Sanqi Oral Solution Containing Serum Ameliorates C5b-9 Induced Podocyte Injury via the Endoplasmic Reticulum Stress/Unfolded Protein Response Dependent Pathway

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Sanqi oral solution (SQ), a traditional Chinese medicine that is mainly composed of Astragalus membranaceus and Panax notoginseng, has been widely used for alleviating idiopathic membranous nephropathy, but its underlying molecular mechanism remains unclear. This study aims to investigate the effects of SQ on C5b-9-induced podocyte injury and explore the underlying mechanisms. After receiving 7-day intragastric administration of SQ (6.3 mL/kg/day), blood was harvested from the abdominal aorta of mice to prepare SQ-containing serum. MPC-5 cells were stimulated by the C5b-9 complex to construct an in vitro model of podocyte injury. CCK-8, flow cytometry, and lactate dehydrogenase (LDH) assays were employed to evaluate the effect of SQ-containing serum on podocyte injury. Immunofluorescence staining was performed to investigate the intracellular reactive oxygen species (ROS) levels. Western blotting was conducted to detect the expression of synaptopodin and podocin and activation of the endoplasmic reticulum (ER) stress/unfolded protein response (UPR) pathway. SQ-containing serum markedly ameliorates the podocyte injury induced by C5b-9, as evidenced by the increased cell viability, upregulated expression level of synaptopodin and podocin, and reduced cell apoptosis and LDH activity in C5b-9-treated MPC-5 cells. Additionally, SQ-containing serum significantly suppresses ROS levels in injured podocytes. Mechanically, SQ-containing serum could significantly block C5b-9-induced intracellular activation of the ER stress/UPR pathway in podocytes. After introducing 4-PBA, an ER stress inhibitor, the protection of SQ-containing serum was hardly observed on C5b-9-treated MPC-5 cells. SQ-containing serum ameliorates podocyte injury by suppressing oxidative stress and intracellular activation of the ER stress/UPR pathway.

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