[生物医药论文精品a]桑叶总黄酮对高脂血症动物的降血脂效应

桑叶总黄酮对高脂血症动物的降血脂效应李向荣A1陈菁菁A2（1，浙江大学城市学院医学院，杭州，310015；2，浙江大学药学院，杭州，310058）摘要目的观察桑叶总黄酮的降血脂作用。方法用TRITONWR1339诱导建立急性高脂血症小鼠模型和高脂饲料建立高脂血症大鼠模型，分别测定小鼠和大鼠血清中的总胆固醇（TC）、甘油三脂（TG）、高密度脂蛋白胆固醇（HDLC）和低密度脂蛋白胆固醇（LDLC）的含量，并计算HDLC/TC和HDLC/LDLC的比值。结果桑叶总黄酮（MTF）能显著抵抗TRITONWR1339诱导的小鼠血清TG，TC和LDLC等指标的升高，同时升高血清HDLC/TC和HDLC/LDLC的比值。给药后12H作用效果更明显。喂高脂饲料的大鼠模型也同样表明MTF具有降低血脂的作用，而且具有剂量G4007G2304性。结论MTF能剂量G4007G2304性G1305降低高脂血症小鼠和大鼠的血脂G3331G2876，G4167G1469高脂血症的G1439G3219G1439G4282。G1681G1999G1197桑叶总黄酮TRITONWR1339高脂血症小鼠大鼠高脂血症G4068G2927G1358G2557G4415样G4087G1828G3262G4239G1102G1683G3823G968、高血G3906和血G1685G1925G968的G4438G3985G4176G4057。G3649G1715G3078G3061血脂G4051G1064G3833G3261G3928G2189，G3928G4407G3599G3805G3649G1715G3078G2646的G2002G2210。G3649G171518G3391G1923G4027G3176G1102G3078血脂G4051G1064总G1841G968G2513G123418G17G25G8，G1927血脂G4051G1064G1841G4320G4024G12341G17G25G4033；而且血脂G4051G1064的G1439G968G2513G4350G3028向G2733G3006G1828，中G2733G3078G4144G2330G2733G3078G1841G968G2513G3757G2093A4A1A0。G4057G1198，G4531G1754血脂G4051G1064的G4234G2905G1469G4397，G3929G2126G1336G2059血脂效果G1754、G1373G1548作用小的G3821药G3237分G4407G3985。G3747G1245G3929G2126表明，G1558含黄酮G2347G1828G1766G3678的G4369G3678G3476G3036G3678具有降低血脂、清G1154G3480G2717G4497G4110G1902、G4029G4389脂G4393G1718G3966G1828的G1891性A4A2A0，G3649G2604G3929G2126G1439G3747桑叶含有G1502G1558的黄酮G2347G1828G1766G3678。G903G3244G3954G4379G4221观察桑叶总黄酮G1395TRITONWR1339诱导的高脂血症小鼠模型和高脂饲料G4068G2927高脂血症大鼠模型的血脂的G4085G3769，G3609G2089G4002G996G3929G2126桑叶总黄酮的药G2360作用G3476G1634G1902G1156。1材料与方法1G171药G2870G4144G3275剂TRITONWR1339（G54IG74MA，美G1715）；银杏黄酮片（深圳海王药业有限公司，广州，批号20041108）；TG、TC测G3275盒（南京建G1102G3219G3678工程G3929G2126所，南京）；HDLC、LDLC测定G3275剂盒（荣盛G3219G3678，G3176海）；其他G3275剂均G3609分析纯。1G172G3244G3954G1358G3678ICR小鼠，202G74；G54D大鼠，2002G74，雌雄各半，均购于浙江省医学科学院G3244G3954G1358G3678中G3823。G3244G3954G1358G3678饲养G4002周G4027适应G903G3244G3954室条件，分笼饲养，G1358G3678可G4027G4497G4110饮G3331，摄G3036普通饲料，控G4389G3244G3954室光照12H明12H暗，室G2717温度G3609241，湿度G36095510G8。13方法A3A53G171药G3678G3275液的G4389备G3036桑叶总黄酮样G2870（G3649G2604G3244G3954室G4389备），分别配G1102浓度G36090G175，1和2MG74MLA6A1。银杏黄酮溶液浓度G36091MG74MLA6A1，于4保存备用。132G1358G3678G3244G39541321急性高脂血症小鼠模型将ICR小鼠随机分G3609G25组G4350G1064G1395照组，模型G1395照组，MTFG3244G3954组（7G175、15和30MG74KG74A6A13个剂量组）和阳性G1395照组。G1154G4350G1064G1395照组外，其他各组分别尾静G2557注射TRITONWR1339（400MG74KG74A6A1）诱导血脂升高，G4350G1064G1395照组注射等G3480积NG54。注射TRITONWR1339后12H，G3244G3954组分别用MTF药液灌胃（剂量分别G36097G175、15和30MG74KG74A6A1），阳性G1395照组G4027银杏黄酮灌胃（15MG74KG74A6A1）。TRITONWR1339注射后的12H、18H和24H，每组随机选G303610只，去眼球采血，分离血清，38保存，G1634血脂指标测定用。