Ka San Diego Bongaka ba Thobalano
LITLHAKISO TSE KHOLO TSE LING TSA BOPHELO
Taolo ea ts'ebetso ea thobalano ke tsamaiso ea methapo e kholo (CNS) e lula e sa utloisisoe hantle. Taolo ea penile erection e hlophisitsoe ka marang-rang a arohaneng a libaka tse ngata le tse hokahaneng kahare ho CNS le tsela tse ikhethang tsa methapo ea kutlo li lula li sa hlalosoe. Leha ho le joalo, khatelo-pele e se e entsoe ho khetholla likarolo tsa mantlha tse laolang karabelo ea botona kapa botšehali ho batona. Boithuto bo sebelisang positron emission tomography (PET) lithutong tsa banna tse phetseng hantle bo supile likarolo tse itseng tsa boko tse hlahisoang ho arabela molemong oa ho tsosa takatso ea botona kapa botšehali. Tsena li kenyelletsa "cortex" e tlase e tlase ea lefatše. libaka tse hokahantsoeng le setsoalle sa bonono, ts'ebetso ea tlhahisoleseling ea maikutlo le linaha tse susumetsang, le taolo ea mesebetsi ea autonomic le neuroendocrine.
Boithuto ba boithuto ba meetso ea liphoofolo bo ipakile bo le bohlokoa ho ts'ebetsong mekhoa e meng ea taolo e bohareng. Haholo-holo, ho ts'oha ha sebaka sa medial preoptic (MPOA) le "patventricular nucleus" (PVN) kahare ho hypothalamus ho tsebahala ho tsosa litsela tsa pro-erectile nerve ho litoeba. Likarolo tsena ka bobeli li sebetsa le ho kopanya leseli ho tsoa likarolong tse ngata tsa CNS, ho fumana maikutlo a tsoang ho pono (occipital), tactile (thalamus), le ho tsosa takatso (rhinencephalon) le ho kenyelletsa monahano. Maemo a ntseng a eketseha a dopamine le oxytocin a kopantsoe le ts'ebetso ea thobalano mme li-neurotransmitter tsena ho nahanoa hore li bapala likarolo tsa bohlokoa ho hanyetsanang karabelo ea pro-erectile ho MPOA le PVN, ka ho latellana.
Ka lehlakoreng le leng, nucleus paragigantocellularis (nPGi) bokong ba boko e fana ka phello e thibelang ho ho tsosa ha botona kapa botšehali. Metsoako e tlohang morerong oa nPGi ho isa likarolo tse fapaneng tsa lesapo la mokokotlo le serotonin e lokollang. Sena se phatlalalitsoe e le lebaka le etsang hore SSRI's (serotonin reuptake inhibitors) e nyenyefatse ts'ebetso ea thobalano. Ho khahlisang ke hore, kaha banna ba phekotsoeng ka lithethefatsi tsa SSRI hangata ba bonts'a ho lieha kapa ho koetsoe, linyeoe tsa kemolo pele ho nako le tsona li atlehile ka kalafo ea SSRI. Cousuleus ea locus le eona e kenyelletsa ntho e thibelang mahlo ka methapo e nang le kutloelo-bohloko e sebetsang le hypothalamic nuclei hammoho le mokokotlo oa lesapo la mokokotlo. Ho khaotsa ho kenyelletsa kutloelo-bohloko ka lebaka la ts'ebetso e hatelletsoeng ea locus coeruleus nakong ea REM (ho sisinyeha ha mahlo ka potlako) ho nahanoa hore e lebisa ho liketsahalo tsa bosiu tsa boteng ba penile.
Boithuto bo eketsehileng ba anatomical le bo sebetsang bo lokela ho eketsa kutloisiso ea rona ea potoloho ea neural ka har'a CNS e laolang penile erection. Ho hlalosa likarolo tsa li-neurotransmitters ho tsoela pele e le mosebetsi o rarahaneng, hobane ka nepo li ka hlahisa litlamorao tse fapaneng ho latela sebaka sa ts'ebetso le kabo ea "receptor" subtype ka likarolo tse ikhethileng tsa neuronal.
Mekhoa ea PERIPHERAL METSOALLE EA SEXUAL ArOUSAL
Molao oa Neurogenic oa Penile Erection
Ts'ebetso ea Erectile ka botoneng e laoloa ke autonomic (parasympathetic le kutloelo-bohloko) le tsela ea methapo (sensory le motor) ho ea ho li-tishu tsa erectile le mesifa e pheresehang. Likarolo tse tharo tsa methapo ea kutlo e ka hare ho setho sa botona.
