Anti-infection effect of human beta-defensin-2 gene therapy in a rat urinary tract infection model / 中华泌尿外科杂志

ABSTRACT

Objective To assess the human β-defensin-2 ( hBD2 ) gene therapeutic efficacy in a rat urinary tract infection (UTI) model via intravesical liposome-mediated gene transfer.Methods Fifty-six female Wistar rats (class SPF) weighting 1 80 -220 were randomly divided into an experiment group and a control group ( each n =28 ).The animals were administered either 250 μl recombinant pCAGG-hBD2 or control vector pCAGG intravesically.After 48 h,rats in both groups were infected via intravesical inoculation with 200 μl of the bacterial suspension of UTI89 ( 1 × 108 CFU/ml).The rats were sacrificed at 4,24,48,and 72 h post-inoculation.The bladders were aseptically removed and bisected.One half was fixed in neutral buffered formalin for histological analysis.The remaining half-bladders were homogenized and titered for surviving bacteria.The clean-catch urine sample from each rat was collected in sterile before they were killed for bacterial titers determined and WBC counted.Results Numbers of bacterial colony-forming unit in urine and bladders from hBD2 gene treated UTI rats were significantly lower than those from the control vector administered UTI rats at 24,36,and 72 h after infection ( P ＜ 0.05 ).The amount of WBC in urine was significantly less in the defensin group than in the control group.In addition,in vivo expression of hBD2 could reduce mucosa damage,interstitium edema and inflammatory cells infiltration in UTI animals.Conclusions The successful inhibition of UTI progression could be obtained with hBD2 gene therapy.Recombinant beta-defensin-2 could kill UTI89 in vivo and suppress the subsequent infection-induced inflammatory responses.