[生物医药论文精品]玉米aceip及其降压作用的研究

1玉米ACEIP及其降压作用的研究摘要血管紧张素转化酶ANGIOTENSINICONVERTINGENZYME，ACE在人体血压调节过程中起重要的生理作用。玉米蛋白粉中的血管紧张素转化酶抑制肽ANGIOTENSINICONVERTINGENZYMEINHIBITORYPEPTIDES，ACEIP通过抑制ACE的活性产生明显的降血压作用。本文详细介绍了玉米ACEIP的作用机理、分离纯化工艺、检测和评价，简单介绍了其结构性质，比较分析了给药途径的影响，并对其应用前景进行了展望。关键词玉米活性肽血管紧张素转化酶降血压作用机理RESEARCHONTHEANTIHYPERTENSIONEFFECTOFCORNANGIOTENSINCONVERTINGENZYMEINHIBITORYPEPTIDESABSTRACTANGIOTENSINICONVERTINGENZYMEACEPLAYSANIMPORTANTPHYSIOLOGICROLEINTHEBLOODPRESSUREREGULATIONANGIOTENSINICONVERTINGENZYMEINHIBITORYPEPTIDESACEIPDERIVEDFROMCORNGLUTENMEALHAVESIGNIFICANTANTIHYPERTENSIVEEFFECTBYINHIBITINGACEACTIVATIONINTHEARTICLE,THESEPARATIONANDPURIFICATIONTECHNOLOGY,FUNCTIONALMECHANISM,THEDETECTIONANDEVALUATION,STRUCTURECHARACTEROFTHECORNANGIOTENSINCONVERTINGENZYMEINHIBITORYPEPTIDESAREREVIEWEDTHEEFFECTIONOFDIFFERENTADMINISTRATIONSISANALYZEDANDITSWIDEDEVELOPMENTALPROSPECTISFORECASTEDKEYWORDSCORNPEPTIDEACEANTIHYPERTENSIONFUNCTIONALMECHANISM据WHO估计,全球高血压患病人数已愈G24G1171,G6117G3281高血压患G13785高G17810G20G17G25G1171，G2469病G10587G1038G20G27G17G27G8，并G1000患病G10587G993G7041G990G2331。G2528G7114,高血压G2460G7171G1908G5527病、G14053G2342中、G5527G14051G2462G13970G2163G14033G15940G12481的G7380G1039要的G2469病G3252素,其G2373G4487G1177G8437G1122G13971G11256，G15999G3281G19481G990G12228G1038G256G7092G3780G7444G6175G257A1A0A2。G3252G8504高血压G19462G8847G6116G1038全球G2319G4410G11040G19766G1032的G980G20045G14404G5052的G1231G2165，降压药G10301G11752G12362已G6116G1038G3281G1881G3818G11752G12362的G9921G9869A3A4A5。G11458前G5132用降压药G1867G7389G14403G3921的降压G6940G7536，G1306G2528G7114G7389G980G4462的G2115作用G6122G993G14403G2465应A3A6A5,G1032G5214G990G7389望G7389G7044G3423降压药G1207G7379A3A7A5。G17829G5192G7481，G11752G12362人G2604G4570玉米蛋白转化G1038G980G1135G1867G7389G2163G14033性G6116分的蛋白G8712G16311G10301，G3926玉米蛋白肽G20290G7021、G1314G13870肽、G11107G8712肽G12573生G10301活性肽。玉米ACEIPG7171G980G12879G1867G7389抑制ACE活性的G3822肽G10301质,其G12373G1998G1260G9869G7171对高血压患G13785G2499G1209起G2052降压G6940G7536，对血压G8503G5132的人G7092降压作用,在G2319药和G1457G1593G20058G3507G7389G11540G5203G8879的应用价G1552。本文G1177对玉米ACEIP的结2构性质、分离纯化工艺、检测和评价G2462其降压作用机理G12573G11752G12362G10628G10378进行综述。1玉米ACEIP研究现状G20G17G20玉米蛋白粉G7481源、G6116分G2462营养价G1552G17829G5192G7481，随G11540产量的持续增长和玉米淀粉厂的增建与扩建，其G2115产G10301玉米蛋白粉（俗G12228黄粉）也随之大量增G3822。玉米蛋白粉G7171玉米经湿磨法工艺制得粗淀粉乳，再经蛋白质分离得G2052麸质G8712，然后浓缩干燥而制得,约含蛋白质G250G8G1209G990，还含G7389其它G7092机盐G2462G3822种维生素。G1306G11458前，G6117G3281玉米蛋白粉G1039要用作蛋白饲G7021G6122G13785当废G8712排掉，未得G2052合理的利用A3A8A5。G20G172玉米ACEIP的制备G2462分离纯化G11458前从食G10301蛋白质中制备ACEIP的途径G1039要G7389两种微生G10301G2469酵法和酶G16311法。G20G172G17G20微生G10301G2469酵法微生G10301G2469酵法的关键在G1122菌种的选择A3A9A5。