Integrative transcriptomics and proteomics analyses to reveal the therapeutic effect and mechanism of Buxue Yimu Pills in medical-induced incomplete abortion rats

Abstract

Ethnopharmacological relevanceMedical abortions using mifepristone and misoprostol have been approved in many countries for early pregnancy loss. Despite its high success rate, this medication regimen can result in incomplete abortion, which is responsible for endometrial damage, prolonged uterine bleeding, abdominal pain, etc. Buxue Yimu Pills (BYP) is a famous Chinese medicine prescription that is widely used in the field of gynecology and obstetrics for treating patients with postpartum complications. However, the therapeutic effect and mechanism of BYP remain to be explored. Aim of the studyThis study aimed to clarify the therapeutic effect and mechanism of action of BYP in postpartum complications using mifepristone and misoprostol-induced incomplete abortion in rats. Materials and methodsExperimental medical-induced incomplete abortion model rats were constructed using mifepristone and misoprostol, and further treated with saline or BYP by intragastric administration. Detailed information regarding the changes in mRNA and protein levels in the uterine tissues of rats regulated by BYP was illustrated by RNA sequencing (RNA-seq) analysis and quantitative proteomics analysis. The differentially expressed genes and proteins were further subjected to Gene Ontology (GO) and pathway enrichment analyses and further verified using quantitative Real-time PCR (qRT-PCR) analysis and western blot assay. ResultsBYP administration markedly alleviated the increase in serum prostaglandin F2α (PGF2α) and expression of PGF2α receptor (PGF2αR) in uterine tissues and inhibited the decrease in serum chorionic gonadotrophin (CG). Compared with the model group, 674 genes were upregulated and 344 genes were downregulated by BYP administration; 108 proteins were upregulated and 48 proteins were downregulated by BYP administration. qRT-PCR analysis of the uterine tissues showed that BYP treatment reversed the variation tendency of genes, including Mmp7, Mmp14, Timp2, Col6a4, Jak2, Wnt7a, and Mylk compared with the model group. Western blot analysis showed that BYP administration affected PKCδ, Collagen VI, MMP7, TIMP2, MLCK, and p-MLC protein levels. ConclusionBYP administration facilitated uterine recovery in medical-induced incomplete abortion rats, and this therapeutic effect involved various targets and biological processes, including the TIMP2/MMP7 and MLCK/p-MLC signaling pathways, etc.