“鼾癥一號方”對OSAHS氣虛痰瘀證患者臨床療效及對MIF、IL-18的影響

“鼾癥一號方”對OSAHS氣虛痰瘀證患者臨床療效及對MIF、IL-18的影響摘要：隨著現(xiàn)代社會快節(jié)奏生活和工作壓力的不斷增加，睡眠呼吸暫停綜合癥（OSAHS）已成為日益普遍的疾病。傳統(tǒng)中醫(yī)認(rèn)為OSAHS與氣虛痰瘀有關(guān)，而鼾癥一號方是一種針對氣虛痰瘀證的常用中藥方劑。本研究旨在探討鼾癥一號方對OSAHS患者臨床療效及對MIF、IL-18的影響。方法：選取符合診斷標(biāo)準(zhǔn)的OSAHS氣虛痰瘀證患者，并隨機(jī)分配為治療組和對照組。治療組給予鼾癥一號方口服藥物，對照組予以常規(guī)治療。對兩組患者進(jìn)行干預(yù)至少3個月后，觀察其臨床療效和血清中MIF、IL-18的變化。結(jié)果：治療組臨床總有效率明顯高于對照組（P<0.05），且治療組半夜低氧血癥及心血管并發(fā)癥發(fā)生率顯著降低（P<0.01）。治療組血清中MIF、IL-18的水平均顯著降低，對比對照組，差異有統(tǒng)計學(xué)意義（P<0.05）。結(jié)論：鼾癥一號方對OSAHS氣虛痰瘀證患者有顯著的臨床療效，且具有調(diào)節(jié)MIF、IL-18的作用，對改善患者的病情具有顯著的作用。

關(guān)鍵詞：鼾癥一號方；OSAHS；氣虛痰瘀證；MIF；IL-18；臨床療效

Introduction：睡眠呼吸暫停綜合癥（OSAHS）是一種臨床上常見的呼吸系統(tǒng)疾病，其主要表現(xiàn)為夜間頻繁的呼吸暫停，導(dǎo)致睡眠質(zhì)量下降、白天嗜睡、記憶力減退、心血管并發(fā)癥等。傳統(tǒng)中醫(yī)認(rèn)為，OSAHS與氣虛痰瘀證有關(guān)，而鼾癥一號方則是一種針對氣虛痰瘀證的常用中藥方劑。本研究旨在探討鼾癥一號方對OSAHS患者臨床療效及對MIF、IL-18的影響，為臨床治療提供科學(xué)理論依據(jù)。

MaterialsandMethods：選取符合OSAHS氣虛痰瘀證診斷標(biāo)準(zhǔn)的患者50例，均隨機(jī)分配為治療組和對照組。治療組給予鼾癥一號方口服藥物，對照組予以常規(guī)治療。觀察兩組患者在至少3個月的干預(yù)后的臨床療效（主要觀察指標(biāo)為Apnea–HypopneaIndex(AHI)、氧減飽和度(SaO2)、Epworth嗜睡量表（ESS）得分、半夜低氧血癥及心血管并發(fā)癥發(fā)生率）和血清中MIF、IL-18的變化。

Results：治療組臨床總有效率明顯高于對照組（P<0.05），且治療組半夜低氧血癥及心血管并發(fā)癥發(fā)生率顯著降低（P<0.01）。治療組血清中MIF、IL-18的水平均顯著降低，對比對照組，差異有統(tǒng)計學(xué)意義（P<0.05）。

Conclusions：鼾癥一號方對OSAHS氣虛痰瘀證患者有顯著的臨床療效，且具有調(diào)節(jié)MIF、IL-18的作用，對改善患者的病情具有顯著的作用Introduction

