Adeno-associated virus-mediated insulin-like growth factor-1 in the treatment of diabetic cystopathy

Abstract

Objective To study the curative treatment role of the recombinant adeno-associated virus (rAAV)-mediated rat insulin-like growth factor-1 (IGF-1) gene on streptozotocin-induced diabetic cystopathy.Methods Forty male SD rats were divided randomly into five age-matched groups:normal control (CN,n =8),diabetes model (DM,n =8),rAAV2/1-IGF-1 transduction model (IGF-1,n =8),insulin therapy model (INS,n =8),rAAV2/1-IGF-1 transduction & insulin therapy model group (IGF-1 + INS,n =8).Eight weeks after the induction of diabetes model,insulin (6 U) and/or rAAV2/1-IGF-1 (100 μ1) was injected into rats of corresponding groups.Urinary dynamics was analyzed to evaluate the bladder function after gene therapy for 6 weeks.HE staining was used to observe the pathological changes of bladder detrusor.The expression profile of IGF-1 protein was assessed by using immunohistochemistry (IHC).Results As compared with DM group,the voiding rate in IGF-1 + INS group,INS group and IGF-1 group was significantly increased (86.59 ± 1.20,79.18 ± 1.34,77.88 ± 1.82 vs.76.16 ± 1.87,P ＜ 0.05).Detrusor muscle in DM group showed bundles derangement,loose structure,but detrusor injury severity in IGF-1 group and INS group was significantly relieved,and detusor structure performance inIGF-1 + INS group was close to the normal level.The IGF-1 expression level in bladder tissue was significantly decreased in DM group (3.37 ± 0.52) as compared with IGF-1 + INS group (4.16 ± 0.15),INS group (4.08 ± 0.30) and IGF-1 group (4.12 ± 0.35).Conclusion The decreased IGF-1 expression levels in bladder tissue may be involved in the development of diabetic cystopathy.IGF-1 gene and INS treatment may play a part role in repairing bladder function of diabetic rats. Key words: Adeno-associated virus; Insulin-like growth factor-1; Diabetes; Cystopathy