肠道菌群–大麻素系统与早泄的研究进展
Advances in the Study of Intestinal Flora-Cannabinoid System and Premature Ejaculation
摘要: 早泄是常见的性功能障碍疾病之一，选择性5-羟色胺再摄取抑制剂因提高5-羟色胺(5-hydroxytryptamine, 5-HT)浓度在治疗抑郁症时能有效延长射精潜伏时间。目前的研究指出大麻素系统与5-HT系统在功能上相互影响且相互依赖。肠道菌群能够调节机体代谢组成并以5-HT为介导最终影响个体情绪与应激，通过益生菌治疗能有效逆转肠道菌群的情绪反应。本文基于肠道菌群及大麻素系统，深入探讨肠道菌群与早泄疾病发生及治疗上的相关性。
Abstract: Premature ejaculation is one of the common sexual dysfunction diseases. Selective serotonin reuptake inhibitors can effectively prolong ejaculation latency in the treatment of depression by increasing the concentration of 5-HT. Current research points to the functional interaction and in-terdependence of the cannabinoid system and the 5-HT system. Intestinal flora can regulate the body’s metabolic composition and ultimately affect individual mood and stress through 5-HT. Pro-biotic treatment can effectively reverse the emotional response of gut flora. Based on the gut micro-biota and cannabinoid system, this paper deeply explores the correlation between the gut microbi-ota and the occurrence and treatment of premature ejaculation.
文章引用：郑俊, 张俊勇, 张唯力. 肠道菌群–大麻素系统与早泄的研究进展[J]. 临床医学进展, 2022, 12(9): 8330-8336. https://doi.org/10.12677/ACM.2022.1291200

参考文献

[1] 袁亦铭, 辛钟成. 射精功能神经调节机制研究进展[J]. 中国男科学杂志, 2004, 18(6): 54-57.
[2] 闫向前, 等. 伊木萨克片联合盐酸达泊西汀治疗原发性早泄的临床观察[J]. 中华男科学杂志, 2016(9): 817-822.
[3] Lach, G., et al. (2018) Anxiety, Depression, and the Microbiome: A Role for Gut Peptides. Neurotherapeutics, 15, 36-59. [Google Scholar] [CrossRef] [PubMed]
[4] Byers, E.S. and Grenier, G. (2003) Premature or Rapid Ejacula-tion: Heterosexual Couples’ Perceptions of Men’s Ejaculatory Behavior. Archives of Sexual Behavior, 32, 261-270. [Google Scholar] [CrossRef] 
[5] Carson, C. and Gunn, K. (2006) Premature Ejaculation: Definition and Prevalence. International Journal of Impotence Research, 18, S5-S13.
[6] Xu, C., et al. (2006) Identification of Lumbar Spinal Neurons Controlling Simultaneously the Prostate and the Bulbospongiosus Muscles in the Rat. Neuro-science, 138, 561-573. [Google Scholar] [CrossRef] [PubMed]
[7] Egashira, N., et al. (2006) In-volvement of 5-hydroxytryptamine1A Receptors in Delta9-Tetrahydrocannabinol-Induced Catalepsy-Like Immobilization in Mice. European Journal of Pharmacology, 550, 117-122. [Google Scholar] [CrossRef] [PubMed]
[8] Murillo-Rodríguez, E., et al. (2008) The Anandamide Membrane Transporter Inhibitor, VDM-11, Modulates Sleep and c-Fos Expression in the Rat Brain. Neuroscience, 157, 1-11. [Google Scholar] [CrossRef] [PubMed]
[9] Ward, S.J., et al. (2008) Effects of a Cannabinoid1 Recep-tor Antagonist and Serotonin2C Receptor Agonist Alone and in Combination on Motivation for Palatable Food: A Dose-Addition Analysis Study in Mice. Journal of Pharmacology & Experimental Therapeutics, 325, 567-576. [Google Scholar] [CrossRef] [PubMed]
[10] Marco, E.M., et al. (2005) Involvement of 5-HT1A Receptors in Be-havioural Effects of the Cannabinoid Receptor Agonist CP 55,940 in Male Rats. Behavioural Pharmacology, 15, 21-27. [Google Scholar] [CrossRef] [PubMed]
[11] Simpson, C.A., et al. (2021) The Gut Microbiota in Anxiety and Depression—A Systematic Review. Clinical Psychology Review, 83, Article ID: 101943. [Google Scholar] [CrossRef] [PubMed]
[12] 肖福兴, 王福才, 谢赞兵. 达泊西汀治疗早泄的临床研究[J]. 皮肤病与性病, 2018, 40(3): 456-457.
[13] Viveka, et al. (1998) Facilitation and Inhibition of Male Rat Ejaculatory Be-haviour by the Respective 5-HT1A and 5-HT1B Receptor Agonists 8-OH-DPAT and Anpirtoline, as Evidenced by Use of the Corresponding New and Selective Receptor Antagonists NAD-299 and NAS-181. British Journal of Pharmacol-ogy, 125, 1733-1743.
