| Premature ejaculation is one of the most common male sexual dysfunctions,which seriously affects the quality of life of the patient and the relationship between the couple.Sleep deprivation,disorders or sleep disruption can lead to narcolepsy and impaired neuropsychological function,and adversely affect cardiac function.As research on sleep has intensified,it has been recognized that sleep is also strongly associated with male reproductive health.However,few studies have focused on sleep and ejaculatory function,and the mechanisms are still unclear.In this study,we constructed an animal model of primary PE to clarify whether 5-HT2 B receptors,the newest member of the 5-HT2 R family,have a key role in the regulation of ejaculation.Then,we constructed a sleep deprivation rat model to investigate whether sleep disorders affect sexual behavior by altering the expression of 5-HT and 5-HT2 B receptors,and to reveal the mechanism of this signaling pathway in the regulation of ejaculation by sleep disorders;finally,we investigated whether sleep disorders are a risk factor for the development of premature ejaculation in clinical studies.To provide a theoretical basis for exploring the pathogenesis of premature ejaculation and new ways of treatment.Part Ⅰ: Study on the mechanism of 5-HT and 5-HT2 B receptors in the regulation of ejaculatory behavior in the central nervous system in ratsObjective: To screen an animal model of primary premature ejaculation by observational method based on the ejaculatory continuum theory,and to clarify whether the 5-HT2 B receptor,the latest member of the 5-HT2 R family,has a key role in the regulation of ejaculation through an animal model of primary PE.Methods: Based on the ejaculatory continuum theory,a rat model of primary premature ejaculation was constructed to establish the 5-HT2 B and 5-HT differential expression profiles in the central system.The quantitative and localized differential expression of 5-HT2 B and 5-HT in the central system of rats with different sexual behaviors were statistically analyzed to confirm whether 5-HT2 B may have a key role in the regulation of ejaculation in rats.Results: Compared with rats in the "normal" and "delayed ejaculation" groups,rats in the " rapid ejaculation" group had shorter mount latency and intromission latency,and the number of mount and straddles before the first ejaculatory act was also shorter.The number of insertions and intromission before the first ejaculation was also less,and the time interval between ejaculation and intromission was shorter and the number of ejaculations was more frequent in the male rats.There were significant differences in 5-HT levels in the hippocampus and raphe nucleus of rats in the "rapid ejaculation","normal ejaculation" and "delayed ejaculation" groups.The 5-HT levels in the hippocampus and raphe nucleus a of rats in the "rapid ejaculation" group were significantly lower than those in the "normal ejaculation" and "delayed ejaculation" groups.In the hippocampus and raphe nucleus of the central system of rats,5-HT levels were significantly lower in the "rapid ejaculation" group than in the "normal" and "delayed" groups.The expression level of 5-HT2 B receptor protein was significantly higher in the "ejaculation overload" group than in the "ejaculation normal" and "ejaculation delayed" groups.Conclusion: We found that the central nervous system of rats with different ejaculatory behaviors had different 5-HT2 B expression.The expression of 5-HT2 B receptors in different brain regions of the central nervous system may be closely related to the different sexual behavioral characteristics of rats,suggesting that it may have a key role in the regulation of ejaculation in the central system of rats.Part Ⅱ: The study of the involvement of P2X7/5-HT2 B receptors in the central nervous system in the effect of sleep deprivation on ejaculatory behavior in rats Objective: Through the previous part of the study,we found that the central nervous system of rats with different ejaculatory behavior has different 5-HT2 B expression.In this study,we aimed to clarify whether sleep deprivation affects the sexual behavior of rats by interfering with 5-HT2 B receptors in the central system,and to investigate whether restorative sleep can reverse the negative effects of sleep deprivation through an animal model of sleep deprivation.Methods: To construct a rat sleep disorder model and restorative sleep model through sleep deprivation;to explore the role of sleep disorder in the regulation of ejaculation in the central nervous system and the related mechanisms.To establish the differential expression profiles of 5-HT2 B and its upstream proteins P2X7 and 5-HT in the central system.It was confirmed that sleep deprivation or sleep disturbance interfered with the regulation of ejaculation in rats by affecting the expression of 5-HT2 B,which in turn interfered with the regulation of ejaculation.Results: After sexual behavior training,rats were randomly assigned to three groups,followed by paradoxical sleep deprivation(SD)and subsequent restorative sleep(RS).The results indicated that intromission frequency(IF)was significantly lower in the PSD and RS groups compared to the control group,while IF was also significantly different in the PSD and RS groups.Compared with the CTRL group,mount frequency was reduced by 29.8%,intromission frequency by 21.7%,and ejaculation frequency by 34.9% in the RS group rats,suggesting that RS may partially reverse the effects of PSD on sexual behavior.After sleep deprivation,5-HT levels in hippocampal and raphe nucleus tissues of rats were significantly increased,while after 7 days of restorative sleep,5-HT concentrations were partially reduced,but still higher than those in control rats.After sleep deprivation,the expression levels of P2X7 receptor protein in hippocampus and raphe nucleus tissues of rats were significantly lower than those in restorative sleep and environmental control rats.The expression of 5-HT2 B receptors after sleep deprivation,on the other hand,showed the opposite trend to that of P2X7 receptors,and the expression level of 5-HT2 B receptor protein was significantly higher in the restorative sleep group and environmental control rats after sleep deprivation.Conclusion: Acute sleep deprivation for 96 hours impaired sexual behavior in male rats.After sleep deprivation,5-HT levels were significantly elevated in hippocampus and raphe nucleus tissues of rats.The P2X7 receptor and 5-HT2 B receptor had completely opposite trends after sleep deprivation,suggesting that these two receptors may be closely linked.Seven days of restorative sleep after sleep deprivation had a reversal effect on the changes of the above substances.Part Ⅲ: Investigation of sleep quality and related risk factors in patients with secondary premature ejaculationObjective: To determine the role of poor sleep quality as a risk factor for acquired premature ejaculation(APE)after considering the various risk factors,such as ages,lower urinary tract symptoms(LUTS),anxiety,depression,and erectile dysfunction.Methods: This study presents a multivariate analysis to identify risk factors for PE,including the covariate of age,International Prostate Symptom Score(IPSS),General Anxiety Disorder-7(GAD-7)score,Patient Health Questionnaire-9(PHQ-9)score,International Index of Erectile Function(ⅡEF)score,and Pittsburgh Sleep Quality Index(PSQI).Acquired PE was defined as self-reported intravaginal ejaculation latency time≤3 minutes,and poor sleep quality was diagnosed using the Pittsburgh Sleep Quality Index tool.Results: A total of 349 men were enrolled in the study after completing the questionnaires and the medical history survey.Among 349 men,203 individuals(58.17%)suffered from acquired PE.The ⅡEF-5 score,IPSS,GAD-7 score,PHQ-9 score,and PSQI score of the population with PE were significantly different from the non-PE group.Further multivariate analysis showed that erectile dysfunction,depression,severe prostatitis-like symptoms,and poor sleep quality were high-risk factors of APE.Additionally,our study showed that premature ejaculation diagnostic tool(PEDT)score was associated with IPSS/GAD-7/PHQ-9/PSQI scores positively and associated with ⅡEF-5 scores negatively.The stratified analysis of sleep quality showed that APE patients with different sleep qualities have different prevalence rates of anxiety,depression,prostatitislike symptoms,and erectile function.Conclusion: In general,sleep quality may be a potential risk factor for patients with acquired premature ejaculation.Our research revealed that the impact of sleep quality on premature ejaculation and provided new viewpoints for further understanding and perfecting the pathogenesis of premature ejaculation. |
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