Echinacoside protects adenine-induced uremic rats from sciatic nerve damage by up-regulating α-Klotho

OBJECTIVES: To investigate the therapeutic effect of Echinacoside on uremia-induced sciatic nerve injury and explore the specific molecular mechanism and role of α-Klotho. METHODS: SD rats were given continuous gavage of adenine to prepare a uremia-induced sciatic nerve injury model. The model was given either Echinacoside or α-Klotho by gavage. Histopathological changes of kidney and sciatic nerve were detected by H&E staining. The changes of creatinine, urea nitrogen, and urine protein were detected by biochemical detection. The changes of IL-1β and IL-18 were detected by ELISA. Nerve activity-related indicators were detected by biochemical detection. Changes in related mRNA and protein expression were detected by qPCR and western blot. RESULTS: Creatinine, urea nitrogen, urine protein, and malondialdehyde (MDA) in the model group were significantly increased and inhibited by Echinacoside and α-Klotho treatment with Echinacoside dose-dependence. Meanwhile, the activities of ATP concentration, potassium adenosine triphosphate (Na+, K+ ATPase), succinate dehydrogenase (SDH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) showed opposite trends. CONCLUSIONS: Echinacoside can significantly relieve uremia-induced sciatic nerve injury in rats. Its specific molecular mechanism is related to the inhibition of the classical cellular pyroptosis pathway, which is likely achieved by promoting α-Klotho expression.