[14] Wolters, J.P. and Hellstrom, W.J. (2006) Current Concepts in Ejaculatory Dysfunction. Re-views in Urology, 8, S18-S25.
[15] Olivier, B., van Oorschot, R. and Waldinger, M.D. (1998) Serotonin, Serotonergic Receptors, Selective Serotonin Reuptake Inhibitors and Sexual Behaviour. International Clinical Psychopharmacology, 13, S9-S14. [Google Scholar] [CrossRef] [PubMed]
[16] Waldinger, M.D., et al. (1998) Familial Occurrence of Primary Premature Ejaculation. Psychiatric Genetics, 8, 37-40. [Google Scholar] [CrossRef] [PubMed]
[17] 杨德威. 原发性早泄与5-HT系统基因多态性相关性的研究进展[J]. 中华男科学杂志, 2021, 27(8): 748-752.
[18] Bradley, S.L., et al. (2005) Relationship of Serotonin Transporter Gene Polymorphisms and Haplotypes to mRNA Transcription. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 136, 58-61. [Google Scholar] [CrossRef] [PubMed]
[19] Roaiah, M.F., et al. (2019) 5HT-1A Receptor Polymorphism Effects Ejaculatory Function in Egyptian Patients with Lifelong Premature Ejaculation. Revista Internacional de Andrología, 17, 138-142. [Google Scholar] [CrossRef] [PubMed]
[20] Janssen, P.K., et al. (2014) The 5-HT1A Receptor C(1019)G Polymorphism Influences the Intravaginal Ejaculation Latency Time in Dutch Caucasian Men with Lifelong Premature Ejaculation. Pharmacology Biochemistry and Behavior, 121, 184-188. [Google Scholar] [CrossRef] [PubMed]
[21] Jern, P., et al. (2012) A Study of Possible Associations between Single Nucleotide Polymorphisms in the Serotonin Receptor 1A, 1B, and 2C Genes and Self-Reported Ejaculation La-tency Time. The Journal of Sexual Medicine, 9, 866-872. [Google Scholar] [CrossRef] [PubMed]
[22] Waldinger, M.D., et al. (1998) Premature Ejaculation and Serotonergic Antidepressants-Induced Delayed Ejaculation: The Involvement of the Serotonergic System. Behavioural Brain Research, 92, 111-118. [Google Scholar] [CrossRef] 
[23] Waldinger, M.D., Schweitzer, D.H. and Olivier, B. (2005) On-Demand SSRI Treatment of Premature Ejaculation: Pharmacodynamic Limitations for Relevant Ejaculation Delay and Consequent Solutions. The Journal of Sexual Medicine, 2, 121-131. [Google Scholar] [CrossRef] [PubMed]
[24] Bagdy, G., et al. (2001) Anxiety-Like Effects Induced by Acute Fluoxetine, Sertraline or m-CPP Treatment Are Reversed by Pretreatment with the 5-HT2C Receptor Antagonist SB-242084 but Not the 5-HT1A Receptor Antagonist WAY-100635. International Journal of Neuropsychopharmacol-ogy, 4, 399-408. [Google Scholar] [CrossRef] 
[25] Kantor, S., et al. (2001) Rapid Desensitization of 5-HT(1A) Re-ceptors in Fawn-Hooded Rats after Chronic Fluoxetine Treatment. European Neuropsychopharmacology, 11, 15-24. [Google Scholar] [CrossRef] 
[26] Dekeyne, A., et al. (2000) Citalopram Reduces Social Inter-action in Rats by Activation of Serotonin (5-HT)2C Receptors. Neuropharmacology, 39, 1114-1117. [Google Scholar] [CrossRef] 
[27] Lazary, J., et al. (2009) Promoter Variants of the Canna-binoid Receptor 1 Gene (CNR1) in Interaction with 5-HTTLPR Affect the Anxious Phenotype. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 150, 1118-1127. [Google Scholar] [CrossRef] [PubMed]
[28] 张永超. 5-羟色胺受体与抑郁症相关性的研究进展[J]. 医学综述, 2014, 20(5): 772-775.