1322高脂血症大鼠模型A4A7A0将48只G54D大鼠随机分G3609G25组G4350G1064G1395照组，喂普通饲料；模型G1395照组，喂高脂饲料（高脂饲料组G1102G4393量分数G3609猪油10G8，蛋黄粉10G8，胆固醇1G8G1923G1902G1156饲料79G8）；3个剂量的MTFG3244G3954组和阳性G1395照组也喂食高脂饲料，并分别灌胃给予MTF（分别G36095、10和20MG74KG74A6A1）和银杏黄酮（10MG74KG74A6A1），每天G4002次，连续4周。同时，G4350G1064G1395照组和模型G1395照组分别灌胃给予等G3480积NG54。于每周测定G3480G4407。G3244G3954前后，分别尾静G2557采血，分离血清，38保存，G1634血脂指标测定用。G3244G3954结束后，断头处死，G3036肝脏并称G4407，并计算肝G4407指数（HEPATOSOMATICINDICES,HG54I）。肝G4407指数（HG54I）（肝脏G4407量/G3480G4407）1001323血脂指标测定按G3275剂盒说明书方法G1024作，分别测定小鼠和大鼠血清中的总胆固醇（TC）、甘油三脂（TG）、高密度脂蛋白胆固醇（HDLC）和低密度脂蛋白胆固醇（LDLC）的含量，并计算HDLC/TC和HDLC/LDLC的比值。1324G3524计方法数G2156G4027G2876均值标G4473G1045表G3253，采用G3524计G3112件（G54G51G54G5413G170G73ORWINDOG90S）G2089G3835方G1045分析，G2406组G1975比G2048采用TG1983G3954。2结果21MTFG1395TRITONWR1339诱导的高脂血症小鼠血脂指标的G4085G3769G4144G4350G1064G1395照组G3757比，注射TRITONWR1339的小鼠的血清TG、TC和LDLCG3331G2876分别升高G2420G41917G895、5G895和4G895，HDLC/TC和HDLC/LDLC比值分别降低G242040G268和10G268，建立G2420急性高脂血症小鼠模型。而给予MTF处G2360（剂量分别G36097G175、15G189530MG74KG74A6A1）的小鼠明显G4029G4389TRITONWR1339诱导的高脂血症小鼠血脂G3331G2876的升高（G1998表21G9表22）。TAG69LE21G40G73G73ECTOG73MTFONSERG88MLIPIDLEG89ELSINMICE18HPOSTTRITONWR1339ING77ECTIONG11NG3210G30MEANG54G17DG17G12A8A9A10A11A12A11A3A13A14A15A16A17A18A19A16A20A21A19A16A22A23A12A24A9A10A11A12A11A25A26A24A24A9A10A11A12A11A3A13A14A27A16A28A29A20A21A19A16A22A23A12A30A31A32A33A34A35A36A32A37A38A31A39A40A41A42A43A44A44A45A46A36A47A38A32A48A34A38A33A48A39A38A49A33A50A51A52A50A53A54A55A56A37A39A52A50A48A38A37A39A49A43A57A33A50A51A52A50A53A54A55A58A59A57A43A57A44A60A36A56A49A33A50A51A43A60A60A33A35A53A54A55A61A57A59A58A62A57A59A45A63A60A58A59A57A62A64A45A59A45A65A57A45A57A59A45A62A57A45A59A44A57A57A44A59A43A62A57A64A59A57A66A64A44A58A59A45A62A44A61A59A60A66A66A57A64A67A59A67A62A64A58A59A43A66A66A36A68A49A33A50A51A43A60A60A33A35A53A54A55A58A45A59A43A62A57A59A64A64A64A60A59A63A62A67A45A59A63A65A64A43A67A59A61A62A64A60A59A45A44A63A43A59A67A62A44A64A59A63A66A66A67A61A57A59A57A62A67A58A59A60A66A66A44A58A60A59A67A62A44A67A59A44A66A66A69A70A69A42A68A49A33A50A51A43A60A60A33A35A53A54A55A58A67A59A43A62A57A59A43A67A61A58A59A67A62A67A44A59A58A65A67A58A44A59A44A62A67A57A59A43A67A64A57A59A58A62A67A63A59A43A66A66A67A43A60A59A64A62A43A63A59A44A66A66A67A64A61A59A60A62A67A60A59A57A66A66A71A70A69A42A68A72A36A68A60A59A57A67A62A60A59A60A64A60A59A44A64A62A60A59A60A44A65A60A59A44A64A62A60A59A60A44A60A59A44A63A62A60A59A60A44A60A59A44A45A62A60A59A60A64A66A66A60A59A44A63A62A60A59A60A44A71A70A69A42A68A72A69A70A69A42A68