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1、炎症介质与抗炎药物Inflammatorymediatorsandanti-inflammatorydrugs2014.10.9Inflammation(炎症）Theclassicalsignsofinflammationareredness,swelling,heat,pain,andlossoffunction.SkinabscessPneumoniaTheProcessofInflammation1.Initiationoftheeventbyaforeignsubstanceorphysic
2、alinjury2.Recruitmentandchemoattractionofinflammatorycells,andactivationofthesecells3.Releaseinflammatorymediatorscapableofdamagingorkillinganinvadingmicrobeortumor.Insomeinstances,theinflammatoryresponseisinitiatedbyanotherwiseharmlessforeignmaterial(
3、e.g.,pollen).Inflammationcanalsoresultfromanautoimmuneresponsetothehost’sowntissue,asoccursinrheumatoidarthritis.Whydoweneedanti-inflammatorydrugs?Inmostcases,theinflammatoryresponseeventuallysubsides,butifsuchaself-limitingregulationdoesnotoccur,thein
4、flammatoryresponsewillrequirepharmacologicalintervention.Theneedforanti-inflammatorydrugsariseswhentheinflammatoryresponseisinappropriate,aberrant,sustained,orcausesdestructionoftissue.Hosttissuemayundergoinjury,sincemanyoftheinflammatorymediatorsareno
5、tspecificforaparticulartissuetarget.THEINFLAMMATORYPROCESSEicosanoids类花生酸Theeicosanoids,derivedfroma20-carbonunsaturatedfattyacid,arachidonicacid(eicosatetraenoicacid),areobtainedfrommembranephospholipidsandsynthesizeddenovoatthetimeofcellularstimulati
6、on.ArachidonateMetabolismPathwaysPhospholipidsArachidonicAcidCOX-2COX-1Oldanti-inflammatorydrugtargetProstaglandinH2PGI2PGF2αPGE2PGD2TXA2PhospholipaseA2PGESPGES:prostaglandinEsynthase,anewanti-inflammatorydrugtargetPGDH15-keto-PGE2Cyclooxygenase(COX)Tw
7、oisoforms:COX-1：Constitutiveor“housekeeping”isoformthatisresponsibleforthebasalproductionofprostaglandins,prostacyclins,andthromboxanes.COX-2：Induciblebycytokinesandotherinflammatorystimuliandisbelievedtopredominateduringchronicinflammation.Thefinalpro
8、ductoftheCOXpathwayistissuespecific.Forexample,plateletsproducethromboxaneA2(TxA2);vascularendothelialcellsproduceprostacyclin(PGI2);mastcellsproduceprostaglandinD2(PGD2);COX-2selectiveinhibitorssuperiortonon-selectiveinhibitors?15-Pros
