利奈唑胺联用血必净通过抑制HIa-NLRP3通路减轻MRSA肺炎小鼠的炎症损伤

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Abstract：ObjectiveToevaluate thesynergisticprotectiveefectof inezolid（LZD）combined withXuebijingInjection （BJ，a traditionalChinesemedicineinjection）againstpneumoniacausedbymethicilin-resistantStaphylococcusaureus （MRSA）in miceandexploretheunderlyingmechanism.MethodsFiftyC57BL/6Jmicewith pneumoniainducedbytracheal instilation of MRSA were randomized equally into model group，low-andhigh-dose XBJ treatment groups （13and 80mg⋅kg-1⋅d-1 respectively），and combined treatment groupswith low-and high-dose XBJ （6.5 and 13mL⋅kg-1⋅d-1. ，respectively） and LZD（80 mg：kg1·d），with10treatedmiceasthenoralontrolgroup.Themiimumibitoryconcentration （MC）of Jand LZDagainstMRSAandtheirefectsonbacterialgrowthandhemolyticactivitywereasessedinvitro.Afterthetreatments， lungpathologiesofthemicewereobservedwithHEstaining，andIL-6，NF- α⋅ IL-1β，and IL-18levelsinlunghomogenate weremeasuredusingEISA;themRNAandproteinexpresionsofHla，NRP3，caspase-1andASCweredetectedusing qPCRand Western bloting，andpulmonary expressionsof NLRP3，caspase-1，and ASC were examined with immunohistochemistry.ResultsThecombined treatment withLZDandXBJ significantlyimproved survivalratesof the mousemodels，educedinflammatorycell infiltrationandlunginjuryscores，decreasedthelevelsofIL-6，NF- α IL-1β，and IL18，anddoweguatedmndpoteexprsiosofHa3cspse1ndAC.oesoedcteal activity against MRSA but inhibited α -hemolysin （Hla） secretion bothinvitroand in vivo to suppressNLRP3-mediated inflammation，whileLZDdidnotproducethiseffect.ConclusionLZDcombinedwithXBJproducesenhancedefcacyfor improving MRSApneumoniaposiblydueto XBJ-inducedinhibitionofNLRP3-mediated inflammatoryresponsevia inhibiting α -hemolysinsecretion.

Keywords：XuebijingInjection;linezolid;methiclln-resistantstaphylococcusaureus;pneumonia;NP3inflamasome; α -hemolysin

金黄色葡萄球菌，俗称金葡菌，作为常见食源性致病菌广泛定植于皮肤黏膜及开放性创面。（剩余17334字）