乳酸对孕早期小鼠胎盘促血管生成基因表达及胎鼠生长的影响

金妮; 陈书强; 芦洁; 王晓红

doi:10.12435/j.issn.2095-5227.2024.116

乳酸对孕早期小鼠胎盘促血管生成基因表达及胎鼠生长的影响

Effects of lactic acid on expression of placental angiogenesis and fetal growth in mice during early pregnancy

摘要

摘要:
背景胚胎着床过程中，子宫内膜基质细胞发生蜕膜化，进一步支持妊娠。子宫内膜蜕膜化过程中存在Warburg样糖酵解，产生大量乳酸。
目的探讨乳酸对孕早期小鼠胎盘促血管生成基因表达及胎鼠生长的影响。
方法选择6 ~ 8周龄的CD1雌性小鼠，与雄鼠交配成功后，随机分为抑制剂组和对照组，每组12只。抑制剂组从小鼠孕4.5 d开始连续3 d给予腹腔注射Syrosingopine 乳酸转运体抑制剂，剂量为7.5 mg/(kg·d)；对照组单纯腹腔注射等体积的0.9%氯化钠注射液；于妊娠8.5 d取小鼠孕囊称重，RT-PCR检测小鼠蜕膜组织中促胎儿生长和促血管生成相关基因的表达；于妊娠12.5 d取胎鼠及胎盘称重，RT-PCR检测胎盘促血管生成相关基因的表达，Western blot检测胎盘中CD31蛋白表达的变化。
结果与对照组比较：孕8.5 d，抑制剂组小鼠孕囊组织重量降低(P＜0.001)，蜕膜组织中促胎儿生长/促血管生成相关基因Opn、Ogn、Angpt2、Angpt4、CD31、Hif-1α、Tgf-1β、Tie-2、Vegfr2、Vegfr3 的mRNA表达水平降低(P＜0.05)；孕12.5 d，抑制剂组胎鼠体质量降低(P=0.003)，胎盘重量降低(P=0.033)，胎盘效率降低(P＜0.001)，小鼠胎盘促血管生成相关基因Angpt4、CD31、Hif-1α、Tgf-1β、Tie-2、Vegfr2、Vegfr3的mRNA表达水平降低(P＜0.05)，小鼠胎盘组织的CD31蛋白表达水平降低(P＜0.05)。
结论抑制蜕膜组织乳酸摄取可降低孕早期小鼠胎盘促血管生成基因表达，可能对胎鼠生长产生影响。

Abstract:
Background Endometrial stromal cells undergo decidualization to further support pregnancy during implantation. Warburg-like glycolysis produces a large amount of lactic acid during decidualization.
Objective To investigate the effects of lactic acid and metabolism on expression of placental angiogenesis and fetal growth in mice during early pregnancy.
Methods CD1 female mice aged 6-8 weeks were selected in this study. Syrosingopine inhibitor (7.5 mg/kg·d) was injected daily intraperitoneally into pregnant mice from 4.5 days of gestation for 3 days (Sy group, n=12). Mice receiving normal saline treatment with an equal injection volume served as control group (NC group, n=12). The gestational sac of mice was weighed at 8.5 days of gestation, and the relative mRNA expression of fetal growth and angiogenesis in decidua tissues of mice was detected by RT-PCR. Fetus and placentas were weighed at 12.5 days of gestation. RT-PCR was used to detect the relative mRNA expression of the placental angiogenesis, and Western blot was used to detect the expression of CD31 protein in placenta.
Results Compared with the NC group, the weight of gestational sac at 8.5 days of gestation decreased significantly in the inhibitor group (P < 0.001). The expression levels of fetal growth and angiogenesis (Opn, Ogn, Angpt2, Angpt4, CD31, Hif-1α, Tgf-1β, Tie-2, Vegfr2 and Vegfr3) in decidua tissues also significantly decreased, and the differences were statistically significant (P < 0.05). The fetus weight (P=0.003), placental weight (P=0.033) and placental efficiency (P < 0.001) at 12.5 days of gestation in mice were decreased in inhibitor group; The mRNA expression levels of Angpt4, CD31, Hif-1α, Tgf-1β, Tie-2, Vegfr2 and Vegfr3 in placental angiogenesis decreased significantly in the inhibitor group (P < 0.05). The expression level of CD31 protein in placental tissue of mice significantly decreased in the inhibitor group (P < 0.05).
Conclusion Inhibition of lactic acid in vivo can reduce the expression of placental angiogenesis and fetal growth in mice during early pregnancy.

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