[29] Colangeli, R., Teskey, G.C. and Di Giovanni, G. (2021) Endocannabinoid-Serotonin Systems Interaction in Health and Disease. Progress in Brain Research, 259, 83-134. [Google Scholar] [CrossRef] [PubMed]
[30] Lazary, J., et al. (2011) Personalized Medicine Can Pave the Way for the Safe Use of CB1 Receptor Antagonists. Trends in Pharmacological Sciences, 32, 270-280. [Google Scholar] [CrossRef] [PubMed]
[31] Freund, T.F., Katona, I. and Piomelli, D. (2003) Role of Endogenous Cannabinoids in Synaptic Signaling. Physiological Reviews, 83, 1017-1066. [Google Scholar] [CrossRef] [PubMed]
[32] Szabo, B. and Schlicker, E. (2005) Effects of Cannabinoids on Neurotransmission. Handbook of Experimental Pharmacology, Vol. 168, Springer, Berlin, 327-365. [Google Scholar] [CrossRef] [PubMed]
[33] Pacher, P., Bátkai, S. and Kunos, G. (2006) The Endocannabinoid System as an Emerging Target of Pharmacotherapy. Pharmacological Reviews, 58, 389-462. [Google Scholar] [CrossRef] [PubMed]
[34] Egertová, M., et al. (1998) A New Perspective on Cannabinoid Signalling: Complementary Localization of Fatty Acid Amide Hydrolase and the CB1 Receptor in Rat Brain. Proceedings: Biological Sciences, 265, 2081-2085. [Google Scholar] [CrossRef] [PubMed]
[35] Moldrich, G. and Wenger, T. (2000) Localization of the CB1 Canna-binoid Receptor in the Rat Brain. An Immunohistochemical Study. Peptides, 21, 1735-1742. [Google Scholar] [CrossRef] 
[36] Nawata, Y., et al. (2019) Inhibition of Monoacylglycerol Li-pase Reduces the Reinstatement of Methamphetamine-Seeking and Anxiety-Like Behaviors in Methamphetamine Self-Administered Rats. International Journal of Neuropsychopharmacology, 22, 165-172. [Google Scholar] [CrossRef] [PubMed]
[37] Haj-Dahmane, S. and Shen, R.Y. (2005) The Wake-Promoting Peptide Orexin-B Inhibits Glutamatergic Transmission to Dorsal Raphe Nucleus Serotonin Neurons through Retrograde Endo-cannabinoid Signaling. Journal of Neuroscience, 25, 896-905. [Google Scholar] [CrossRef] 
[38] Haj-Dahmane, S. and Shen, R.Y. (2009) Endocanna-binoids Suppress Excitatory Synaptic Transmission to Dorsal Raphe Serotonin Neurons through the Activation of Pre-synaptic CB1 Receptors. Journal of Pharmacology and Experimental Therapeutics, 331, 186-196. [Google Scholar] [CrossRef] [PubMed]
[39] Tao, R. and Ma, Z. (2012) Neural Circuit in the Dorsal Raphe Nucle-us Responsible for Cannabinoid-Mediated Increases in 5-HT Efflux in the Nucleus Accumbens of the Rat Brain. ISRN Pharmacology, 2012, Article ID: 276902. [Google Scholar] [CrossRef] [PubMed]
[40] Moranta, D., Esteban, S. and García-Sevilla, J.A. (2004) Differential Ef-fects of Acute Cannabinoid Drug Treatment, Mediated by CB1 Receptors, on the in Vivo Activity of Tyrosine and Tryp-tophan Hydroxylase in the Rat Brain. Naunyn-Schmiedeberg’s Archives of Pharmacology, 369, 516-524. [Google Scholar] [CrossRef] [PubMed]
[41] Nakazi, M., et al. (2000) Inhibition of Serotonin Release in the Mouse Brain via Presynaptic Cannabinoid CB1 Receptors. Naunyn-Schmiedeberg’s Archives of Pharmacology, 361, 19-24. [Google Scholar] [CrossRef] [PubMed]
[42] Sheline, Y.I., et al. (1996) Hippocampal Atrophy in Recurrent Major Depression. Proceedings of the National Academy of Sciences of the United States of America, 93, 3908-3913. [Google Scholar] [CrossRef] [PubMed]
[43] Chevalier, G., et al. (2020) Effect of Gut Microbiota on Depres-sive-Like Behaviors in Mice Is Mediated by the Endocannabinoid System. Nature Communications, 11, Article No. 6363. [Google Scholar] [CrossRef] [PubMed]
[44] Yang, C., et al. (2017) Bifidobacterium in the Gut Microbiota Confer Resilience to Chronic Social Defeat Stress in Mice. Scientific Reports, 7, Article No. 45942. [Google Scholar] [CrossRef] [PubMed]
[45] Dinan, T.G. and Cryan, J.F. (2013) Melancholic Microbes: A Link between Gut Microbiota and Depression? Neurogastroenterology & Motility, 25, 713-719. [Google Scholar] [CrossRef] [PubMed]
[46] Cani, P.D., et al. (2016) Endocannabinoids—At the Crossroads between the Gut Microbiota and Host Metabolism. Nature Reviews Endocrinology, 12, 133-143. [Google Scholar] [CrossRef] [PubMed]
[47] Möhle, L., et al. (2016) Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis. Cell Reports, 15, 1945-1956. [Google Scholar] [CrossRef] [PubMed]

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