Hydrogen sulfide alleviates endothelial glycocalyx damage and promotes placental angiogenesis in rats exposed to cigarette smoke.

Abstract

Our previous study has shown that hydrogen sulfide (H₂S) can attenuate cigarette smoke exposure (CSE)-induced placental injury in rats. This study investigated whether H₂S alleviates CSE-induced endothelial glycocalyx (eGC) impairment and promotes placental angiogenesis in rats. Twenty-four pregnant rats were randomly divided into four groups: control, NaHS (a donor of H₂S), CSE, and CSE + NaHS. On gestational day 21, rat placentas were collected to detect H₂S levels and protein expression of the H₂S-synthesizing enzymes, cystathionine beta synthase (CBS), cystathionine gamma-lyase (CGL), and 3-mercaptopyruvate sulfurtransferase (3-MST), using a C-7Az fluorescent probe, H₂S testing kit, and western blotting, respectively. Transmission electron microscopy and double immunofluorescence staining were performed to observe the placental eGC alterations. Placental angiogenesis, vascular endothelial proliferation and apoptosis, and protein expression levels of the PI3K/AKT/mTOR signaling pathway were assessed in rat placentas. The results showed that the administration of NaHS markedly attenuated the reduction in H₂S levels and the decrease in CBS, CGL, and 3-MST expression caused by CSE in rat placentas. Notably, NaHS treatment distinctly alleviated eGC damage and facilitated placental angiogenesis in CSE-treated rats. NaHS administration effectively promoted placental vascular endothelial proliferation and suppressed endothelial apoptosis in CSE-treated rats. Furthermore, NaHS treatment markedly elevated the phosphorylation of PI3K, AKT, and mTOR in the placenta of CSE-treated rats. Taken together, these results indicate that exogenous administration of H₂S can alleviate CSE-induced eGC damage and promote placental angiogenesis in CSE-treated rats, suggesting that H₂S may be a novel therapeutic agent for the treatment of CSE-associated vascular disease.