Metsing e nang le kutloelo-bohloko (T10-L2), e ikarabellang bakeng sa ho senyeha ha matla le ho boloka ho fifala, projeke ho koporasi, hammoho le prostate le molala oa senya ka methapo ea hypogastric. Likhoele tsa Postganglionic noradrenergic li fetisetsa kamora 'mele ho prostate ho seo ho thoeng ke methapo ea Walsh ho kena ho corpora cavernosa nakong e bohareng. Molumo oa li-adrenergic o bohlokoa ho qaleng ho itšireletsa le ho boloka boemo ba botona bo le bobebe ho tloha ha mesifa e boreleli ea methapo le cavernosal trabeculae e tlameha ho lula e le tumellano ka mafolofolo. Khutsufatso ea cavernosal trabecular boreleli ea mesifa ho norepinephrine e buelloa ke alpha-1 adrenergic receptors. Pre-junctional alpha-2 adrenergic receptors on adrenergic methapo e thibela ho tsamaisoa ha methapo ea kutlo le ho fana ka maikutlo a itlhophisang a maikutlo a fosahetseng bakeng sa norepinephrine e patiloeng. Metsing ea Cholinergic e sebetsana le li-receptor tsa muscinic pele ho junctional hape e thibela tšebetso ea methapo ea adrenergic.
Ho ka etsahala hore ho leka-lekana ha adrenergic mabapi le vasoconstriction impairs erection. Le ha lintlha tse ikhethileng tse bakang ho se leka-lekane hona li lula li sa tsejoe, ho tsofala le / kapa linaha tse amanang le lefu li ka baka boikhethelo ba ho khetha litlatsetso tse khethehileng tsa adrenergic receptor subtypes, tsa etsa hore ts'ebetso e phahameng ea ts'ebetso ea norepinephrine e sebetse. Kaha norepinephrine ke module ea bohlokoa ea ts'ebetso ea erectile, hoa utloahala hore bahanyetsi ba alpha-adrenergic receptor ba ka ipaka ba le molemo kalafong ea ED. Boiphihlelo ba tleliniking le lithethefatsi tse kang yohimbine le phentolamine bo bontšitse katleho e fapaneng ho banna ba nang le ED. Karolo ea li-receptor tsa alpha-adrenergic ho physiology ea penile erection e hlahlojoa ka botlalo libakeng tse ling.
Metsing ea parasympathetic, e tsoang mokokotlong oa lipakeng tsa S2-S4 mokokotlo oa mokokotlo, e fana ka tšusumetso e kholo ho botoneng mme e ikarabella bakeng sa vasodilation ea penile vasculature le ho emisoa kamora moo. Ha li tsoa ka har'a sacral foramina, methapo ena e fetela ka lehlakoreng le leng e le methapo ea pelvic le synapse plexus ea pelvic e nang le likhoele tsa post-ganglionic nonadrenergic, noncholinergic (NANC), tse tsamaeang kahare ho methapo ea cavernous ho ea corpora cavernosa. Vasoactive intestinal peptide (VIP) le nitric oxide (NO) ke li-neurotransmitters tse peli tsa NANC tse atisang ho kopanngoa le methapo e tšoanang ea lisele tsa penile. Leha ho le joalo, karolo ea VIP e le modulator ea penile erection e ntse e sa hlaka kaha liphetho tsa liteko tsa peptide ena ea ts'ebetso ea erectile ha li lumellane. Tsamaiso ea Intracavernosal ea VIP liphoofolong le bathong e hlahisitse liphetho tse fapaneng, ho tloha ho se na phello ho isa ho tumescence e sa fellang ho fihlela erection e felletseng. Ho feta moo, khaello ea bahanyetsi ba ikhethileng le ba sebetsang bakeng sa VIP e sitisa lipatlisiso tsa liteko mabapi le karolo ea eona mosebetsing oa erectile.
