六甲基杨梅素的合成及其对hkv1 5通道的影响与国产fgf 21对kkay和obob小鼠的作用-synthesis of hexamethylmyricetin and its influence on hk v1 5 channel and the effect of domestic fgf 21 on kkay and obob mice.docxVIP

33.6±2.0%（n=4）。通过拟合计算，HMM抑制IKur的IC50为1.79μM。结论：HMM对hKv1.5通道有较强的抑制作用。关键词：Kv1.5；IKur；房颤第三部分国产FGF-21对KKAy和ob/ob小鼠的作用目的：研究国产FGF-21对KKAy和ob/ob小鼠的作用。方法：①KKAy小鼠单笼喂养，给予高脂饲料；ob/ob小鼠每笼5只饲养，给予普通饲料；控制室温23±2℃，湿度50%，明暗周期12h（7:00-19:00），自由进食饮水。②用眼科剪在KKAy、ob/ob小鼠脚趾剪一小口，全血渗出足量后（约0.6μl，仪器最低需样量），使用罗氏血糖仪检测血糖，记录血糖值及采血时间。③口服糖耐量试验（OGTT，oralglucosetolerancetest）。小鼠禁食2h后，测0min血糖，灌胃给予2g/kg的葡萄糖溶液，分别于给予葡萄糖溶液后30min、60min、120min检测血糖。结果：①KKAy小鼠对受试样品FGF-21不敏感；②FGF-21低剂量（0.6mg/kg/d）对ob/ob小鼠空腹血糖具有一定的降低作用，但无统计学差异；FGF-21高剂量（2.5mg/kg/d）对ob/ob小鼠餐后血糖具有降低作用，连续给药7天后，降糖作用显示统计学差异；③OGTT结果显示，FGF-21低剂量（0.6mg/kg/d）对ob/ob小鼠具有适度的改善糖耐量受损的作用。结论：国产FGF-21具有一定的抗糖尿病作用，主要表现为降低餐后血糖，改善糖耐量受损。与文献相比，国产FGF-21效价只有Lilly公司的1/10，建议厂家改善工艺。关键词：FGF-21；KKAy；ob/ob；糖尿病；肥胖AbstractPartIThesynthesisofHexamethylmyricetinAim：Toinvestigateamoreefficientmethodofthesynthesisandpurationofhexamethylmyricetin(HMM),meanwhile,todevelopaspecificandsensitiveHPLCdetectionmethod.Methods:HMMwassynthesizedbymethylationofmyricetinusingMe2SO4asmethylationreagent.Thereactionprocesswasalsofurtheroptimizedbythefactorsofreactantratio,temperatureandreactiontime.Afterreactionstarted,samplesweretakenatdifferenttimepoints.TheultravioletabsorptionofthemixturewasdetectedbyHPLCtojudgetheprogressofreaction.Attheendofthereaction,thesolventwasseparatedandarawsolidproductformed.Thenwashthesolidmixturewithwaterandrecrystlizewithalcohol.TheproductstructureconfigurationwasidentifiedbyMS,1HNMR,13CNMRandthencomparedwithformerlyreporteddata.Result:①TheproductwasconfirmedasHMMbyMS,1HNMR,13CNMR;②SynthesisofHMMbytheoptimizedprocessgaveaproductof53%finalyieldandpurity≥98.84%(HPLCarea%).③Theoptimizedreactionconditions:theidealreactantratio,temperatureandreactiontimeare1:7:9(myricetin∶Me2SO4∶K2CO3),50℃and9hours,respectively.Conclusion:Themodifiedprocedureofsynthesiswasconvenient,economicalandproducedlesspollution.OptimizedreactionconditionscouldpromiseahighyieldandpurityofHMMproduct.Keywords:myricetin;Me2SO4;methlation;flaovnoidsPartⅡEffectsofHMMonthehKv1.5channelinHEK293cellAim:Toin