人参二醇皂苷对失血性休克-内毒素二次打击大鼠肺组织TLR4与IL-18表达的影响

目的观察失血性休克复合内毒素二次打击所致急性肺损伤(ALI)大鼠肺组织Toll样受体4(TLR4)及白介素-18(IL-18)表达的变化,探讨TLR4与IL-18在ALI中的作用以及人参二醇皂苷(PDS)和地塞米松(Dex)对其影响。方法利用失血性休克对Wistar大鼠制造第一次打击,之后给予地塞米松(Dex)或人参二醇皂苷(PDS)治疗,再腹腔注入脂多糖(LPS)作为第二次打击。二次打击6h后处死动物,取肺组织,通过RT-PCR检测TLR4和IL-18 mRNA,通过Western blot检测IL-18蛋白的表达。结果与假手术对照组相比,二次打击可使肺组织TLR4 mRNA、IL-18 mR-NA及IL-18蛋白表达水平明显升高(均P<0.01),而Dex或PDS预治疗则能显著降低其含量(P<0.05)。结论失血性休克-内毒素二次打击所致急性肺损伤可能通过增加TLR4功能从而使其介导的信号转导作用加强,导致IL-18等炎症介质的分泌增加引起肺损伤,而PDS通过抑制TLR4介导的信号转导通路,减少IL-18等炎性介质的释放从而减轻肺损伤。

The effect of panaxadiol saponin on the expressions of TLR4 and IL-18 in lung tissues of rats with acute lung injury induced by hemorrhagic shock-endotoxin two-hit

Objective To observe the changes in the expressions of Toll like receptor (TLR) 4 and IL-18 in lung tissues of acute lung injury (ALI) induced by hemorrhage-LPS two-hit to investigate the effect of TLR4 and IL-18 in ALI and the effects of dexamethasone and panaxadiol saponins (PDS).Methods Forty Wistar rats were divided randomly into sham operational group, two-hit group with hemorrhage-lipopolysaccharides (HL group), dexamethasone preventive therapy, PDS preventive therapy groups. The rats with first-hit by hemorrhagic shock were treated dexamethasone and panaxadiol saponins, then injected intraperitoneally lipopolysaccharide (LPS) as the second hit. The rats were killed 6 h after two-hit to obtain lung tissue to determine TLR4 and IL-18 mRNA expressions by RT-PCR and IL-18 protein expression by Western blot.Results TLR4 and IL-18 mRNA and IL-18 protein expressions in lung tissue after two-hit were higher than those in sham operation group (all P<0.01), but were obviously reduced by dexamethasone and PDS injections (P<0.05).Conclusions The mechanism of ALI induced by hemorrhage-LPS two-hit is to increase the mediators of inflammation secretion, such as IL-8 etc. through enhancing TLR4 function to promote the induced signal transduction. PDS injection could block the TLR4 induced signal transduction pathway and decrease the expressions of the IL-18 to lessen the lung damage.