Molecular Mechanism Of ED Following Cavernous Nerves Injury And Erectile Function Recovery By Reconstruction Of Cavernous Nerves

Erectile dysfunction (ED) caused by cavernous nerve (CN) injury frequently presents in clinic, especially following radical prostatectomy. In 1980s, Walsh and Donker first designed nerve-sparing prostatectomy and put it into practice. However, despite the introduction of nerve-sparing prostatectomy, a significant number of patients still developed to ED after operation, which suggests that the injury of CN is not the only cause. On the other hand, bilateral CNs have to be ablated in most cases for the sake of cancer control. For these patients, it is impossible to recover their autonomic erectile function by traditional treatment measures. In the present study, we established bilateral CN injury rat models which mimic patients who experienced radical prostatectomy, to explore pathogenesis and pathophysiologic processes of ED following radical prostatectomy, and to identify the feasibility of erectile function recovery by CN reconstruction and provide theoretical and experimental foundation for seeking better measures of prevention and treatment. The whole article was divided into 4 parts: In the first part, we explored the autonomic innervations and the characteristic of rat penis in histological structure, based on which we put forward to some notable problems on establishing erectile models with rats; then we established bilateral CN injury rat models and explored the influence of CN injury on expressions of nNOS and eNOS in penile tissue of rats; in the third part, the changes of penile histological structure following denervation and its mechanism were explored and discussed; and in the last part, we explored the feasibility of erectile reflex circuit reconstruction by autologous vein graft.Part I. Related studies on pelvic neuroanatomy of rats and establishing of cavernous nerve injury rat models1 .Anatomy of autonomic nerve innervations of rat penis and its significance Objective: To explore the role of ancillary cavernous nerves in penile erection of rats and its influence on establishing CN injury rat models. Materials and Methods:36 male SD rats (3~5 months old) were used. Detailed dissections were performed on 6 of them. Major pelvic ganglion (MPG) and its branches were identified with the aid of an operating microscope. The other 30 rats were divided into 3 groups randomly, including (I) sham-operation group, (II) bilateral main cavernous nerve (MCN) ablation group and (III) bilateral MCN and ancillary branches from MPG ablation group. 7 days and 30 days after surgery, erectile ability of the models were evaluated respectively with apomorphine test. After that, all rats were received injection of 4%flluoro-gold into bilateral corpus cavernosum of penis in anesthesia condition. 5 days later, the rat was sacrificed and its bilateral MPGs were obtained for detection of flluoro-gold with a fluorescent microscope. Results: MPG and its outflow branches (MCN and some fine fibers) can be found on the surface of dorsolateral lobes of the prostate. 7 days after surgery , the erection times of group I was 2.0+0.7 ,but no erection was found among the rats of group II and III; 30 days later, most rats of group II appeared erectile response after administration of apomorphine ,while those of group III still show no erection .But the erection times of group II (0.9+0.7) was still less than that of group I (2.8+0.6) (P<0.05). 5 days after injection of fluor-gold solution, much more and brighter positive stained neural cells were examined in major pelvic ganglions of group II than those of group III. (P<0.01) Conclusions: The tiny nerve fibers derived from MPG also play a part role in penile erection of rats, and the influence of the ancillary branches should be taken into consideration when a ED ratmodel of cavernous nerve injury is created.2. The relationship of NOS-containing nerve fibers in penile dorsal nerves and autonomic nervous systemObjective: To explore the origin of nitric oxide synthase(NOS)-containing nerve fibers in penile dorsal nerves(PDNs) and its relation with autonomic nervous system. Mate...