Mokena-lipakeng oa mantlha oa tlatsetso ea NANC parasympathetic ke NO. Bokhoni ba NO, e leng khase e sa sebetseng hantle le e sa tsitsang, ho laola likarolo tse fapaneng tsa ts'ebetso ea mmele ho liphoofolo tse anyesang e bonahetse feela lilemong tse mashome a mabeli tse fetileng. Hammoho le carbon monoxide, NO ke molek'hule e ikhethileng ea tšebetso ea mantlha e nang le litšobotsi tsa len messengerosa la bobeli la lisele tse hlomphollang merero ea pejana. Ho hlakile hore e hlophisitsoe ka tlhokeho e nang le polokelo e nyane kapa e se na eona ka kotloloho ebe e kenya enzyme e qhibilihang ka kotloloho (guanylate cyclase) ho fapana le molek'hule ea "setso" ea mokelikeli. NO e hlahisoa ke nitric oxide synthase (NOS) e sebelisang amino acid L-arginine le oksijene ea limolek'hule e le likaroloana ho hlahisa NO le L-citrulline. HA HO motho ea ka tšelang habonolo lera la lero la mali ho kena liseleng tse shebiloeng moo e tlamang karolo ea heme ea guanylate cyclase e qhibilihang. Ts'ebetso ena ea guanylate cyclase e hlohlelletsa tlhahiso ea cGMP ka ts'ebeliso ea sephetho sa cGMP e itšetlehileng ka protein kinase e laolang liketsahalo tsa lisele tse lebisang ho phomoleng ha mesifa e boreleli. Methati ea cGMP le eona e laoloa ke phosphodiesterases, e senyang cGMP ebe e emisa ho saena. Sildenafil (Viagra), tadalafil (Cialis) le vardenafil (Levitra) ke li-inhibitors tse matla, tse khethiloeng le tse ka feto-fetohang tsa mofuta oa 2, enzyme e kholo e ikarabellang bakeng sa cGMP hydrolysis ka lisele tsa penile erectile. Thibelo ea enzyme ena e lebisa keketsehong ea li-intracellular cGMP le ntlafatso ea boikhathollo ba mesifa e boreleli ho arabela tšusumetso e sebelisang tsela ea NO / cGMP. Ketsahalo e joalo e ka hlalosa ts'ebeliso e atlehileng ea baemeli bana kalafong ea banna ED.
Haufinyane, ho bonahetse hore HA ho na motho ea ikopanyetsang ka kotloloho le merero e meng ea selefounu ho kenyelletsa li-receptor, liteishene tsa ion le lipompo, tse ka fetolang botsitso ba cell cell contract, bo ikemetseng tseleng ea cGMP. Kahoo, ho tlatselletsa ho cyclase ea guanylate, NO e na le lipheo tse ling tse ka hare, tse ka bapalang taolo ea tumellano ea mesifa le ea trabecular boreleli.
Ts'ebetso ea methapo ea kutlo ea NANC e kanna ea fetoloa ke methapo ea cholinergic, e thusang boikhathollo ba nonadrenergic, noncholinergic ka ho tsosa motsoako le tokollo ea NO le li-neurotransmitters tse ling tsa vasodilatory tse kang VIP. Ka hona, ho lokolloa ha acetylcholine ho ka tsamaisa ho tlosoa ha karabelo ea adrenergic le keketseho ea karolo ea NANC ka ho tlama ho li-receptor tsa pre-jemental muscarinic ho li-nerve tsa adrenergic le NANC. Maemong a itseng a maloetse a kang lefu la tsoekere, bokhoni ba corpus cavernosum ba ho kopanya le ho lokolla acetylcholine bo fokotsehile. Ts'ebetso tse joalo li kanna tsa ikarabella ho karolo ea ts'ebetso ea erectile e amanang le lefu la tsoekere. Litla-morao tsa Parasympathetic le tsona li hlaseleha habonolo nakong ea ts'ebetso ea ts'ebetso ea bongaka, e kang ho saroloha ha mpa ka mpeng ea rectum le radatitisomy ea radical.
Manonyeletso a pudendal a kenyelletsa likhoele tse tsamaisang mokokotlo le tse tsamaisang methapo e ka hare ea mesifa ea ischiocavernous le bulbocavernous hammoho le letlalo la penile le letlalo. Litopo tsa lisele tsa Pudendal motor neuron li sebakeng sa Onuf bokong ba likarolo tsa S2-S4. Mofuta oa pudendal o kenella ka har'a perineum ka "notch" e tlase haholo kamoreng e ka morao ea mochine oa ischiorectal fossa 'me e tsamaea ka canal ea "Alcock" (pudendal canal) e lebisang karolong e ka morao ea membrane ea perineal. Mothating ona, e hlahisa mokokotlo oa mokokotlo o nang le makala ho ea ho scrotum le mokokotlo oa mokokotlo o fanang ka sebaka se tlaase sa rectal. Leqhubu la dorsal la botoneng le hlaha e le lekala la ho qetela la mokokotlo oa pudendal. E ntan'o retelehela ka thoko ho shaft ea dorsal penile, hamorao e leba mokokotlong oa dorsal. Li-fascicles tse ngata li atoloha hole, li fana ka mafelo a methapo ea kutlo le a methapo ea kutlo methapong ea "tulica albuginea" le letlalo la moqomo oa penile le glans penis.
