RhoA-PKA通路调控H2S开放大鼠海马神经元BKCa通道和抗神经元H-R损伤及内皮源性H2S对该通道的影响

RhoA-PKA通路调控H2S开放大鼠海马神经元BKCa通道和抗神经元H-R损伤及内皮源性H2S对该通道的影响摘要：本研究旨在探究RhoA-PKA信号通路对H2S开放大鼠海马神经元BKCa通道的调节作用以及抗神经元H/R损伤与内皮源性H2S对该通道的影响。实验分为三组：对照组、模拟细胞缺氧/复氧组和内皮细胞培养液预处理组。结果表明，H2S处理能够促进海马神经元BKCa通道的开放，提高神经元的电活性，这种效果与RhoA-PKA信号通路密切相关。同时，在H/R损伤模型下，H2S对神经元的保护作用也可能与该通路的调节有关。内皮细胞培养液预处理可以改善H/R损伤对神经元BKCa通道造成的影响，而这种效果主要是通过提高内皮源性H2S水平来实现的。综上所述，RhoA-PKA信号通路在调节H2S开放大鼠海马神经元BKCa通道中扮演着重要角色，而内皮源性H2S对此通道的身体保护作用也值得进一步研究。

关键词：RhoA-PKA通路，H2S，神经元，BKCa通道，H/R损伤，内皮源性H2S

Abstract:ThepresentstudywasdesignedtoinvestigatetheregulationofRhoA-PKAsignalingpathwayonH2S-inducedopeningofBKCachannelsinrathippocampalneuronsaswellastheeffectofanti-neuronalH/RinjuryandendogenousH2Sonsuchchannels.Theexperimentwasdividedintothreegroups:controlgroup,simulatedcellhypoxia/reoxygenationgroup,andendothelialcellculturemediumpretreatmentgroup.TheresultsshowedthatH2StreatmentcouldpromotetheopeningofhippocampalneuronBKCachannelsandenhanceneuronalexcitability,whichwascloselyrelatedtotheRhoA-PKAsignalingpathway.Meanwhile,theprotectiveeffectofH2SonneuronsintheH/Rinjurymodelmightalsoberelatedtotheregulationofthispathway.PretreatmentwithendothelialcellculturemediumcouldimprovetheeffectofH/RinjuryontheBKCachannelsofneurons,andthiseffectwasmainlyachievedbyincreasingthelevelofendogenousH2S.Inconclusion,theRhoA-PKAsignalingpathwayplaysanimportantroleinregulatingtheopeningofBKCachannelsinrathippocampalneuronsinducedbyH2S,andthebody-protectiveeffectofendogenousH2Sonthesechannelsdeservesfurtherstudies.

Keywords:RhoA-PKAsignalingpathway,H2S,neuron,BKCachannels,H/Rinjury,endogenousH2SInrecentyears,thediscoveryofthephysiologicalandpathologicalfunctionsofH2Shasattractedalotofattention.IthasbeenfoundthatH2Splaysanimportantroleintheregulationofvariousphysiologicalprocesses,includinginflammation,oxidativestress,andcellmetabolism.However,theunderlyingmechanismsofH2Sactionsarenotwellunderstood.

Inthisstudy,weinvestigatedtheeffectofH2SontheopeningofBKCachannelsinrathippocampalneuronsinducedbyH/Rinjury.WefoundthatH2ScouldsignificantlyenhancetheopeningofBKCachannelsintheseneurons,andthiseffectwasmainlymediatedbytheRhoA-PKAsignalingpathway.

TheRhoA-PKAsignalingpathwayisawell-knownpathwayinvolvedintheregulationofvariouscellularprocesses,includingneuronalexcitationandsynapticplasticity.OurresultsshowedthatH2ScouldactivatethispathwayandenhancetheopeningofBKCachannelsinrathippocampalneurons.Moreover,inhibitingthispathwaycouldabolishtheeffectofH2SonBKCachannels,suggestingthattheRhoA-PKAsignalingpathwayiscriticalfortheH2S-inducedopeningofBKCachannels.

Furthermore,wefoundthatendogenousH2ScouldalsoenhancetheopeningofBKCachannelsandprotectneuronsfromH/Rinjury.Thissuggeststhatthebody'sendogenousH2SlevelsmayplayaroleinregulatingtheopeningofBKCachannelsandprotectingneuronsfrominjury.

Inconclusion,ourstudyprovidesnewinsightsintotheunderlyingmechanismsofH2Sactionsinneurons.TheRhoA-PKAsignalingpathwayplaysanimportantroleinregulatingtheopeningofBKCachannelsinrathippocampalneuronsinducedbyH2S,andthebody-protectiveeffectofendogenousH2SonthesechannelsdeservesfurtherstudiesMoreover,ourfindingssuggestthatH2Scouldpotentiallybeusedasatherapeuticagenttoprotectagainstneuronaldamageorinjury.ThereisgrowingevidencethatH2Shasawiderangeofbiologicalactivities,includinganti-inflammatory,antioxidant,andneuroprotectiveeffects.Assuch,H2Sdonorshavebeenproposedaspotentialtreatmentsforvariousneurologicaldisorders,suchasAlzheimer'sdisease,Parkinson'sdisease,andstroke.

However,therearestillmanyunansweredquestionsregardingthepotentialtherapeuticuseofH2S.Forexample,theoptimaldoseanddurationofH2Streatment,aswellaspotentialsideeffects,needtobefurtherstudied.Additionally,thecellularandmolecularmechanismsunderlyingH2S-mediatedneuroprotectionrequirefurtherinvestigation.

Overall,ourstudycontributestoabetterunderstandingofthecomplexrolesthatH2Splaysinneuronalphysiologyandhighlightsthepotentialtherapeuticapplicationsofthismoleculeinthetreatmentofneurologicaldisorders.FutureresearchinthisfieldmayleadtothedevelopmentofsaferandmoreeffectivetreatmentsforthesedevastatingconditionsAlongwithitspotentialneuroprotectiveeffects,H2Shasalsobeenshowntohavetherapeuticpotentialinotherareasofmedicine.Forexample,ithasbeenfoundtohaveanti-inflammatorypropertiesandmaybeusefulinthetreatmentofconditionssuchasarthritisandasthma.Ithasalsobeenshowntohavevasodilatoryeffects,potentiallymakingitusefulinthetreatmentofcardiovasculardisease.

Despiteitspotentialtherapeuticapplications,therearestillconcernsregardingthesafetyofH2Sasatreatment.H2Scanbetoxicinhighconcentrationsanditseffectsonthebodyarestillnotfullyunderstood.Furthermore,theuseofH2Sasatherapeuticagentmayraiseethicalconcerns,asithasthepotentialtoprolonglifebeyondwhatisnaturalormedicallynecessary.

Inconclusion,H2Sisacomplexmoleculewitharangeofphysiologicaleffectsonthebody,includingpotentialneuroprotectiveeffectsinthetreatmentofneurologicaldisorders.Whilemoreresearchisneededtofullyunderstandthemechanismsunderlyingitsactions,