期刊
DIABETES
卷 53, 期 10, 页码 2723-2730出版社
AMER DIABETES ASSOC
DOI: 10.2337/diabetes.53.10.2723
关键词
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资金
- NHLBI NIH HHS [HL-66949] Funding Source: Medline
- NICHD NIH HHS [HD-39768] Funding Source: Medline
- NIDDK NIH HHS [DK-55045, DK-44935, DK-57267] Funding Source: Medline
- NIGMS NIH HHS [GM-34534] Funding Source: Medline
- NINDS NIH HHS [NS-44323] Funding Source: Medline
Diabetic cystopathy is one of the common complications of diabetes and current therapy is limited. In the present study, the effects of gene therapy, using replication-defective herpes simplex virus type 1 (HSV-1) vectors to deliver and express the nerve growth factor (NGF) gene (HSV-NGF) on tissue NGF levels and bladder function, were evaluated in streptozotocin (STZ)induced diabetic rats. Diabetic rats exhibited a significant decrease in NGF levels in the bladder and lumbosacral dorsal root ganglia (DRG) detected by enzyme-linked immunosorbent assay and displayed marked bladder dysfunction 12 weeks after STZ injection. In contrast, rats with bladder wall injection of the NGF expression vector 8 weeks after STZ treatment exhibited a significant increase of NGF levels in the bladder and L6 DRG 4 weeks after HSV-NGF injection. Along with the restoration of tissue NGF expression, in metabolic cage studies and cystometry, HSV-NGF-injected rats also showed significantly reduced bladder capacity and postvoid residual volume than diabetic rats injected with the control vector (HSV-lacZ), indicating that voiding function was improved after HSV vector-mediated NGF gene delivery. Thus, HSV vector-mediated NGF gene therapy may prove useful to restore decreased NGF expression in the bladder and bladder afferent pathways, thereby improving hypoactive bladder function in diabetes.
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