Li-modulators tse se nang neuronal tsa Penile Erection
Ntle le methapo ea neurogenic, ho bonahetse hore lintlha tsa lehae tsa paracrine / autocrine, hammoho le litlamorao tse mpe le / kapa li-trophic, li ka susumetsa ka matla ts'ebetso ea mesifa e boreleli ka botoneng. Tsena li kenyelletsa endothelin, prostanoids, nitric oxide le oksijene.
Endothelin-1 (ET-1), setho sa lelapa la endothelin la li-peptide, ke e 'ngoe ea li-vasoconstrictor tse matla ka ho fetesisa tse hlalositsoeng. Ka mokhoa o ts'oanang le nitric oxide, endothelin e lokolloa kahare ea likarolo tsa methapo ea methapo e ka susumetsoa ke khatello ea maikutlo. Leha ho le joalo, ha ho tsejoe hanyane ka mmele le lisele tse laolang tlhahiso ea tsona. Ho corpus cavernosum ea motho, ET-1 e hlophisitsoe ke endothelium mme e fana ka likhohlano tse matla, tse tšoarellang tsa corpus cavernosum boreleli ba mesifa. Li-subtypes tse kholo tsa endothelin receptors (ETA le ETB) li fumanoe ka penile corpus cavernosum mme li ajoa ho endothelium le mesifa e boreleli. Ho boetse ho fanoe ka tlhahiso ea hore endothelin e kanna ea hlahisa litlamorao tsa methapo ea kutlo ka mokhoa o tlase oa "kamano e phahameng" ea mokelikeli oa ETB, mohlomong ka ho hlasimolla tlhahiso ea NO. Leha ho le joalo, bohlokoa ba mochini ona ka penile erection bo ntse bo sa hlaka. Mefuteng ea mafu a mebutlanyana, li-receptor tsa ETB ka penile corpus cavernosum li ne li laoloa holimo ho mebutlanyana e bakoang ke lefu la tsoekere 'me e laoloa tlase ho mebutlanyana ea Watanabe ea hypercholesterolemic. Ntle le moo, maemo a phahameng a endothelin a plasma a tlalehiloe ho banna ba nang le lefu la tsoekere le bao e seng ba nang le lefu la tsoekere ba nang le ho se sebetse ha erectile. Kahoo, endothelin e ka kenya letsoho tlhokomelong ea penile flaccidity ka ho fana ka molumo o tsitsitseng ho mesifa e boreleli 'me liphetoho tse hlahisoang ke endothelin li ka baka tšebetso e mpe ea erectile. Ho hlahisitsoe bahanyetsi ba 'maloa ba khethiloeng ba endothelin receptor subtype, empa ts'ebetso ea bona le polokeho kalafong ea ED ha e so hlahlojoe ka botlalo.
Ntle le methapo ea NANC, vasotine endothelium e sebetsa ebile e ntsha nitric oxide. Li-Vasodilator tse kang acetylcholine le bradykinin li sebetsa ka ho tlama li-receptor tsa tsona tsa membrane le ho eketsa li-Ca2 tse kenang ka hare ho lisele tsa endothelial. Tlhahlobo ea 'mele, joalo ka khatello ea shear, e boetse e tsejoa ho ntlafatsa tlhahiso ea NO ho endothelium. Boemong ba botoneng, tlhahiso ea ha-NO e hlahisoang ke endothelium e ka etsahala hangata haholo nakong ea kemaro ha mali a kena ka har'a 'mele ea phofo ea mpa e eketseha ka potlako. Mokhoa oa ketso ea endothelium-based NO o tšoana le nerve e nkiloeng ka nerve, joalo ka ha ho hlalositsoe karolong e fetileng.