前人G2469G10628瑞士乳杆菌G2469酵乳中ACEIP活性G7380高。NAKAMURAG12573人G11752G12362G1998工业生产ACEIP方法并已在美G3281申请了专利A3A10A5,其G1867体流程见图G20。原G7021溶G1122G8712原G7021溶G1122G8712灭菌灭菌冷却冷却至G2469酵温度原G7021溶G1122G8712接种培养灭菌G1039G2469酵剂冷却G2469酵培养第二G2469酵剂3通过分离柱G990清液离G5527G2469酵乳G2469酵甲醇洗脱过滤浓缩冷冻干燥HPLC分离ACEIP图G20ACEIP微生G10301G2469酵法制备流程G20G172G172酶G16311法ACEIP酶G16311法制备的G980般工艺流程G3926下A3A11A4A5原G7021提取蛋白质配G6116G200G8蛋白质溶液煮沸变性加酶G8712G16311灭活离G5527凝胶层析分离离子交换层析分离冷冻干燥检验ACEIP。G1209得G2052G7380大的ACE抑制活性G1038标准选择合G17878的蛋白酶,在G16825酶的G17878G4464G8712G16311G7477G1226下进行G8712G16311,G980般G1209得G2052G4625量G3822的G4579分子肽G1038G8712G16311结G7475的G6523制G7477G1226。G2568建G5191G12573G6265G17959A3A12A5的用G5515清G11909性蛋白酶生产大G16922ACEIP的酶G16311G7477G1226G1038温度G240G263,酶量G1038G23G8,G5225G10301浓度G1038G26G17G24G8,PHG1552G1038G28,G8712G16311G7114G19400G202H。G17225G18341G1860G12573G6265G17959A3A11A13A5的用G2992G9921菌蛋白酶酶G16311玉米G9207生产ACEIPG7477G1226G7171酶G5225比G20G297G240,PHG1552G1038G27,温度G25G24G263,G8712G16311G7114G19400G24H。G46UNIOG54UETSUNAG6265G17959A3A11A11A5的G13430G14406G15311G12879PORPHYRAYEZOENSISACEIP的酶G16311G7477G1226G1038温度G22G26G263,PHG1552G10382,G7114G1940020H,G13975蛋白酶酶G5225比G1038G22G297G2000。G2028G14817G12573G6265G17959A3A11A6A5的用G11909性蛋白酶0AG79CAG79ASE生产玉米ACEIP的酶G16311G7477G1226G1038PHG1038G27G170，温度G1038G24G24G16G250G263，G5225G10301浓度G10382G17G24G8，加酶量G1038G23G27AG56G18KG。G8712G16311度G20G24G17G28G25G8G7114G6164得G8712G16311G10301对ACE抑制作用G7380G5390。G20G172G17G22玉米ACEIP的分离纯化经蛋白酶G8712G16311后,得G2052大量的长G11713G993G12573,大G4579G993G980的G3822肽G9163合G10301,G1820用活性G9857G2572G19480G19512G2447较高分子量、未G8712G16311的蛋白质，用G17241滤G19512G2447G993溶G5225G10301、分子量较大的的蛋白质和肽G12879G1209G14731得合理的G11713肽，再G7693据分子大G4579，G4570G9163合G10301通过G3822G4392的凝胶G5214而G17810G2052分离的G11458的（凝胶过滤层析法）。G1306G11013G1122G16780G3822ACEIP的结构G19762G5132接G17829，分子量G5058G2047G10990微，在G17837种G5785G1929下，凝胶层析分离G6940G7536G993理G5831，G5460G5460G19668要结合离子交换层析A3A11A7A5。G1534G14685A3A11A14A5G12573用凝胶过滤G54EPHADEG91G42G162G24、离子交换层析和G2465G11468高G6940液G11468G14406G16901法对G8712G16311度G103820G8的酶G16311产G10301进行分离纯化，利用质G16901G18504G4462其中G980种ACEIP的G13464G6116G1038G42G79YG16G55YR。G20G17G22玉米ACEIP结构G17829G7481G11752G12362G15932明，玉米蛋白中含G7389高活性ACEIP，G3534本G5219G2027A3A11A9A5见G15932G20。其中G1209G989肽G4633G3822，并G1000大G18108分CG7423G12483G1038G14083G8700G18252。进G980G8505的G11752G12362G15932明CG7423G12483G1038PRO、G55YRG6122G5219G2027中含G7389G11107G8712G8700G3534G18252G7171维持抑制活性G6164G5529G20047的，而对G1122二肽NG7423G12483的G14471G20333G7075G8700G3534G18252与4ACE的结合G7171G7380G7389G6940的A3A4A4A15A4A6A5。G54G17G60ANOG12573A3A11A10A5在G8504G3534G11796G990G2460分离G1998G220G1325种玉米G11713G19154ACEIP。