NF-κB信号通路通过影响子宫trNK细胞募集致小鼠子代生长受限

NF-κB signaling pathway impairs fetal growth in mice by regulating recruitment of uterine trNK cells

  • 摘要: 背景 核因子κB(Nuclear Factor kappa-B,NF-κB)通路参与调节趋化因子、炎症性细胞因子和基质金属蛋白酶的 表达,并且在蜕膜化和胚胎植入阶段发挥重要作用。目的 探讨NF-κB活性对小鼠子代生长的影响及可能机制。方法 32 只ICR小鼠随机分为两组,均自然妊娠,实验组于妊娠5.5 ~ 7.5 d给予腹腔注射溶于PBS的NF-κB抑制剂,对照组同期给予 腹腔注射相同体积PBS,两组于妊娠8.5 d各选10只取孕囊称重,于妊娠14.5 d每组取6只胎鼠及胎盘称重并计算胎盘效率 (胎鼠重量/胎盘重量)。采用免疫组化技术检测NF-κB抑制剂对小鼠子宫trNK细胞数量的影响,采用Real time PCR技术检测 蜕膜中与NK细胞募集和分化相关的趋化因子、细胞因子的表达。结果 实验组小鼠妊娠8.5 d孕囊重量低于对照组(P< 0.001),妊娠14.5 d胎鼠(P<0.001)及胎盘重量(P<0.05)、胎盘效率(P<0.01)均低于对照组。实验组小鼠妊娠8.5 d子宫trNK 细胞密度(阳性细胞数占总细胞数的比例)低于对照组(P<0.001)。实验组小鼠蜕膜趋化因子、细胞因子表达水平也低于对照 组,差异有统计学意义(P<0.05)。结论 抑制NF-κB活性可以降低小鼠蜕膜中趋化因子、细胞因子的表达,进而影响子宫 trNK细胞的募集与分化,导致子代生长受限。

     

    Abstract: Background The nuclear factor kappa-B (NF-κB) pathway is involved in regulating the expression of chemokines, inflammatory cytokines and matrix metalloproteinases, and plays an important role in decidualization and embryo implantation. Objective To investigate the effects of NF-κB activity on the growth of mouse and its possible mechanism.Methods Thirty-two ICR mice were randomly divided into two groups, all of which underwent natural pregnancy. The experimental group received intraperitoneal injections of NF-KB inhibitor dissolved in PBS from gestational days 5.5 to 7.5, while the control group received intraperitoneal injections of the same volume of PBS during the same period. The conceptuses of the two groups were weighed at 8.5 days of gestation (n=10). On day 14.5 (n=6), the weight of offspring and placentas were weighed and placental efficiency (placenta weight/fetal weight) was calculated. Immunohistochemistry was used to detect the effect of NF-κB inhibitor on the number of trNK cells in the uterus of mice. Real time PCR was used to detect the expression of chemokines and cytokines related to NK cell recruitment and differentiation in the decidua. Results NF- κB inhibitor administration significantly reduced the weights of implantation sites at gestation day 8.5 (P<0.001), as well as fetal weight (P<0.001), placental weight (P<0.05), and placental efficiency (P<0.01) at gestation day 14.5. At gestation day 8.5, APDC-treated mice exhibited a significantly reduced density of uterine trNK cells (proportion of immunopositive cells; P<0.001). Furthermore, APDC treatment significantly decreased the expression levels of decidual chemokines and cytokines (P<0.05). Conclusion Inhibition of NF- κB activity can reduce the expression of chemokines and cytokines in the decidua of mice, and then affect the recruitment and differentiation of uterine trNK cells, resulting in growth restriction of offspring.

     

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