[生物医药论文精品a]贞清方调节srebp-1c减少糖尿病大鼠肾脏脂质沉积

1贞清方调节SREBP1C减少糖尿病大鼠肾脏脂质沉积文秀英，A1许明旺，A2胡勤瑾，A4罗琼，A4鲁敏，A4（1华中科技大学同济医学院附属梨园医院中西医结合科，武汉430077；2华中科技大学同济医学院附属梨园医院老年医药学研究所；3华中科技大学同济医学院硕士研究生）摘要目的探讨贞清方对糖尿病大鼠肾脏脂质代谢的调节作用及其分子机制。方法高糖高脂饲料加低剂量链脲佐菌素注射制备2型糖尿病大鼠模型，将成模大鼠分为贞清方组、二甲双胍组、模型组，另设正常对照组，每组18只大鼠。分别在治疗8周和12周时检测大鼠的肾皮质TG含量。12周时，采用RTPCR检测肾皮质G3278G18267调节G1815G1226结合G15519G113451C（SREBP1C）和脂G13950G18252合成G18250（FAS）的MRNAG15932G17810，同时，检测G15892糖、G15892G10988G8845G989G18243（TG）、G5647G13978G3278G18267（TC）和尿G5506量G11345G15519G11345G6502G8856G10587UAE，肾脏G15904HEG7591G14406、在G1821G19248G991作肾组G13467G5430G5589学G16278G4531。结果8周时模型组肾皮质TG含量G7389G3698高的G17247G2195，G1306G994正常组G8616G17751G7092G7186G14891G5627G5058G5334P005，G1016治疗组的肾皮质TG含量G994正常组G8616G17751G7092明G7186G2476G2282。12周时，G994正常组G11468G8616，模型组大鼠肾皮质TG含量G7186G14891G2331高（P005ANDTHELEVELOFRENALTGSHOWEDNOOBVIOUSCHANGEINTWOTREATEDGROUPSATWEEK12,THERENALTGWASHIGHERINUNTREATEDMODELRATSCOMPAREDWITHCONTROLP005，G1016治疗组的肾皮质TG含量G994正常组G8616G17751G7092明G7186G2476G2282。12周时，模型组大鼠肾皮质TG含量G7186G14891G2331高（P001）,二甲双胍组和贞清方组肾皮质TG含量G17751模型组明G7186G1955G4581（P001）。A84A85A86A87A88A89A90A91A92A93A94A95A96A97A98A99A100A101A102SXA102A103A104A105A106A107A107A103A104A108A109A110A111A112A113A114A109A115A115A116A112TAB2CHANGESOFRENALTGCONTENTSINRATSATDIFFERENTTIMECOURSEOFTREATMENT,SXA117A118A119A120A121A122A122A118A119A123A124A125A126A127A128A129A124A130A130A131A127NWEEK8TGWEEK12NTGCONTROL6015400631101690057MODEL60189007410029400871METFORMIN60150005911020100792ZQR60162006111019500752A132A133A134A135A136A137A138A1391P001A140A134A141A142A137A138A1392P001NOTECOMPAREDWITHCONTROLGROUP,1P001A140COMPAREDWITHMODELGROUP,2P00145肾皮质SREBP1C和FASMRNA的G15932G17810模型组SREBP1C和FASMRNA的G15932G17810G7186G14891高G1122正常组（P001）。G994模型组G8616G17751，贞清方组SREBP1CMRNA的G15932G17810G19762常G7186G14891G991调（P001），二甲双胍组的SREBP1CMRNAG15932G17810G1146G7186G14891G991调（P001），G1306仍高G1122正常组（P005）。贞清方组和二甲双胍组的FASMRNAG15932G17810G3355G7186G14891低G1122模型组（P001），见G159323、图3。9A143A144贞清方对A145A146A147A148A149SREBP1CA150FASMRNAA151A152A153A154A155A156SXTAB3EFFECTSOFZQRONSREBP1CANDFASMRNALEVELINRATSKIDNEY,SXNSREBP1CFASCONTROL1103081570037MODEL100581A157006620489A15700512METFORMIN110362A1570050130308A15700453ZQR110326A157005430315A15700483A158A159A160A161A162A163A164A165P005A166P001A167A160A168A169A163A164A165P001NOTECOMPAREDWITHCONTROLGROUP,1P001,2P001A167COMPAREDWITHMODELGROUP,3P001ABCDMARKERA1703A171A172A173A174A175A171A172A173A174SREBP1CA176FASMRNAA177A178SREBP1CA179191BPA180FASA179397BPA180A181ACTINA179589BPA182AA183A184A185A180BA186A187A185A180CA