AB036. Effects and its potential mechanisms of Cox-2 inhibitors on ejaculation latency of rat with experimental autoimmune prostatitis

Background: To investigate the effects and its potential mechanisms of Cox-2 inhibitors on ejaculation latency of rat with experimental autoimmune prostatitis (EAP).

Methods: Thirty six male Wistar rats with normal sexual function were screened by using the copulatory test, and were randomly divided into 3 groups: the model group (n=16), the normal control group (n=10) and the celecoxib treatment group (n=10). EAP rat model was established in the model group and the celecoxib treatment group by subcutaneous multiple point’s injection of male prostate gland extract emulsified in an equal volume of Freund’s adjuvant at the 0 and 21th day. Control animals received equal volume of saline. From the 0th day, the celecoxib treatment group was given a gavage of celecoxib (18 mg·kg^-1·d^-1), the model group and the normal control group were given a gavage of saline (0.1 mL·kg^-1·d^-1). Eight weeks later, the sexual behavior was investigated by the copulatory test, the morphological change of prostatic tissue was observed by light microscopy after HE staining, cytokines (TNF-α, IL-1β) in serum were detected by ELISA, the levels of 5-HT, 5-HT1A receptor, 5-HT2C receptor and SERT in T13-L2 and L5-S2 spinal cord tissue were detected by immunohistochemical staining and Western Blot.

Results: In model group, prostatic inflammation was found in 12 rats, and not in another 4 rats. The 4 rats were not included in the statistical analysis. In normal control group, prostatic inflammation was not found. In the celecoxib treatment group, there was a small amount of interstitial infiltration of inflammatory cells in rat’s prostate. In the copulatory test, compared with normal control group, mount latency (ML) and intromission latency (IL) in the model group were significantly prolonged (P<0.05); ejaculation latency (EL) in the model group was significantly shortened (P<0.05). There was no significant difference in these sexual behavior parameters between the normal control group and the celecoxib treatment group (P>0.05). Serum IL-1β and TNF-α levels in the model group were significantly higher than that in the control group (P<0.01). There was no significant difference in the levels of IL-1β and TNF-α between the normal control group and the celecoxib treatment group (P>0.05). In T13-L2 spinal cord tissue, compared with normal control group, 5-HT levels in the model group were significantly lower (P<0.05), 5-HT1A receptor levels in the model group were significantly increased (P<0.05), while the 5-HT2C receptor and SERT levels in the model group did not change significantly (P>0.05). In L5-S2 spinal cord tissues, compared with normal control group, 5-HT levels in the model group were significantly lower (P<0.05), while the 5-HT1A, 5-HT2C and SERT levels in the model group increased slightly, but the differences in 5-HT1A, 5-HT2C and SERT levels between the model group and the normal control group were statistically significant (P<0.05). There were not significant differences in 5-HT, 5-HT1A, 5-HT2C and SERT levels between the normal control group and the celecoxib treatment group (P>0.05).

Conclusions: EAP shorten rat’s EL by changing the levels of 5-HT and its receptors, SERT in spinal cord. Cox-2 inhibitors can prolong EL of EAP rat, the mechanisms might be that it can relieve inflammation of the prostate, reverse the effect of EAP on spinal cord 5-HT transmitter system. Cox-2 inhibitors can be used in the treatment of premature ejaculation caused by prostatitis.

Keywords: Experimental autoimmune prostatitis (EAP); ejaculation latency (EL); premature ejaculation; Cox-2 inhibitors; serotonin