Egg white-derived peptides decreased blood pressure via the competing endogenous RNA regulatory networks in female spontaneously hypertensive rats

Despite numerous studies reporting the effects and mechanisms of antihypertensive peptides including peptides derived from egg white proteins, the role of peptides in female hypertensive animal model is unknown. On the other hand, the role of epigenetic modulation by the peptide treatment has been rarely investigated. This study sought to investigate the effect of egg white protein hydrolysate (EWH) in female spontaneously hypertensive rats (SHRs) as well as to explore the underlying mechanisms from the perspectives of transcriptome and the profiles of non-coding RNAs. Young (12-14-week-old) female SHRs were orally administered with 250 mg/kg body weight (low-dose) or 1000 mg/kg body weight (high-dose) of EWH daily for 10 weeks. Blood pressure of the rats were monitored weekly. The miRNA in the aorta were profiled by the high-throughput RNA-seq technique. Differentially expressed (DE) RNAs in the aorta were identified for the construction of the competing endogenous RNA (ceRNA) networks and key molecules were validated by qRT-PCR. The treatment of the high-dose EWH showed a significant effect in reducing blood pressure in female SHRs. Bioinformatic analyses revealed 90 DE-miRNAs.尽管已有诸多研究报道了降压肽（antihypertensive peptides）包括卵清蛋白来源肽的作用与机制，但此类肽类在雌性高血压动物模型中的作用仍不明晰。此外，肽类治疗介导的表观遗传调控作用也极少被探究。本研究旨在探究卵清蛋白水解物（egg white protein hydrolysate, EWH）对雌性自发性高血压大鼠（spontaneously hypertensive rats, SHRs）的干预效果，并从转录组与非编码RNA（non-coding RNAs）谱的角度探索其潜在作用机制。选取12~14周龄的雌性SHRs，每日分别以250 mg/kg体重（低剂量组）与1000 mg/kg体重（高剂量组）的EWH灌胃给药，持续10周。每周监测大鼠血压水平。采用高通量RNA测序（high-throughput RNA-seq）技术对主动脉中的微小RNA（miRNA）进行表达谱分析。鉴定主动脉组织中的差异表达（DE）RNA，以此构建内源竞争RNA（ceRNA）网络，并通过实时定量荧光PCR（qRT-PCR）验证关键分子。高剂量EWH干预可显著降低雌性SHRs的血压。生物信息学分析共筛选得到90个差异表达miRNA。