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叶绿素衍生物在预防感染引起的早产方面比孕激素更有效。

Chlorophyll Derivatives Exert Greater Potency Over Progesterone in the Prevention of Infection-Induced Preterm Birth in Murine Models.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Benin, Benin City, Edo State, Nigeria.

Cancer Innovation Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, USA.

出版信息

Am J Reprod Immunol. 2024 Oct;92(4):e70000. doi: 10.1111/aji.70000.

Abstract

PROBLEM

Preterm birth (PTB) is a significant cause of maternal and neonatal morbidity and mortality worldwide. However, the effectiveness of progesterone (P4) which is clinically used for PTB management remains controversial and necessitates research into new therapeutic options METHOD OF STUDY: In the current study, we investigated the effectiveness of two chlorophyll derivatives, pheophorbide a (PBa) and pheophytin a (PTa), in counteracting PTB. Timed-pregnant mice (gestation day 17 ± 0.5) received lipopolysaccharide (LPS) (25 µg/mouse) or phosphate-buffered saline (PBS) intraperitoneally, with PBa, PTa, progesterone (P4), and co-administration of P4 and ibuprofen (IBP), administered orally 2 h prior.

RESULTS

The LPS group experienced PTB and 100% fetal mortality, whereas the PBa and PTa groups showed a delayed onset of LPS-induced PTB, with significantly decreased PTB rate and fetal mortality. In addition, PBa and PTa suppressed LPS-induced pro-inflammatory cytokines and NF-κB transcription factor while increasing anti-inflammatory cytokines in the placenta and uterus.

CONCLUSIONS

Our findings indicate that the chlorophyll derivatives, PBa and PTa increase fetal survival in infection-induced PTB and demonstrate greater efficacy than P4 in preventing PTB.

摘要

问题

早产(PTB)是全球孕产妇和新生儿发病率和死亡率的重要原因。然而,临床上用于 PTB 管理的孕激素(P4)的有效性仍存在争议,需要研究新的治疗选择。

方法

在本研究中,我们研究了两种叶绿素衍生物,原卟啉 a(PBa)和叶绿酸 a(PTa)在对抗 PTB 中的有效性。定时怀孕的小鼠(妊娠第 17 天±0.5)经腹腔内给予脂多糖(LPS)(25μg/只)或磷酸盐缓冲盐水(PBS),并在 2 小时前口服给予 PBa、PTa、孕激素(P4)和 P4 与布洛芬(IBP)联合治疗。

结果

LPS 组发生 PTB 和 100%胎儿死亡,而 PBa 和 PTa 组则显示 LPS 诱导的 PTB 延迟发作,PTB 发生率和胎儿死亡率显著降低。此外,PBa 和 PTa 抑制了 LPS 诱导的促炎细胞因子和 NF-κB 转录因子,同时增加了胎盘和子宫中的抗炎细胞因子。

结论

我们的研究结果表明,叶绿素衍生物 PBa 和 PTa 增加了感染诱导的 PTB 中胎儿的存活率,并且在预防 PTB 方面比 P4 更有效。

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