HG17G45G17G54UHG12573A3A11A8A5从玉米蛋白粉中分离G1998G5219G2027G1038PROG16G54ERG16G42G79YG16G42G79NG16G55YRG16G55YR的ACEIP，ICA14A13G1552G1038G2000G173MOG79G103LA16A11。G15932G20ACEIPG5219G2027G5219G2027ICA14A13G173MOG79G103LA16A11LEUG16ARGG16PRO0G172G26LEUG16G54ERG16PROG20G17G26G57AG79G16G54ERG16PROG200LEUG16G42G79NG16PROG20G17G28LEUG16ASNG16PROG23G22LEUG16LEUG16PROG24G26G57AG79G16AG79AG16G55YRG20G25LEUG16AG79AG16G55YRG22G17G28PHEG16G55YR2G24IG79EG16ARGG16AG79AG25G17G23LEUG16AG79AG16AG79AG20G22G57AG79G16AG79AG16AG79AG20G22LEUG16G42G79NG16G42G79NG2000IG79EG16ARGG16AG79AG16G42G79NG16G42G79NG20G250PYRG16G42G79YG16LEUG16PROG16PROG16G23G172ARGG16PROG16LYSG16IG79EG16PROG16PROPYRG16G42G79YG16LEUG16PROG16PROG16G42G79Y2G24G16PROG16PROG16IG79EG16PROG16PROG8892ICA14A13G6363G4570ACE活G2159抑制G240G8G7114，抑制剂的浓度2玉米ACEIP降压作用研究2G17G20玉米ACEIP的作用机理G8503G5132人体G1881血压G2475G5468G3822G3252素调节，其中G13970素血管紧张素调节G13007G13491（G53AG54）和G9620肽G18334G6930酶G9620肽G13007G13491（G46G46G54）G7171其中G980种重要的调节G13007G13491，ACEG7171G1209G990两G1022调节G13007G13491中起关键作用的酶,ACEIPG14033G3827G12466G1117性的与ACE结合，从而抑制其G2469G6393作用A3A11A12A5,G3926图2A17A18A19A20。5A21A22A23A24A25A26A27A22A28A29A30A31A32A33A34A23A30A31A28A29A35A36A37A38A39A40A41A42A40A43A39A41A42A44A45A46A35A36A37A38A39A47ACEIPA48A41A42A49A50A51A52A53A49A51A52A53A54A55A44A45A56A57A58A59A39A60A61ACEA62A63A64A44A35A36A37A38A39A65A48A44A42A66A67A68A35A36A69A38A49A35A36A70A71A72A53A49A50A51A52A53A73A74A75A73A76A77A78A79A80A81图2ACEIP对ACE的抑制作用2G172玉米ACEIP降压活性测G4462与评价对玉米ACEIP活性的测G4462通G5132G7389体G3818检测和体G1881检测两种。2G172G17G20体G3818检测玉米ACEIP的降血压作用通过对ACE活性的影响G7481体G10628。ACEIP测G4462的关键G7171ACE活性的测G4462，G5132用G6363标G1038ICA82A83。，ACE的酶G1664化作用G7171G1209ANGG1038G5225G10301，G4570ANG转化G1038ANGG266，通过分G1821G1821度法测G4462G17837G980G2465应过程的G5225G10301浓度变化，G13484制标准G7366G13459，G2499G1209G5567G17907测G4462G1998ACEIP活G2159A84A85A86A87。体G3818检测G980般G18129G7171采用CUSHMAN和CHEUNG的检测方法。G20G28G26G20G5192CUSHMANG12573建立了紫G3818G1821度法A84A88A83A87。ACE在G22G26G263、PHG27G17G22的G7477G1226下G1664化分G16311血管紧张素I的模拟G10301HIPPURYG16LG16HISTIDYG79G16LG16LEUCINEHHL产生马尿G18252,G16825G10301质在紫G381822G27NM处G1867G7389特征G2572收峰。当加入ACEIPG7114,ACE对HHL的G1664化分G16311作用G2475G2052抑制,马尿G18252的生G6116量减少。通过测G4462加入ACEIP前后G6164生G6116马尿G18252紫G3818G2572收的大G4579G5058G2047即G2499算G1998抑制活性的大G4579。G1306G16825方法对实验操作要求G10990高,实验易产生误G5058。后G7481G16780G3822G4410G13785对其进行了改进,其中NIG79I的高G6940液G11468G14406G16901法直接G4570G2465应液用G1122马尿G18252的G4462性G4462量分析,G993G19668经过乙G18252乙酯抽提马尿G18252的繁琐过程,操作简便,准确性高A84A85A88A87。2G172G172体G1881检测体G1881检测分G1038两G12879A84A88A85A87,G980G12879动G10301试验,另G980G12879G7171人体G1032G5214试验。