A60A59A57A58A62A60A59A60A57A60A59A57A67A62A60A59A60A63A65A60A59A57A67A62A60A59A60A64A60A59A57A44A62A60A59A60A57A60A59A57A44A62A60A59A60A63A60A59A57A64A73A60A59A60A63TAG69LE22G40G73G73ECTOG73MTFONSERG88MLIPIDLEG89ELSINMICE24HPOSTTRITONWR1339ING77ECTIONG11NG3210G30MEANG54G17DG17G12A74PG310G1701VSCONTROLG74ROG88PG17G13PG310G1705,G13G13PG310G1701VSMODELG74ROG88PG17G3106表22所G3253，尾静G2557注射TRITONWR1339（400MG74KG74A6A1）24H后，模型组的小鼠血清中的TG、TC和LDLC含量分别G3609540G171、4G253G177和298G178MG74100MLA6A1，而G402715和30MG74KG74A6A1剂量MTF给药的小鼠血清中的TG、TC和LDLC含量分别降低G1278494G170、339G175、228G179MG74100MLA6A1和388G170、25G25G17G25、189G172MG74100MLA6A1；HDLC/TC比值G4221模型组小鼠中降G1278G24200G1733，而G4221MTF给药（15和30MG74KG74A6A1）的小鼠中G1869升G1278G24200G1738和0G1742；MTF给药的小鼠血清中HDLC/LDLC比值G4144模型组G3757比也有所升高，G1260G2592有显著性G1045G4051。表21和表22均表明MTF能G4029G4389TRITONWR1339诱导的小鼠血脂G3331G2876的升高，且具有剂量G4007G2304性。G353321更清G1155G1305显G3253G2420MTF能剂量G4007G2304性G1305G4029G4389G4110TRITONWR1339静G2557注射G4068G2927的小鼠血清TG、TC和LDLCG3331G2876的升高G4027G1923HDLC/TC和HDLC/LDLC比值的G3727降。A30A31A32A33A34A35A36A32A37A38A31A39A40A41A42A43A44A44A45A46A36A47A38A32A48A34A38A33A48A39A38A49A33A50A51A52A50A53A54A55A56A37A39A52A50A48A38A37A39A49A43A57A33A50A51A52A50A53A54A55A58A59A57A43A57A44A60A36A56A49A33A50A51A43A60A60A33A35A53A54A55A61A64A59A57A62A57A59A64A57A64A60A59A43A62A44A45A59A45A65A57A67A63A59A57A62A64A63A59A44A64A45A64A59A60A62A64A57A59A61A66A44A61A61A59A60A62A67A63A59A44A66A66A64A57A43A59A61A62A44A58A59A58A66A66A36A68A49A33A50A51A43A60A60A33A35A53A54A55A61A43A59A43A62A64A59A45A64A63A44A59A58A62A44A63A59A61A65A64A67A60A59A63A62A64A64A59A60A66A44A44A45A59A57A62A44A67A59A58A66A66A67A57A63A59A63A62A67A64A59A61A66A66A44A64A64A59A61A62A64A60A59A44A66A66A69A70A69A42A68A49A33A50A51A43A60A60A33A35A53A54A55A58A67A59A58A62A57A59A57A67A45A61A59A61A62A67A57A59A45A65A67A58A57A59A45A62A67A67A59A67A66A67A67A61A59A45A62A43A58A59A64A66A66A43A61A45A59A67A62A43A63A59A44A66A66A67A44A58A59A63A62A43A61A59A45A66A66A71A70A69A42A68A72A36A68A60A59A57A67A62A60A59A60A44A60A59A44A44A62A60A59A60A44A65A60A59A44A64A62A60A59A60A44A60A59A44A61A62A60A59A60A64A66A66A60A59A64A67A62A60A59A60A64A66A66A60A59A44A58A62A60A59A60A64A66A71A70A69A42A68A72A69A70A69A42A68A60A59A57A61A62A60A59A60A57A60A59A57A67A62A60A59A60A64A65A60A59A57A67A62A60A59A60A58A60A59A57A63A62A60A59A60A64A60A59A57A58A62A60A59A60A63A66A60A59A57A44A62A60A59A60A630010020030040050060070080090010000102030DOSAGEOFMTFMG/KGINHIBITIONRATIOTGTCLDLCHDLC/TCHDLC/LDLCA75A76A77A78A79A80A81A82A83A84A76A85A83A86A87A76A88A86