188A189A190A191A185A180DA192A193A194A185A182FIG3SREBP1CANDFASMRNAEXPRESSIONINRATSKIDNEYSREBP1CA179191BPA180FASA179397BPA180A181ACTINA179589BPA182ACONTROLBMODELCMETFORMINDZQR5讨论100BP200BP300BP400BP500BP600BPA195ACTINSREBP1CFAS100BP200BP300BP400BP500BP600BP100BP200BP300BP400BP500BP600BP10本实验用高糖高脂加G4579剂量SG55Z制备了2型糖尿病大鼠模型，G1122G17908模成G2163G2530的G12544G27周检测G2520组中部分大鼠的肾组G13467G55G42含量，模型组肾G55G42G7389G3698高的G17247G2195，G1306G994正常组G8616G17751G7092G7186G14891G5627G5058G5334，说明在G27周时肾脏的脂质G8797G12227不严G18337。G17908模成G2163G2530的G1254412周模型组肾组G13467G55G42含量G7186G14891G3698高。模型组大鼠的肾脏病G10714学检查G2499见肾G4579G10711G13007G14192G13466G14002和G13466G14002G3818G3534质G3698生，G3534底G14192G3698厚，肾G4579G10711节段G5627G11840G2282；肾G4579G12661G990皮G13466G14002G1998G10628G18337度脂G13950G2476G5627和水G7691G2476G5627。这说明G19555G11540G17908模的时G19400延长，肾脏G1998G10628了脂质G6451害的特征，脂质代谢G5334常是肾脏病G2476G17839展的部分原G3252。脂代谢G5334常G5353G17227糖尿病肾病的分子机制目前认为G994SREBPG161G70介G4560G55G42在肾脏G8797G12227、G5353G17227肾脏G6451害G7389关。SREBPG161G70G11464G6521调节G41ASG3534G3252的G15932G17810，G41ASG17902G17819催G2282乙酰辅G18250A和丙二酰辅G18250A而合成长链脂G13950G18252，以G55G42的G5430式G4396储16,17。G7389研究G15932明G2345纯高糖高脂饲养的C57BL/6JG4579鼠16和G2345纯STZ注射的1型糖尿病大鼠1，G3355G1998G10628SREBP1C和FAS高G15932G17810和肾组G13467TG含量G3698高。本实验对大鼠喂以高糖高脂饲料加G990G4579剂量STZ注射G5326G12447模型，结G7536G15932明SREBPG161G70和G41ASMRNA在模型组大鼠肾组G13467高G15932G17810，这G994模型组肾脏G1998G10628的脂质G6451害G7389关。我们的工作G2469G10628在G17908模的G1254412周G1998G10628明G7186的肾脏脂质G8797G12227，这对G2530人利用此模型来研究糖尿病肾脏脂质代谢的情况奠G4462了G3534础。调节SREBP1C的G15932G17810G2499G1955G4581脂质对肾脏的G6451害，敲G19512G4579鼠的SREBPG161G70G3534G3252，G2499防止G4579鼠由G1122高脂饮食所G14280的肾脏G55G42G41G16G163、PAG44G161和G57EG42G41G15932G17810的G3698G5390以及G13466G14002G3818G3534质的聚G1222718，G1146G2499防止G4579鼠由G1122SG55Z注射所G14280的G15519G11345尿12。G7389学G13785用二甲双胍治疗脂G13950G13937，G2469G10628二甲双胍G2499G19489低SREBP1CMRNA及G15519G11345G15932G17810G15从而G6925G2904G13937脏脂G13950G2476G562719。本实验G16278G4531贞清方对2型糖尿病大鼠肾脏脂质代谢的影响，研究G2469G10628贞清方G14033G991调SREBPG161G70MRNA和G41ASMRNA的G15932G17810，G1955G4581肾组G13467G55G42含量，同时，采用二甲双胍作为对照用药，结G7536G7186示二甲双胍也G7389G11468G1296的G6940G7536。G1016药G3355G14033G19489G19489低G15892糖和G15892脂，G6925G2904肾脏的病G10714G6451G1272，G1955G4581尿G5506量G11345G15519G11345的G6502G8856。以SREBPG161G70及其G991G9228G3534G3252作为靶G9869来研究中药治疗糖尿病肾病的药G6940机制G7389G17751G3921的应用前G7235，值得G9157入探讨。REFERENCES1SUNL,HALAIHELN,ZHANGW,ETALROLEOFSTEROLREGULATORYELEMENTBINDINGPROTEIN1INREGULATIONOFRENALLIPIDMETABOLISMANDGLOMERULOSCLEROSISINDIABETESMELLIT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