Objective To explore the role of neurotrophin-3 overexpression induced pluripotent stem cells (iPSC-NT-3) in treating rats with diabetes-induced erectile dysfunction (DIED).

Methods The diabetic model rats were established by intraperitoneal injection of streptozotocin, and the DIED model was verified by subcutaneous injection of apomorphine. Twenty-four rats with successful modeling of DIED were randomly divided into model control group, induced pluripotent stem cell (iPSC) treatment group and IPSC-NT-3 treatment group; eight SD rats with intraperitoneal injection of sodium citrate and citrate buffer were selected as normal control group. Rats in each group were intraperitoneally injected with pentobarbital sodium for anesthesia, the iPSC and the iPSC-NT-3 were respectively injected into the penile sponge of rats through microinjection needle in the iPSC treatment group and the IPSC-NT-3 treatment group, and the equal volume of phosphoric acid buffer was injected by the same method in the normal control group and the model control group. At the 4th week after treatment, the general condition of the rats in each group was observed, and the sexual function and erectile function of the penis were evaluated. Quantitative polymerase chain reaction (q-PCR) and Western blot assay were used to detect the mRNA and protein expressions of neurotrophin-3 (NT-3), CD31, vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), Desmin and α-smooth muscle actin (α-SMA).

Results Before and 4 weeks after treatment, there were no significant intra-group and between-group differences in body mass and blood glucose level of rats among the model control group, the iPSC treatment group and the iPSC-NT-3 treatment group (P>0.05). In the comparison of primary time of climbing back in rats, the time in the model control group was longer than the normal control group, the time in the iPSC treatment group and the iPSC-NT-3 treatment group was shorter than the model control group, and the time in the iPSC-NT-3 treatment group was shorter than the iPSC treatment group, and all the differences were statistically significant (P < 0.05); in the comparison of licking and smelling times, riding times and inserting times, the times in the model control group were less than the normal control group, the times in the iPSC treatment group and the iPSC-NT-3 treatment group were greater than the model control group, the times in the iPSC-NT-3 treatment group was greater than the iPSC treatment group, and all the differences were statistically significant (P < 0.05). In comparison of ICP and ICP/MAP, the values in the model control group were lower than the normal control group, the values in the iPSC treatment group and the IPSC-NT-3 treatment group were higher than the model control group, and the values in the IPSC-NT-3 treatment group were higher than the iPSC treatment group, and all the differences were statistically significant (P < 0.05). In the comparison of the mRNA expression levels of NT-3, CD31, VEGF, eNOS, Desmin and α-SMA in the cavernous penis of rats, the levels in the model control group were lower than the normal control group, the levels in the iPSC treatment group and the iPSC-NT-3 treatment group were higher than the model control group, the levels in the iPSC-NT-3 treatment group were higher than the iPSC treatment group, and all the differences were statistically significant (P < 0.05). In the comparison of the protein levels of NT-3, CD31, VEGF, eNOS, Desmin and α-SMA in the cavernous penis of rats, the levels in the model control group were lower than the normal control group, the levels in the iPSC treatment group and the IPSC-NT-3 treatment group were higher than the model control group, the levels in the IPSC-NT-3 treatment group were higher than the iPSC treatment group, and all the differences was statistically significant (P < 0.05).

Conclusion The iPSC-NT-3 can improve the sexual function and erectile function of DIED rats by promoting the production of eNOS, vascular endothelium and smooth muscle in the cavernous tissues, which is a potential treatment for DIED.