This study focused on how Astragalus polysaccharides (APS) regulate the p38 MAPK/NF-κB signaling pathway cascade during the proliferation and apoptosis phases in an endothelial injury model induced by lipopolysaccharide (LPS) (to validate sepsis). Normal human microvascular ECs (HMECs) were used as the control group. APS promotes LPS-induced endothelial cell proliferation (endothelial injury model for validating sepsis) (LPS group). Based on the LPS group, cells were treated with 25 mg/L APS (LPS + APS group) and with 25 mg/L APS + 100 μM dimethyloxalylglycine (LPS + APS + DMOG group). The cell proliferation was evaluated using the MTT assay, and apoptosis levels were examined via flow cytometry. Additionally, quantitative determinations were conducted for tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1, IL-6, tissue factor (TF), von Willebrand factor (vWF), and lactate dehydrogenase (LDH). Moreover, targeted identification and analysis were carried out for the protein molecules that are functionally correlated with the p38 MAPK/NF-κB signaling pathway. Relative to the control group, the LPS cohort exhibited suppressed cellular proliferative capacity, a heightened incidence of apoptotic events, and augmented concentrations of TNF-α, IL-1, IL-6, TF, vWF, HSP70, ESM-1, TLR4, MyD88, and Bax; on the contrary, the amounts of Cyclin D1 and Bcl-2 were diminished ( P < 0.05). In comparison with the LPS cohort, both the LPS + APS cohort and the LPS + APS + DMOG cohort displayed enhanced proliferative activity, a declined apoptotic rate, reduced concentrations of TNF-α, IL-1, IL-6, TF, vWF, HSP70, ESM-1, TLR4, MyD88, and Bax, and facilitated the expression of Cyclin D1 and Bcl-2 ( P < 0.05). In contrast to the LPS + APS cohort, the LPS + APS + DMOG cohort presented more notable alterations in the aforementioned parameters ( P < 0.05). APS attenuated the LPS-induced reduction in endothelial cell viability and protected against LPS-induced apoptosis by means of the selective suppression targeting the p38 MAPK/NF-κB signaling cascade.
Li et al. (Sat,) studied this question.