Prostanoids (eicosanoids, prostaglandins) ke lintho tse tsoang ho tse ling tse mashome a mabeli tse hlahisitsoeng ke ketso ea cycloo oxygenase ho "precachor arachidonic acid" e teng habeli liseleng tsa mesifa tse bonolo tsa "corpora cavernosa". Li-Prostanoids li sebetsa sebakeng sa heno mme li hlahisa litlamorao le liphatlalatso ka bobeli ka tsela e ikemetseng. Le ha karolo e nepahetseng ea 'mele ea li-prostaglandins ho li-penile erection e sa hlalosehe hantle, bopaki ba liteko bo bontša hore li ka bapala karolo ea bohlokoa taolong ea tlhahiso ea matrix ea extracellular. Ho feta moo, litlamorao tsa anti-platelet tse kopanyang tsa PGI2 (prostacyclin), tse ts'oanang le NO, li ka ba tsa bohlokoa ho thibela ho tsibana ha mali, kaha phallo ea mali ka har'a 'mele ea cavernosal e sa tsotellehe nakong ea ho ruruha ho hoholo ha penile. Lithako tse hlano tse sebetsang tsa "prostanoid" kahare botoneng ke li-prostaglandins PGD2, PGE2, PGF2?, PGI2 le thromboxane A2 (TXA2). Li-Prostanoids li ka khatholla boikhathollo le boqhekanyetsi ho penile Corpus cavernosum. PGE ke eona feela "prostaglandin" ea tlhaho e shebahalang e khatholla mesifa ea boreleli ea trabecular; ba bang ba baka constriction kapa ba se na phello ea molumo o bonolo oa mesifa. Ho na le lihlopha tse hlano tse kholo tsa li-receptor tsa "prostanoid" tse bitsoang DP, EP, FP, IP le TP, tse arabelang litlamorao tsa PGD, PGE, PGF, PGI le thromboxane, ka ho latellana. Litlamorao tse sebetsang ka bongata, tse itšetlehileng ka litekanyetso tsa li-prostanoid li ka hlalosoa ka ho kopanya li-subtypes tsa li-receptor le li-isoforms ho li-system tse fapaneng tsa len messengerosa la bobeli. Ka karolelano, prostaglandin E1 (alprostadil) e se e hlahisitsoe e le FDA ea pele e amohetseng lithethefatsi tse kenang tsa entracavernosal bakeng sa kalafo ea banna ba batona.
Ho tsitsipana ha oksijene ho bapala karolo ea bohlokoa ho laoleng qoqotho ea penile. Litekanyo tsa mali a cavernosal PO2 lithutong tsa baithaopi ba motho li bontša hore likhohlano tsa oksijene li fetoha ka potlako ho tloha li-venous (~ 35 mm Hg) ho ea maemong a arterial (~ 100 mm Hg) nakong ea phetoho ho tloha ho flaccid ho ea naheng e otlolohileng. Ho boloka tsitsipano ea oksijene ke ntho ea bohlokoahali liseleng tse ngata tsa mmele empa botona ke eona feela setho, se fetohang ho tsitsipano ea oksijene nakong ea ts'ebetso ea eona e tloaelehileng. Phetoho ena ke motheo oa mokhoa o ikhethileng oa taolo o sebelisang monyetla oa li-enzyme tsa bohlokoa tsa maiketsetso, tse sebelisang oksijene ea limolek'hule e le karolo e kopanetsoeng. NO NO synthase le prostaglandin synthase ke mehlala e 'meli e ithutoang hantle ea sehlopha sa li-enzyme tse tsejoang e le dio oxygenase. Ka khatello ea moea o tlase, e lekantsoeng sebakeng se botona ba botoneng, motsoako oa NO ha oa thibeloa, o thibela ho phomola hoa mesifa ea trabecular. Thibelo ena ea NO ea tlhahiso e kanna ea hlokahala bakeng sa ho boloka penile flaccidity. Ka mor'a vasodilation ea methapo ea methapo, ho eketseha ha methapo ea methapo ho tsosa moea oa moea. Tikolohong e ntlafalitsoeng ea oksijene, methapo ea methapo ea kutlo le endothelium li khona ho kopanya NO, mediation trabecular boreleli ea mesifa. Mokhoa oa ho sebetsa oa li-prostanoid ka mokhoa o ts'oanang o laoloa ka mokhoa o hlakileng har'a maemo a mabe. Ka hona, tsitsipano ea oksijene e ka laola mefuta ea lintho tse mpe tse teng betheng ena ea methapo. Ka tsitsipano e tlase ea oksijene, ho thatafala ha norepinephrine le endothelin ho ka mpefala, ha ho ba le tsitsipano e phahameng ea oksijene, NO le li-prostaglandins li hlahisoa ka lebaka la ho fumaneha ha oksijene ea molek'hule e hlokahalang bakeng sa motsoako oa eona.
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