Chitosan‐Low Molecular Weight Heparin Sodium Nanoparticles Regulate Treg/Th17 Immune Balance and Inflammation at the Maternal‐Fetal Interface to Ameliorate Pre‐Eclampsia by HB‐EGF

Abstract

Pre‐eclampsia is a major cause of maternal and fetal mortality. Low molecular weight heparin sodium (LMWH) reduced the incidence of pre‐eclampsia, may be an effective treatment of pre‐eclampsia. But the underlying mechanism of LMWH is unknown. To improve the molecular utilization rate, chitosan‐LMWH nanoparticles (CHsN) are purchased for the study. The prague of pregnancy Sprague‐Dawley rats are injected with nitroso l‐arginine methyl ester to construct a pre‐eclampsia model. Trichotrophoblast cells HTR‐8/SVneo are cultured under Hypoxia/reoxygenation injury (H/R) simulation conditions to construct the cell model. CHsN ameliorates the integrity of fetal membrane tissue. Administration of CHsN results in decreased urine protein and HB‐EGF levels, accompanied by increased numbers of pups and placenta. Treatment with CHsN increases the proportion of Treg cells and decreases the proportion of Th17 cells. After treatment with CHsN, the levels of LPS, TNF‐α, rank1, slp1, Foxo, NF‐κB, and HIF‐1α are down‐regulated, while the levels of IL‐2, Foxp3, and TGFβ1 are up‐regulated. CRM197 reverses the effect of CHsN. The CHsN improves H/R‐induced HTR‐8/SVneo cells apoptosis through HB‐EGF and affected CD4+T cell differentiation. CHsN ameliorates pre‐eclampsia by regulating Treg/Th17 immune balance and inflammation at the maternal‐fetal interface through HB‐EGF. This provides a theoretical reference for relieving pre‐eclampsia by CHsN.