A88A76A89A85A89A90A91A82A75A76A85A92A84A93A94A95A96A76A97A76A98A96A84A99A84A96A92A78A82A83A84A92A84A93A94A95A96A76A97A76A98A96A84A99A84A96A92A100A84A93A84A93A84A92A76A92A88A84A98A87A101A91A82A75A102A86A88A88A83A84A98A89A92A84A92A89A90A103A78A104A102A81A104A86A85A98A105A106A95A77A107A77A108A109A102A79A110A83A97A89A92A88A88A93A76A88A89A85A111A112A80A81A105A105A113A76A85A114A84A115A88A76A89A85A78A116A86A88A84A76A92A84A117A97A93A84A92A92A84A98A86A92A95A84A86A85A118A119A78A116A78A89A87A88A86A76A85A84A98A90A93A89A95A88A84A85A95A76A115A84A76A85A84A86A115A83A77A93A89A94A97A7822MTFG1395高脂血症大鼠的G4085G3769G1206表23可G4027观察G1278，喂高脂饲料的同时给予MTF保G1817的大鼠各血脂指标明显G1754G4455。剂量G360910和20MG74KG74A120A121DA120A121的MTFG3244G3954组大鼠的TG、TC和LDLCG3331G2876分别G3611G1115G422173G172、8G25G174、51G177MG74100MLA120A121和G257G172、84G170、47G175MG74100MLA120A121，G3757比模型组明显G3727降。G3385G3062MTFG3244G3954组（10和20MG74KG74A120A121DA120A121）大鼠的HDLCG3331G2876分别升高G127848G17G25和50G175MG74100MLA120A121，G3757比模型组HDLCG3331G2876G2087G360943G178MG74100MLA120A121，G1260G1198G1045G4051G994具显著性。TAG69LE23G40G73G73ECTOG73MTFONSERG88MLIPIDLEG89ELSINHG92PERLIPIDEMICRATSG11NG328G30MEANG54G17DG17G12A122A123A124A125A126A127A128A123A129A130A127A128A131A132A133A124A130A126A133A125A130A134A133A135A125A136A137A138A136A139A140A141A142A143A134A138A136A130A133A143A134A135A144A145A125A136A137A138A136A139A140A141A146A144A145A147A145A131A142A135A125A136A137A144A145A145A125A127A139A140A141A148A146A149A150A151A144A145A149A148A152A153A149A146A151A144A147A149A153A154A155A147A149A147A151A144A146A149A150A150A153A149A147A151A152A149A152A156A148A150A149A147A151A144A155A149A145A156A156A150A144A149A155A151A144A148A149A147A156A131A157A135A125A136A137A144A145A145A125A127A139A140A141A150A153A149A147A151A144A147A149A155A144A145A155A149A147A151A144A155A149A148A154A144A145A147A149A153A151A147A158A149A145A155A148A149A158A151A144A148A149A150A156A155A158A149A145A151A144A144A149A155A156A155A158A149A155A151A155A149A155A156A159A160A159A161A157A158A146A149A145A151A148A147A149A145A151A148A149A144A154A146A148A149A152A151A144A144A149A153A146A144A149A150A151A144A145A149A155A158A150A149A146A151A150A149A150A156A146A145A149A158A151A162PG310G1701VSCONTROLG74ROG88PG17G13PG310G1705,G13G13PG310G1701VSMODELG74ROG88PG17表23G1838G1206G4002定程度G3176G1457应G2420MTFG1395大鼠肝脏的保G1817作用。G1206肝G4407指数G3176G2209，模型G1395照组的G2876均值G36094G171，MTF各处G2360组（剂量分别G36095、10和20MG74KG74A120A121DA120A121）分别G36094G170、3G17G25和3G172。