Ability of low-molecular-weight heparin to alleviate proteinuria by inhibiting respiratory syncytial virus infection.
OBJECTIVE
Low-molecular-weight heparin (LMWH) is a negatively charged glycoprotein and has a very similar structure to that of cell surface heparin sulfate (HS). Thus, LMWH, an analog of HS, may inhibit positively charged respiratory syncytial virus (RSV) infection through cooperative electrostatic association.


METHODS
In this study, rats were respectively treated with 400 IU/kg LMWH before, during or after being inoculated with 6 x 10(6) plaque-forming unit (PFU) RSV. RSV and normal control groups were respectively inoculated by RSV and virus-free Dulbecco's modified Eagle's medium (DMEM). HeLa cells in vitro were pretreated with LMWH, elastase (ELA), heparinase (HpaIII) and protamine before being inoculated with 6 x 10(1) PFU RSV. RSV infectivity was determined by in situ hybridization and plaque assay.


RESULTS
After inoculation, the urinary protein excretion and serum parameters in LMWH-treated rats were significantly lower than those in the RSV group. No abnormalities of glomerular structure were observed in LMWH-treated groups whereas swelling and slight hypercellularity in minority glomeruli and foot process effacement were observed in the RSV group. RSV RNA of LMWH-treated rats had weaker expression than that of the RSV group. In vitro, RSV infection in RSV + LMWH, HpaIII + ELAI, protamine + ELAI, ELAI, HpaIII and protamine treatment cells were significantly lower than that of the RSV control, and that in RSV + LMWH was the least. There were no significant differences in RSV infection between ELAI + LMWH and RSV control.


CONCLUSIONS
Our study confirmed that there is a correlation between RSV and proteinuria in rats. LMWH can alleviate proteinuria in rats through inhibiting RSV from binding with HS which plays an important role in the onset of RSV infection.
Guo
Yannan
Y
Department of Paediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Wang
Zheng
Z
Dong
Liqun
L
Wu
Jin
J
Zhai
Songhui
S
Liu
Desong
D
D000818:Animals; D006367:HeLa Cells; D019763:Heparin Lyase / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D010196:Pancreatic Elastase / Q000494:pharmacology; D011479:Protamines / Q000494:pharmacology; D011507:Proteinuria / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000473:pathology
D006495:Heparin, Low-Molecular-Weight; D011479:Protamines; D010196:Pancreatic Elastase; D019763:Heparin Lyase