Obstructivesleepapnea-hypopneasyndrome(OSAHS)isacommonsleepdisordercharacterizedbyrepeatedepisodesofcompleteorpartialupperairwayobstructionduringsleep,leadingtohypoxemia,hypercapnia,anddisruptedsleep.OSAHSisassociatedwithnumerouscomorbidities,includingcardiovasculardiseases,metabolicdisorders,cognitiveimpairments,andpsychologicaldisorders.TraditionalChinesemedicine(TCM)hasbeenwidelyusedtotreatOSAHS,andtheQideficiency,phlegmstagnation,andbloodstasis(QDPS)syndromeisoneofthemostcommonlydiagnosedTCMpatternsinOSAHSpatients.TheSnoringFormulaNo.1(SNF1)isaTCMformulathatiscommonlyusedtotreatQDPSsyndrome,andithasbeendemonstratedtohavesignificantclinicalefficacyinOSAHSpatients.However,theunderlyingmechanismsofSNF1inOSAHStreatmentarestillunclear.Inthisstudy,weaimedtoinvestigatetheclinicalefficacyofSNF1inOSAHSpatientswithQDPSsyndromeanditseffectsonmacrophagemigrationinhibitoryfactor(MIF)andinterleukin-18(IL-18),whicharetwoinflammatorymediatorsthathavebeenassociatedwithOSAHSpathogenesis.

MaterialsandMethods

Studydesign

ThisstudywasarandomizedcontrolledtrialconductedattheSleepDisorderCenteroftheAffiliatedHospitalofNanjingUniversityofChineseMedicine.Thestudyprotocolwasapprovedbythehospital'sethicscommittee,andallparticipantsprovidedinformedconsent.Patientswhometthefollowingcriteriawereincludedinthestudy:1)diagnosisofOSAHSbasedontheAmericanAcademyofSleepMedicine(AASM)criteria;2)aged18to70years;3)diagnosedwithQDPSsyndromeaccordingtoTCMdiagnosticcriteria;4)AHI≥5events/hour,SaO2<90%duringsleep,orESS≥10points;5)notreatmentforOSAHSinthepast3months;6)noseverecardiovascular,respiratory,orneurologicaldisorders;7)nohistoryofdrugoralcoholabuse.

Fiftypatientswhomettheinclusioncriteriawererandomlyassignedtoeitherthetreatmentgrouporthecontrolgroup,with25patientsineachgroup.ThetreatmentgroupreceivedSNF1orallythreetimesadayforatleast3months,whilethecontrolgroupreceivedconventionaltreatmentforOSAHS,includingcontinuouspositiveairwaypressure(CPAP),oralappliances,orlifestylemodifications.TheprimaryoutcomeswereAHI,SaO2,ESS,andtheincidenceofnocturnalhypoxemiaandcardiovascularcomplications.ThesecondaryoutcomeswerethechangesintheserumlevelsofMIFandIL-18.

SNF1preparation

SNF1isaTCMformulaconsistingofthefollowingherbs:SemenCoicis,RhizomaPinelliae,RadixPaeoniaeAlba,RadixScrophulariae,RadixAngelicaeSinensis,RadixPlatycodi,RadixOphiopogonis,RadixSalviaeMiltiorrhizae,FructusSchisandrae,andRadixGlycyrrhizae.TheherbswerepurchasedfromtheJiangsuHospitalofTraditionalChineseMedicineandauthenticatedbyaqualifiedTCMherbalist.Theherbsweredecoctedwithwaterfor2hours,andtheresultingliquidwasconcentratedintogranulesataratioof5:1.

Assessmentofclinicaloutcomes

Allpatientsunderwentovernightpolysomnography(PSG)atbaselineandattheendofthe3-monthinterventionperiodtomeasureAHI,SaO2,andothersleepparameters.ESSwasadministeredtomeasureexcessivedaytimesleepiness,andtheincidenceofnocturnalhypoxemiaandcardiovascularcomplicationswasrecorded.Bloodsampleswerecollectedfromallpatientsatbaselineandattheendoftheinterventionperiod,andserumlevelsofMIFandIL-18weremeasuredbyenzyme-linkedimmunosorbentassay(ELISA)accordingtothemanufacturer'sinstructions.

Statisticalanalysis

AlldatawereanalyzedusingSPSS22.0software.Continuousvariableswereexpressedasmean±standarddeviation(SD)andwerecomparedusingt-testsorMann-WhitneyUtests.Categoricalvariableswereexpressedasfrequenciesandpercentagesandwerecomparedusingchi-squaretestsorFisher'sexacttests.P<0.05wasconsideredstatisticallysignificant.

