制何首乌对大鼠肝脏p450酶5种亚型mrna表达的影响

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1、制何首乌对大鼠肝脏P450酶5种亚型mRNA表达的影响　　[摘要]考察制何首?跛?提物作用后大鼠肝脏P450酶5种亚型的mRNA表达变化。SD大鼠随机分为正常对照组、制何首乌高、低剂量组（540，108g?kg-1），连续灌胃给药7d。给药结束后，检测大鼠血清生化指标，并采用实时荧光定量PCR测定各实验组大鼠肝脏P450酶5种亚型mRNA表达。实验结果显示AST在高、低剂量组都显著下降；ALT在低剂量组显著降低，在高剂量组显著升高。高、低剂量组的大鼠肝组织P450酶5种亚型mRNA的表达均下调，且下调程度与给药剂量成一定的剂量性依赖。特别是高剂量制何首乌水提物能够显著抑制大鼠的C

2、YP1A2和CYP2E1的mRNA表达。该研究发现大剂量制何首乌水提物具有肝毒性，且随着剂量增加其肝损伤程度增加。其中制何首乌水提物540g?kg-1对大鼠肝CYP1A2和CYP2E1的mRNA的表达有明显抑制作用。　　[关键词]制何首乌水提物；肝损伤；P450酶；血清生化指标；mRNA表达　　EffectofprocessedPolygonummultiflorumonmRNA　　expressionleveloffivesubtypesofCYP450enzymesinratliver　　HUANGChunlian1，2，FANXuemei2*，LIQian3，WANGYim

3、ing2，WANGShumei1，GONGMengjuan1*，LUOGuoan1，2　　（1SchoolofTraditionalChineseMedicine，GuangdongPharmaceuticalUniversity，Guangzhou510006，China；　　2DepartmentofChemistry，TsinghuaUniversity，Beijing100084，China；　　3GuangzhouConsunPharmaceuticalCo，Ltd，Guangzhou510610，China）　　[Abstract]Toobservetheeffect

4、ofprocessedPolygonummultiflorumonmRNAexpressionlevelsoffivesubtypesofCYP450enzymesinratliverSDratswererandomlydividedintothenormalcontrolgroup，processedPmultiflorumhighdoseandlowdosegroups（540g?kg-1and108g?kg-1）TheratsinadministrationgroupswerecontinuouslygivenwithprocessedPmutiflorumfor7days

5、byigadministration，andtheratsinnormalcontrolgroupweregivenwiththesamevolumeofdistilledwaterAftersuccessiveadministrationof7days，theserumbiochemicalindicationsweredetected，andRealtimequantitativePCRtechnologywasusedtodetectthemRNAexpressionlevelsoffivesubtypesofCYP450enzymesinratliverExperimen

6、talresultsshowedthatASTwasdecreasedsignificantlyinbothlowandhighdosegroupsALTwassignificantlydecreasedinlowdosegroupandsignificantlyincreasedinhighdosegroupThemRNAexpressionlevelsoffivesubtypesofCYP450enzymesinratliverweredecreasedinhighdoseandlowdosegroupsinadosedependentmannerEspeciallytheh

7、ighdoseprocessedPmultiflorumcouldsignificantlyinhibitCYP1A2andCYP2E1mRNAexpressionlevelsinratsThestudyshowedthathighdosePmultiflorumwaterextracthadhepatotoxicity，andthedegreeofliverdamagewasincreasedwiththeincreaseofdoseItshallbenotedthat540g