动G10301试验G980般6G1209患原G2469性高血压的大鼠SPONTANEOUSG79YHYPERTENSIVERATS,G54HG53G1038G11752G12362对象,ACEIP的活性大G4579G2499通过测量G54HG53摄入前后的动脉收缩压G7481G2465映其作用大G4579,血压降G1314越明显、持续G7114G19400越长,则说明ACEIP的活性越高、降压G6940G7536越G3921。而摄入方法大G3822采用G13975插管法,也G7389G11752G12362G13785采用直接口服G8892射方式。按摄入G8437数G7481分G2460G2499分G1038两种G980种G1038G980G8437性检测,只G7171测口服前后的血压变化另G980种G1038长期实验,每天G980G8437G6122每周G980G8437连续几周,G10990至十几周摄入ACEIP观察收缩压的变化A84A85A88A87。ACEIP的活性与实验降血压G2163G14033的关G13007仍G7389待进G980G8505深入G11752G12362。3玉米降压肽的应用前景G3281G3818对G1122食品蛋白G7481源的ACEIP的G11752G12362已G17241过20G5192,已G7389产品G990市。玉米ACEIP只对高血压患G13785起降压作用,对血压G8503G5132G13785G7092降压作用，安全性G5468高，G1867G7389较G3921的G18252G9921稳G4462性和G8712溶性G12573理化特性，G3252G8504，用G1122预G19462、缓G16311和G8847疗高血压,G5529G4570G1038人们G6164接G2475。G1306G7171玉米ACEIP口服易G2475G13975肠G17959酶的作用而失活，G8892射给药、皮肤给药、肺G18108给药G12573G7044的给药途径G1209G2462脂质体、微乳、传递体G12573载体技术的G2469展G1038其G5203G8879应用提供G7044的思路。随G11540G10628G1207蛋白质工程、生G10301酶工程技术迅G17907G2469展、生G10301技术的应用G2462G3281G1881G5203G8879的原G7021,G2499生产G1998大批量玉米ACEIP应用G1122食品、G1457G1593，G2319药G12573。G19766对G993G7041增加的高血压患G13785的G19668求,G17837方G19766的产品G1867G7389显著的社会G6940益和经济G6940益,孕育G11540G5052大的商机,G1867G7389G5203阔的G2469展前景。参考文献A89A90A91A92A93A94A95A96A97A98A99A100A101A102A103A104A105A106A107A108A109A110A89A111A91A95A112A113A114A115A116A117A118A119A120A120A120A118A90A121A122A119A123A124A90A125A119A126A90A125A125A90A95A89A119A91A127A128A129A130A131A132A133A134A135A136A137A127A128A129A130A131A132A133A138A116A139A140A136A137A127A128A129A130A131A132A133A133A141A142A143A144A145A146A127A133A147A130A148A149A150A151A152A107A153A119A120A120A119A89A154A91A95A155A156A124A129A130A134A135A157A158A159A137A119A120A120A160A95A90A160A161A90A162A95A89A163A91A164A165A166A95A96A97A98A101A100A167A168A169A89A111A91A95A170A171A172A173A174A175A137A119A120A120A90A137A121A176A162A177A178A162A125A126A162A160A95A89A125A91A179A180A181A118A182A95A96A97A98A183A184A185A186A187A188A98A173A100A167A189A190A89A111A91A95A127A133A191A187A192A138A193A194A118A90A121A121A125A137A90A125A176A119A177A124A90A90A160A126A90A90A162A95A89A160A91A195A196A197A95A96A97A98A100A167A102A168A169A89A111A91A95A127A128A192A138A193A194A118A90A121A121A198A137A163A162A176A121A177A124A162A163A199A95A89A162A91A200A201A202A137A203A151A137A204A205A206A95A207A208A209A210A211A212A213A214A215A216A217A218A219A220A221A222A223A224A225A226A227A228A229A230A231A232A233A233A234A231A232A235A236A237A238A239A240A234A241A242A233A233A224A221A234A223A243A244A245A246A247A248A249A246A247A250A251A246A252A224A253A254A255A150A0A153A1A2A3A4A5