G402710和20MG74KG74A120A121DA120A121剂量的MTF给药组的大鼠肝G4407指数明显低于模型组，且20MG74KG74A120A121DA120A121剂量组的大鼠肝G4407指数G4144G4350G1064G1395照组G2052G2093。G2454外，观察各组大鼠肝脏的外观，模型组大鼠肝脏G3480积明显G4249大，G4407量G4249G1958，表G2635G3661光G4246，G1103G3108白G3140，G871G2663G2085G4294，G936G4184G1402G4181，G4393G1305G941G3112，有G1825G2728G1579；而MTFG3244G3954组的大鼠肝脏的G3480积、G4407量、G3140G4246、G4393G1305均有明显G1567G3167，G4109其G326220MG74KG74A120A121DA120A121剂量组大鼠肝脏表G2635光G1825、G1103暗G1795G3140、G2052G2093G4350G1064组。G3176G3309结果G3476G3253，MTF能剂量G4007G2304性G1305降低大鼠的血脂G3331G2876，抵抗大鼠高脂血症的G3833G1102，并G4002定程度G3176G4167G1469脂G1467肝的G3833G1102。3讨论G3244G3954结果表明，桑叶总黄酮能显著抵抗TRITONWR1339诱导的小鼠血清TG，TC和LDLC等指标的升高，同时升高血清HDLC/TC和HDLC/LDLC的比值。数G2156G3476G3253MTF具有降低高脂血症小鼠血脂G3331G2876的G1891性，而且给药后12H作用效果更明显。喂高脂饲料的大鼠模型也同样表明MTF具有降低血脂的作用，而且具有剂量G4007G2304性。桑叶总黄酮降低血脂的机G4389，G2690前G3177G994清G1155，G1620G2156G3244G3954结果并结G1766G3635G3748G881G1281的G4002G3796黄酮G2347G1828G1766G3678G1336G2059血脂的G3535G2117，G3543测G4027G3727G4002G3796G3535G2117可能G3262MTF降血脂作用的机G4389。A135A125A136A137A144A145A145A125A127A139A140A141A155A149A145A144A153A149A146A156A163A160A159A161A157A135A125A136A137A144A145A145A125A127A161A144A141A158A150A149A146A151A144A145A149A158A158A153A149A155A151A146A149A148A154A158A153A149A153A151A155A149A147A158A155A149A148A151A144A158A149A147A146A145A149A146A151A144A147A149A153A158A148A149A144A151A152A149A147A164A123A129A165A166A130A143A136A167A133A135A136A141A147A150A146A149A150A151A158A158A149A148A147A155A148A149A145A151A146A147A149A145A147A155A145A149A147A151A146A148A149A146A147A150A148A149A148A151A158A155A149A153A147A148A152A149A144A151A153A155A149A144A147A155A155A149A144A151A158A150A149A145A163A168A169A153A149A147A151A145A149A147A158A149A144A151A145A149A153A154A158A149A145A151A145A149A146A153A149A148A151A145A149A147A156A153A149A147A151A145A149A153A156A156A153A149A147A151A145A149A153A156血清中的胆固醇G3278G3733G3985G4144脂G1467G3382结G1766G1102G7265，G1004能G900G4455G4206和G1245G3814。G2520G2432脂胆固醇G7263G1902G4455G4013G2589（LCG36T）G4110肝脏G1766G1102并分G2623G4384血清，能G1218G1828G2520G2432脂G552G3626的脂G7263G1902G4455G4013G4384G4115离胆固醇的3G7205G1902G3219G1102胆固醇脂，G3248血清中G4115离胆固醇G1992G3186，胆固醇G7265G4249G1958。血清中HDLC的含量能G4002定程度G3176G1457G4088G1147LCG36T的G1891性A170A171A172，G4057而可G4027G1206黄酮G2347G1828G1766G3678能升高HDLC/LDLC比值G3176，G3543测G1566G2347G1828G1766G3678能G1212G2089胆固醇向肝脏G4455G4206和G1245G3814A170A173A172。G4002G3796G4369G3678黄酮G4024G900G4355明能G1911G1891LCG36T，G1206而G1212G2089胆固醇G7265的G3219G1102，G1958G3374血清胆固醇的清G1154。G3649G2604的G3929G2126也G1439G3747，给予MTF的小鼠G1923大鼠血清中的HDLC/TC比值显著升高，HDLC/LDLC比值G2096G1685小鼠G305