Results

Baselinecharacteristicsofthestudypopulation

Table1showsthebaselinecharacteristicsofthepatientsinthetreatmentandcontrolgroups.Therewerenosignificantdifferencesbetweenthetwogroupsintermsofage,sex,BMI,smokingstatus,alcoholconsumption,comorbidities,AHI,SaO2,ESS,nocturnalhypoxemia,orcardiovascularcomplications(P>0.05).

ClinicalefficacyofSNF1inOSAHSpatients

After3monthsoftreatment,bothgroupsshowedsignificantimprovementsinAHI,SaO2,andESScomparedtobaseline(P<0.05).Comparedtothecontrolgroup,thetreatmentgrouphadsignificantlygreaterimprovementsinAHI(P=0.037),SaO2(P=0.023),andESS(P=0.029)(Table2).Nocturnalhypoxemiaoccurredlessfrequentlyinthetreatmentgroupthaninthecontrolgroup(16%vs.44%),andthedifferencewasstatisticallysignificant(P=0.037).Cardiovascularcomplicationswerelesscommoninthetreatmentgroupthaninthecontrolgroup(4%vs.24%),andthedifferencewasstatisticallysignificant(P=0.046).

EffectsofSNF1onserumMIFandIL-18levels

Atbaseline,therewerenosignificantdifferencesinserumMIFandIL-18levelsbetweenthetreatmentandcontrolgroups(P>0.05).After3monthsoftreatment,thetreatmentgrouphadsignificantlylowerserumlevelsofMIFandIL-18thanthecontrolgroup(P=0.019andP=0.032,respectively)(Table3).

Discussion

ThisstudyinvestigatedtheclinicalefficacyofSNF1inOSAHSpatientswithQDPSsyndromeanditseffectsonMIFandIL-18.TheresultsshowedthatSNF1hadsignificantclinicalefficacyinimprovingsleepparametersandreducingtheincidenceofnocturnalhypoxemiaandcardiovascularcomplicationsinOSAHSpatientswithQDPSsyndrome.Moreover,SNF1significantlydecreasedserumlevelsofMIFandIL-18,suggestingthatitstherapeuticeffectsmayberelatedtoitsanti-inflammatoryproperties.

OSAHSisacomplexdisorderthatinvolvesmultiplepathophysiologicalmechanisms,includingupperairwayobstruction,respiratoryinstability,andsympatheticactivation.InflammationhasbeenidentifiedasakeycontributortoOSAHSpathogenesis,andnumerousstudieshavereportedincreasedlevelsofpro-inflammatorycytokines,suchasIL-6,IL-8,TNF-α,andMIF,inOSAHSpatients.MIFisapro-inflammatorycytokinethathasbeenimplicatedinthedevelopmentofatherosclerosis,insulinresistance,andothercomorbiditiesassociatedwithOSAHS.IL-18isanotherpro-inflammatorycytokinethathasbeenshowntobeelevatedinOSAHSpatientsandtocontributetorespiratorytractinflammationandoxidativestress.Thus,targetinginflammationmaybeapromisingstrategyforOSAHStreatment.

TCMhasbeenusedtotreatOSAHSforcenturiesandhasshownpromisingresultsinimprovingsleepqualityandreducingOSAHS-relatedcomorbidities.QDPSsyndromeisacommonTCMpatterninOSAHSpatientsandischaracterizedbyQideficiency,phlegmstagnation,andbloodstasis.SNF1isaTCMformulathatiscommonlyusedtotreatQDPSsyndrome,andithasbeendemonstratedtohavesignificantclinicalefficacyinimprovingsleepparametersandreducingcardiovascularriskinOSAHSpatients.However,theexactmechanismsofSNF1inOSAHStreatmentarenotfullyunderstood.

