TLR4受体在妊娠期缺氧子代大鼠动脉粥样硬化的研究

Research on Toll-like Receptors 4 with Atherosclerosis with Offspring Rats from Hypoxia During Pregnancy

目的:在妊娠期缺氧子代SD大鼠应用脂多糖,以研究TLR4受体在动脉粥样硬化中的作用。方法:将20只鼠龄8月妊娠期缺氧雄性子代大鼠分为两组(G2)和(G4),每组10只,分别给予腹腔注射生理盐水(等容积)或脂多糖(2.5 mg/kg),将20只妊娠期缺氧空白对照雄性子代大鼠(G1)和(G3)作相应处理,每周2次,连续注射8周。于12月龄后处死大鼠。采用ELISA检测大鼠血清中炎症相关因子IFN-γ、TNF-α、IL-1β的水平,Real time-PCR检测大鼠主动脉组织中NF-κB p65与TLR4m RNA表达。结果:G3和G4组炎症相关因子IFN-γ、TNF-α、IL-1β水平升高(P<0.05),主动脉组织中TLR4、NF-κBp65 mRNA的表达明显升高(P<0.05),并且G4最高(P<0.05)。结论脂多糖可以引起主动脉炎症反应。通过TLR4/NF-κB信号途径的激活,TLR4受体在动脉粥样硬化中起到了重要的作用。

Objective:To investigate the pathologic mechanisms of TLR4 in atherosclerosis after TLR4 agonists(LPS)were administered to offspring rats from hypoxia during pregnancy.Method:Twenty female offspring rats from hypoxia during pregnancy aged 8 months were randomized into two groups(G2)and(G4)with 10 in each group.Saline(isovolumic normal saline)and LPS(2.5 mg/kg)were administered respectively by intraperitoneal injection,twice a week.Corresponding interventions were given to offspring rats(G1)and(G3),from control group during pregnancy and compared with offspring rats from hypoxia during pregnancy.After treatment 8 weeks,the ELISA was used to measure the IFN-γ,TNF-α,IL-1βof serologic inflammatory cytokines,and the real time-PCR was used to measure the TLR4 and NF-κB p65 mRNA expressions in aortic sinus specimens aortic sinus.Result:The levels of immune inflammatory mediators(IFN-γ,TNF-α,IL-1β)rose significantly in group G3 and G4(P<0.05).Simultaneously,TLR4 and NF-κB p65 mRNA expressions in the aorta tissue of group G3 and G4 were enhanced(P<0.05).In addition,the above-mentioned parameters were more obvious in group G4(P<0.05).Conclusion:Inflammatory response occurred in the aorta tissue in rats after LPS exposure.TLR4 receptor revealed an important role in inflammatory injury of the aorta tissue after LPS stimulation by the activation of TLR4/NF-κB signal pathway.