罗布麻叶提取物对两肾一夹加高糖高脂饮食大鼠肾性和肥胖型高血压的保护作用

Preventionofrenalandobesity-relatedhypertensionin2K1Cratsonhigh-fatandrefined-carbohydratedietbyApocynumvenetumL.leafextractXiang-qiWu12,Xin-boYang*1,Jie-renYang2,Zheng-mingHuang3,Hong-yanChen1,MiaoGeng1,Jian-huaWang1(1InstituteofGeriatrics,GeneralHospitalofPLA,Beijing100853China)(2DeptofPharmacology,WannanMedicalCollege,WuhuAnhui241001China)(3DeptofPharmacy,Hospital302ofPLA,Beijing100853China)Abstract:AIM:ToobserveantihypertensiveeffectsofApocynumvenetumL.leafextract(ALE)andexploreitspartmechanismin2-kidney,1-clip(2K1C)ratsonhigh-fatandrefined-carbohydratediet.METHOD:Ratswithmetobolicsyndromewerecopiedbytwo-Kidney,one-Clipmethodandhigh-fatandrefined-carbohydratedietfortwelveweeks.Systolicbloodpressure(SBP)wasdeterminedat5thweek,forty-tworatswithSBPexceeding160mmHgwererandomlyassignedtofivegroups:ALEwithhigh-,middle-andlow-dosegroups(200,100,50mg·kg-1·d-1,n=8),captoprilgroup(30mg·kg-1·d-1,n=8)andmodelgroup(0.5%carboxymethylcellulose5ml·kg-1·d-1,n=10),anotherlayingsham-operatedgroup(0.5%carboxymethylcellulose5ml·kg-1·d-1,n=10).Ratswereintragastricadministratedbetween9:00-10:00everydayforeightweeksaccordingtoabove-mentionedsettingdosage.Bodyweightwasrecordedweekly,andthedosewasadjustedadcordingtoweightchanges.At5th,9thand13thweek,SBPandurinaryvolumefor24hoursweredetermined.At13thweek,bodyweight,leftclippedkidneyweightandwhiteadiposetissuehumidweight(WHW)wereweighed,oxidativeandantioxidativeindexesforclippedkidneytissue,levelsofangiotensinⅡandaldosteroneforplasma,contentofinsulin,leptin,TNF-α,IL-6,TG,TC,ScrandBUNforserumweremeasured.Pathologicalchangesoflivertissuewasobservedbyhematoxylin-eosinstainingmethod.RESULTS:ALEtreatmentsignificantlyreducedestablishedhypertensionat9thand13thweek.Thelevelofoxidativeindexinclippedkidney,theplasmaangiotensinIIandaldosteronelevels,theseruminsulin,leptin,TNF-α,IL-6,TG,TC,ScrandBUNcontentinserumweremarkedlyreduced,urinaryvolumefor24hourstendedtoincreaseat9thand13thweek,andHEstainingrevealedthatlipidosesinlivercellsandinflammatorycellinfiltrationinhepaticlobulesandportalareawereamelioratedafterALEtreatment.Inaddition,ALEtreatmentcanimproverenalfunctionandantioxidativecapabilityinclippedkidney.CONCLUSION:ALEcanattenuate2K1Candobesity-relatedhypertensionin2-kidney,1-clip(2K1C)ratsonhigh-fatandrefined-carbohydratediet,oneofthemechanismscouldbeclosewithreducingtheamountsoftheplasmaangiotensinIIandaldosteronebyimprovingrenalfunctionthroughitsantioxidativeeffectinclippedkidneytissue,andanotheronecouldbethatitimprovedinsulinresistancebydecreaseinlipidosesinlivercellsandenhancementofleptinsensitivitywhichleadedtothereductiononlevelsofTNF-αandIL-6forserum.Keywords:apocynumvenetumL;leafextract;renalhypertension;obesity-relatedhypertension;metabolicsyndrome;rat*Correspondentto:YangXinbo,[e-mail]1IntroductionThemetabolicsyndromeinadultshasbeendefinedasaclusterofthemostdangerousriskfactorsforcardiovasculardiseaseandtype2diabetes,whichincludeabdominalobesity,highcholesterol,highbloodpressure,diabetes(ifnotyetpresent)andraisedfastingplasmaglucose[1].Globallifestylechanges,includinganincreaseinthecaloricintakeandareductioninphysicalactivity,havesharplyincreasedthenumberofpatientswithmetabolicsyndrome.Already,aquarteroftheworld’sadultpopulationhasmetabolicsyndromeandthisconditionisappearingwithincreasingfrequencyinchildrenandadolescents,duetothegrowingobesityepidemicwithinthisyoungpopulation[2-4].Peoplewithmetabolicsyndromearetwotothreetimesaslikelytohaveaheartattackorstrokecomparedwithpeoplewithoutthesyndrome[1].ApocynumvenetumL.(Apocynaceaefamily),knownas‘‘Luobuma’’inourcountry,isawildplantthatgrowswidelyinthemiddletonorthwesternregions,whereitsleavesarecommonlyusedtomaketea.Theyhavealsobeenusedtotreatcardiacdisease,hypertension,nephritis,neurasthenia,andotherdiseases[5].Inrecentstudies,anextractfromtheleavesofA.venetumhasbeenreportedtoshowaantioxidantactivity,lipid-loweringeffect,hepatoprotectiveeffect,antidepressantactivityandanti-anxietyeffect[6-10].Inpreviousstudy,wealsofoundthatALEhasprotectiveeffectsonfocalcerebralischemiareperfusioninjuryinratsanditcouldbecloselyassociatedwithitsantioxidantactivity[11].AccumulateddatasuggestedthatextractsofApocynumvenetumL.leaveshadantihypertesiveeffectonspontaneouslyhypertensive,renalhypertensiveandNaCl-fed-hypertensiverats[12-14],butitsantihypertesiveeffecton2K1Chypertensiveratsonhigh-fatandrefined-carbohydratediethavenotbeenreported,sowewantedtoexaminetheeffectofALEonsecondaryhypertensioninducedbyclippingofonerenalarteryandonhigh-fatandrefined-carbohydratediettoseewhetherALEcouldinterferedevelopmentofrenalandobesity-relatedhypertensionandexploreitspartmechanisminthepresentstudy.2Materialsandmethods2.1ExperimentalanimalsFifty-twomaleSprague-Dawleyrats(CertificateNoSCXK(jing)2007-0001)weighing200～240gwerepurchasedfromBeikingWeitongLihuaexperimentalanimaltechniquelimitedcompanyandhigh-fatandarefined-carbohydratefeed(25%canesugar，15%axungiaporci，5%eggyellow，2%cholesterin，53%commonfeed,CertificateNoSCXK(jun)2002-018)wereprovidedbytheanimals