Effects of three types of fresh Rehmannia glutinosa improve lipopolysaccharide-induced acute kidney injury in sepsis through the estrogen receptor pathway

Objective(s): To explore the effects and mechanism of three types of fresh Rehmannia glutinosa, namely Beijing No. ۳ (BJ۳H), Huaizhong No. ۱ (HZ۱H), and Taisheng (TS) on lipopolysaccharide (LPS)-induced acute kidney injury in the sepsis (S-AKI) mice model through the estrogen receptor pathway.Materials and Methods: BALB/c mice were randomly divided into control (CON), model (LPS), astragalus injection (ASI), BJ۳H, HZ۱H, TS water extract groups, the estrogen receptor antagonist ICI۱۸۲,۷۸۰ groups were added to each group. The antagonist groups received an intraperitoneal injection of ICI ۰.۵ hr before administration and an intraperitoneal injection of LPS ۳ days after administration. The kidney pathology, function, inflammatory factors, immune cells, levels of reactive oxygen species (ROS), apoptosis, and the protein expression levels of TLR۴/NF-κB/NLRP۳ signaling pathway in the mice kidneys were detected.Results: ASI, BJ۳H, HZ۱H, and TS improved LPS-induced renal pathology in S-AKI mice, reduced the kidney and serum levels of inflammatory factors, positive rates of macrophages and neutrophils, levels of ROS and apoptosis, and the relative expression levels of TLR۴, MyD۸۸, NF-κB p-p۶۵/NF-κB p۶۵, and NLRP۳ proteins in the kidney. In addition, they increased the positive rate of dendritic cells (DCs) in the mice kidneys. The overall effect of HZ۱H was superior to that of ASI, BJ۳H, and TS. However, after adding ICI, the regulatory effects of drugs were inhibited.Conclusion: The three types of fresh R. glutinosa may completely or partially affect the TLR۴/NF-κB/NLRP۳ signaling pathway through the estrogen receptor pathway to exert a protective effect on S-AKI.

کلیدواژه ها:

Acute kidney injury ، Estrogen ، Fresh Rehmannia glutinosa ، Lipopolysaccharide ، NF-kappa B ، NLRP۳ ، Sepsis ، TLR۴