[Comparative analysis of diuretic activities of human ANP gene injected intramuscularly and intravenously in adriamycin-induced nephrotic rats].
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.
Li
Tao
T
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS and PUMC, Bejing 100005, China.
Liang
Hong-Yan
HY
Yan
Feng
F
Lu
Sheng-Dong
SD
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001835:Body Weight; D004195:Disease Models, Animal; D004231:Diuresis; D004317:Doxorubicin / Q000633:toxicity*; D015316:Genetic Therapy; D006801:Humans; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced / Q000628:therapy*; D011507:Proteinuria / Q000628:therapy; D051381:Rats; D017208:Rats, Wistar
D004317:Doxorubicin; D009320:Atrial Natriuretic Factor