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1、鹽酸氯丙嗪對(duì)Caco-2細(xì)胞膜流動(dòng)性的影響楊丹，王章陽(yáng)*（第三軍醫(yī)大學(xué)西南醫(yī)院藥學(xué)部重慶400038）摘要：目的考察鹽酸氯丙嗪對(duì)Caco-2細(xì)胞膜流動(dòng)性的影響，了解其促進(jìn)藥物直腸吸收的可能機(jī)理。方法采用3組不同濃度的鹽酸氯丙嗪對(duì)Caco-2細(xì)胞作用不同時(shí)間后，測(cè)定細(xì)胞膜脂質(zhì)熒光探針DPH的熒光強(qiáng)度，通過(guò)計(jì)算熒光偏振度Pr，對(duì)細(xì)胞膜流動(dòng)性的變化進(jìn)行評(píng)價(jià)。結(jié)果與對(duì)照組比較，鹽酸氯丙嗪與Caco-2細(xì)胞作用15min后，膜脂質(zhì)熒光偏振度Pr迅速降低，并隨著鹽酸氯丙嗪濃度的增高及作用時(shí)間的延長(zhǎng)，Pr呈現(xiàn)逐漸下降的趨勢(shì)；但在鹽
2、酸氯丙嗪濃度低于56μmol·L-1，作用時(shí)間少于30min時(shí)，Pr的變化不明顯（P>0.05）。當(dāng)作用濃度同為112μmol·L-1時(shí)，鹽酸氯丙嗪溶液與Caco-2細(xì)胞作用15min時(shí)Pr明顯低于作用時(shí)間為60min和120min時(shí)的Pr（P<0.05）；但在鹽酸氯丙嗪濃度低于112μmol·L-1時(shí)，無(wú)論作用時(shí)間的長(zhǎng)短，Pr未觀察到明顯差異。當(dāng)鹽酸氯丙嗪作用濃度相同時(shí)，不同的作用時(shí)間與Pr之間存在顯著性負(fù)相關(guān)，隨著作用時(shí)間的增加Pr逐漸降低(P<0.05)。結(jié)論鹽酸氯丙嗪可增加Caco-2細(xì)胞膜脂質(zhì)流動(dòng)性，隨著鹽
3、酸氯丙嗪濃度的增大以及作用時(shí)間的延長(zhǎng)，膜的流動(dòng)性會(huì)逐漸增加。因此，增加細(xì)胞膜脂質(zhì)流動(dòng)性，使細(xì)胞質(zhì)膜間隙增大、膜通透性增加是鹽酸氯丙嗪促進(jìn)藥物直腸吸收的可能機(jī)制之一。關(guān)鍵詞鹽酸氯丙嗪；膜流動(dòng)性；Caco-2細(xì)胞EffectsofChlorpromazineHydrochlorideonlipidfluidityofCaco-2cellmembraneYANGDan，WANGZhang-yang*（DepartmentofPharmacy,TheAffiliatedSouthwestHospitalofThirdMili
4、taryMedicalUniversity,Chongqing400038,China）Abstract：ObjectiveTheeffectsofChlorpromazineHydrochlorideonlipidfluidityofCaco-2（thehumancolonadenocarcinomacelllines）cellmembranewasstudied.MethodsAftertheCaco-2cellsweretreatedwithdifferentconcentrationofChlorpromaz
5、ineHydrochloridefordifferentduration,thefluorescentintensitywasdeterminatedbyfluorescencespectrophotometerwith1,6-diphenyl-1,3,5-hexatriene(DPH)asafluoresceinmark,thustocalculatethefluorescencepolarization(Pr)ofCaco-2cellmembraneaccordingtothespecificformulawit
6、hfluorescentintensitydata.ResultsComparedwiththenormalcontrol,decreaseofthefluorescencepolarization(Pr)ofCaco-2cellmembranewasobservedaftertheCaco-2cellsweretreatedwithChlorpromazineHydrochlorideformorethan15min,andPrvaluedecreaseswithChlorpromazineHydrochlorid
7、econcentrationincreased.WhenChlorpromazineHydrochloridewaslessthan56μmol·L-1forlessthan30min,PrvalueofCaco-2cellmembranehadnosignificantdifferencecomparedtocontrol(P>0.05).AndPrvalueunder112μmol·L-1ChlorpromazineHydrochloridehadsignificantdifferencesbetweenacti
8、ontimeof15minandactiontimeof60minor120min(P<0.05).AsignificantnegativecorrelationswerefoundbetweenPrvalueanddurationatthesameconcentrationgroups（P<0.05）.ConclusionLipidfluid