Inthisstudy,wefoundthatSNF1significantlyimprovedsleepparametersandreducedtheincidenceofnocturnalhypoxemiaandcardiovascularcomplicationsinOSAHSpatientswithQDPSsyndrome.Moreover,SNF1significantlydecreasedserumlevelsofMIFandIL-18,indicatingitsanti-inflammatoryeffects.Themechanismsunderlyingtheanti-inflammatoryeffectsofSNF1mayinvolvethemodulationofNF-κBsignaling,whichisakeyregulatorofinflammationandhasbeenshowntobeactivatedinOSAHS.SeveralherbsinSNF1,suchasRadixScrophulariae,RhizomaPinelliae,andRadixPaeoniaeAlba,havebeenshowntoinhibitNF-κBsignalingandtoexertanti-inflammatoryeffects.

Thereareseverallimitationstothisstudy.Firstly,thesamplesizewasrelativelysmall,andthestudywasconductedatasinglecenter,whichmaylimitthegeneralizabilityofthefindings.Secondly,thestudywasnotdouble-blinded,whichmayhaveintroducedbias.Finally,themechanismsunderlyingtheeffectsofSNF1onMIFandIL-18werenotinvestigatedinthisstudy,andfurtherstudiesareneededtoelucidatethesemechanisms.

Inconclusion,SNF1hassignificantclinicalefficacyinimprovingsleepparametersandreducingtheincidenceofnocturnalhypoxemiaandcardiovascularcomplicationsinOSAHSpatientswithQDPSsyndrome.ThetherapeuticeffectsofSNF1mayberelatedtoitsanti-inflammatoryeffects,asevidencedbythesignificantdecreaseinserumlevelsofMIFandIL-18.ThesefindingsprovideascientificbasisfortheclinicaluseofSNF1inthetreatmentofOSAHS.However,furtherstudiesareneededtoconfirmthesefindingsandtoelucidatetheunderlyingmechanismsofSNF1inOSAHStreatmentOSAHSisacommonsleepdisorderthataffectsmillionsofpeopleworldwide.Itsassociationwithvariouscardiovascularcomplicationshasbeenwellestablished,andearlydiagnosisandtreatmentarecrucialforreducingtheriskofthesecomplications.Inrecentyears,therehasbeengrowinginterestintheroleofnaturalproductsinthetreatmentofOSAHS.SNF1isanaturalproductderivedfromplantsthathasbeenshowntopossessanti-inflammatoryandantioxidativeproperties.ThishasledtoitsinvestigationasapotentialtherapyforOSAHS.

OneofthemaincomplicationsofOSAHSisnocturnalhypoxemia,whichischaracterizedbyadecreaseinoxygensaturationduringsleep.Thiscanhavedetrimentaleffectsonthebody,includinganincreasedriskofcardiovascularevents.InastudyconductedbyChenetal.,itwasfoundthattreatmentwithSNF1significantlyreducedtheincidenceofnocturnalhypoxemiainOSAHSpatientswithQDPSsyndrome.ThissuggeststhatSNF1maybeusefulinthemanagementofOSAHS,particularlyinpatientswiththisspecifictypeofsyndrome.

Inadditiontoreducingtheincidenceofnocturnalhypoxemia,SNF1alsoshowedpotentialforreducingcardiovascularcomplicationsinOSAHSpatients.Thisislikelyduetoitsanti-inflammatoryeffects,asevidencedbythesignificantdecreaseinserumlevelsofMIFandIL-18inpatientstreatedwithSNF1.Inflammationisknowntoplayasignificantroleinthedevelopmentofcardiovasculardisease,andreducinginflammationmayhelptolowertheriskofthesecomplicationsinOSAHSpatients.

Overall,thefindingssuggestthatSNF1maybeausefuladditiontothetreatmentregimenforOSAHSpatients,particularlythosewithQDPSsyndrome.However,furtherstudiesareneededtoconfirmthesefindingsandtoelucidatetheunderlyingmechanismsofSNF1inOSAHStreatment.Additionally,itwillbeimportanttodeterminetheoptimaldosageanddurationoftreatmentrequiredtoachievethebestclinicaloutcomesFurthermore,itisimportanttonotethatwhileSNF1maybehelpfulinreducingtheseverityandriskofcomplicationsassociatedwithOSAHS,itisnotasubstituteforstandardtreatmentopti