A6A217A7A3A8A9A221A222A223A224A50A10A4A228A214A163A246A232A233A233A235A236A232A238A48A240A241A242A242A224A221A16A223A247A248A249A246A243A244A245A224A4A157A255A150A0A153A1A11A46A110A12A13A14A47A217A8A9A225A25A221A222A223A224A227A228A139A15A17A214A163A246A232A233A233A242A236A242A242A238A48A234A233A241A234A235A224A221A240A223A122A18A19A246A170A20A21A224A173A22A110A13A14A217A8A1A46A23A23A47A241A24A0A176A216A26A27A217A28A29A221A222A223A224A50A10A30A31A246A242A240A240A16A236A235A238A48A32A241A16A224A221A242A233A223A183A33A34A224A216A207A208A109A35A36A110A12A13A2A3A14A221A222A223A224A227A228A139A37A38A246A242A240A240A16A236A82A238A48A234A241A16A224A221A242A242A223A189A39A40A41A42A43A39A44A45A49A39A40A51A224A222A52A51A53A41A40A44A54A41A42A45A44A55A56A40A42A57A246A242A240A240A16A236A32A238A48A242A32A235A241A242A32A234A224A221A242A232A223A205A58A59A231A33A184A60A224A227A228A209A210A61A50A12A62A63A243A64A65A29A24A153A1A14A217A8A9A221A222A223A224A35A66A230A67A68A69A231A232A233A233A237A236A32A238A239A32A241A242A233A224A221A242A235A223A214A251A231A125A70A71A231A217A72A73A224A24A74A207A208A209A210A1A75A110A12A13A14A217A8A9A221A222A223A224A227A228A214A163A229A230A231A232A233A233A32A231A232A234A236A82A238A239A242A242A234A241A242A232A232A224A221A242A237A223A222A76A231A224A207A77A231A252A224A227A228A209A210A110A12A13A14A78A79A8A9A219A220A221A222A223A224A227A228A8A9A139A80A15A231A232A233A233A237A231A232A82A236A82A238A2397A235A241A234A224A221A242A82A223A228A81A231A252A224A12A62A63A243A64A24A2A3A153A1A11A230A230A231A64A14A217A83A84A85A234A29A86A87A88A89A90A221A222A223A224A239A91A231A232A233A233A242A236A235A238A239A232A232A232A241A232A232A82A224A221A242A32A223A222A41A40A52A51A40A189A41A92A231A222A42A40A93A94A95A39A40A96A56A51A40A93A231A94A95A39A40A93A222A42A42A43A39A56A224A0A40A56A51A40A55A44A92A44A40A45A42A152A51A40A93A41A42A45A44A40A49A41A40A23A55A42A40A202A44A53A45A41A40A93A44A40A97A95A92A44A41A40A56A41A98A41A45A42A53A95A51A55A45A41A202A41A45A95A51A40A198A41A92A99A53A42A202A44A92A44A40A45A42A152A45A56A44A44A92A39A57A49A41A152A95A41A40A93A51A40A198A152A42A51A92A41A40A93A99A53A42A99A44A53A45A41A44A49A42A152A55A42A53A40A93A57A39A45A44A40A56A95A198A53A42A57A95A49A51A45A44A39A49A41A40A93A39A57A45A53A51A152A41A57A45A53A51A45A41A42A40A92A44A92A98A53A51A40A44A49A221A222A223A224A0A39A53A100A42A42A198A101A44A49A102A44A55A56A40A42A57A231A232A233A233A237A231A232A242A16A48A242A235A235A254A242A235A16A224A221A242A234A223A52A41A95A42A49A56A41A43A246A23A49A56A41A103A51A104A51A94A246A189A51A40A44A103A42A102A246A44A45A51A57A224A43A45A53A39A55A45A39A53A44A49A51A40A198A51A55A45A41A202A4