Adenoviral Vector-Mediated NGF Gene Therapy for a Rat Model of Diabetic Bladder Dysfunction

Abstract

Diabetes was a common complication occurred in aging populations. Diabetic bladder dysfunction (DBD) was one of the complications of diabetes. We used streptozocin (STZ) to induce diabetes in rat models. Cystometrography was performed to evaluate the function of bladder after NGF gene therapy. Histological analysis was used to observe the structure of bladder. Western blot and qPCR was performed to detect the expression level of NGF in bladder tissues. Diabetes could decrease the postvoid residual volume, bladder capacity and maximal detrusor pressure of Wistar rat in diabetic rats (DM) and DM injected with blank adenoviral vector (Ad) group. And there were no differences in bladder pressure among these groups. The results of western blot and polymerase chain reaction (PCR) indicated that the expression levels of Nerve Growth Factor (NGF) were decreased in DM and Ad groups, and increased in Ad-NGF group (P < 0.05). The results of morphological observation indicated that the structure of detrusor smooth muscle cells was broken in diabetes rats, including interruption of continuity and swelling of smooth muscle cells, and showed a time- depend manner. After the treatment of NGF gene, the structure and function of bladder were recovered, but the recovery effect of NGF gene therapy was reduced with the development of diabetes. These results indicated that diabetes could broke the structure and function of bladder, and the structure and function of bladder could restore under NGF-gene therapy in the early stage of diabetes but not the late stage. Funding: The experiment was supported by Project of PAP（CWJ18L004） and Family Planning Project of PLA(145BHQ090003076X) Declaration of Interest: None to declare. Ethical Approval: The experiments were approved by the Institution's Ethics Committee for Investigation of Tianjin Medical University, and all of the 40 animals were treated under humane care in compliance with the Public Health Service Policy on Humane Care and Use of Laboratory Animals.