant increase in the ratio of urine volume to body weight and the diuretic effect continued for more than 15 days. In addition, there was a significant rise in the body weight of treatment groups as compared with that of negative control group and no difference in the concentrations of electrolytes in urine between groups. There was no significant differences in total effects resulted from the two routes of gene delivery and the way of gene delivery through the skeletal muscle is simpler and easier. These results suggest that somatic gene delivery of the hANP gene could enhance the renal functions in nephrotic rats significantly and would be a potential strategy for the treatment of renal disorders.