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目的:研究脂多糖(LPS)诱发同基因妊娠BALB/c小鼠和非肥胖性糖尿病/重度联合免疫缺陷(NOD/SCID)小鼠早产的机制。方法:在预先阻断或未阻断Toll样受体4(TLR4)的条件下采用LPS刺激,并比较各组BALB/c和NOD/SCID小鼠的早产率和胚胎死亡率。由于预实验显示预期的早产均发生于孕16d,因此,实验中在早产发生之前处死小鼠,收集每只孕鼠的胎盘。采用流式细胞术检测胎盘CD45+细胞表面TLR4、CD80和细胞内TNF-α的表达率。结果:采用LPS可诱发BALB/c小鼠早产,而NOD/SCID小鼠则对LPS的诱导有抵抗。经LPS刺激后,TLR4的表达在BALB/c和NOD/SCID小鼠均无显著改变,但是两组小鼠CD45+CD80+细胞的百分率均升高。相反,LPS刺激后仅BALB/c小鼠CD45+TNF-α+细胞的百分率升高,而NOD/SCID小鼠则否。通过预先阻断TLR4的表达可消除LPS对BALB/c小鼠CD80和TNF-α表达的影响,并显著降低LPS诱发的早产率。结论:虽然LPS未能改变TLR4的表达,但是二者相互作用,可激发CD45+CD80+细胞的动员,导致炎性细胞因子产生增多,并最终导致早产。BALB/c和NOD/SCID小鼠对LPS刺激的敏感性存在差异,提示NOD/SCID小鼠缺乏功能正常的T细胞和NK细胞,可能是这种小鼠对LPS诱发的早产有抵抗的原因之一。
OBJECTIVE: To investigate the mechanism of lipopolysaccharide (LPS) premature delivery in syngenic pregnant BALB / c mice and non-obese diabetic / severe combined immunodeficiency (NOD / SCID) mice. METHODS: LPS stimulation was performed with or without blocking Toll-like Receptor 4 (TLR4), and the preterm birth rate and embryo mortality of BALB / c and NOD / SCID mice in each group were compared. Since pre-experiments showed that the expected preterm birth occurred on the 16th day of pregnancy, mice were sacrificed in the experiment before the preterm birth, and the placenta of each pregnant rat was collected. Flow cytometry was used to detect the expression of TLR4, CD80 and the level of intracellular TNF-α on placental CD45 + cells. RESULTS: Premature delivery of BALB / c mice was induced by LPS, whereas NOD / SCID mice were resistant to LPS induction. After LPS stimulation, the expression of TLR4 did not change significantly in BALB / c and NOD / SCID mice, but the percentage of CD45 + CD80 + cells in both groups increased. In contrast, only the percentage of CD45 + TNF- [alpha] + cells in BALB / c mice increased after LPS stimulation compared to NOD / SCID mice. By blocking the expression of TLR4 in advance, the effect of LPS on the expression of CD80 and TNF-α in BALB / c mice can be eliminated and the LPS-induced preterm birth rate can be significantly reduced. CONCLUSION: Although LPS does not alter the expression of TLR4, the interaction between the two can stimulate the mobilization of CD45 + CD80 + cells, leading to increased production of inflammatory cytokines and eventually to premature delivery. The sensitivity of BALB / c and NOD / SCID mice to LPS stimulation varied, suggesting that NOD / SCID mice lacking normally functioning T and NK cells may be responsible for the resistance of this mouse to LPS-induced preterm birth one.