Abstract: Objective To investigate the underlying mechanisms of vitamin D treatment improves early-stage renal damage in hypertensive mice. Methods From December 2022 to December 2023, peripheral blood samples were collected from 20 hypertensive patients with early-stage renal injury and healthy controls. ELISA was used to detect interleukin-6 (IL-6), C-reactive protein (CRP) and reactive oxygen species (ROS). RT-qPCR and Western blot were utilized to measure the expression of Klotho and disulfidptosis-related proteins [glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT3) and solute carrier family 7 member 11 (SLC7A11)]. A mouse model of hypertension with early-stage renal damage was established and treated with vitamin D. Kidney tissue samples were collected for HE staining and ELISA to assess inflammatory factors, and RT-qPCR and Western blot were used to examine the expression of Klotho and disulfidptosis-related proteins. Results Compared to the control group, the level of IL-6, CRP and ROS was significantly increased in the hypertensive patients with early-stage renal damage (P＜0.05). The expression of GLUT1 and GLUT3 was significantly increased, while the expression of Klotho and SLC7A11 was significantly decreased (P＜0.05). In the mouse model of hypertension with early-stage renal damage, HE staining showed that the level of inflammatory factors in the model group was significantly higher than that in control group. Vitamin D suppressed the level of inflammatory factors, increased the expression of Klotho and SLC7A11 and inhibited the expression of GLUT1 and GLUT3 in the model group (P＜0.05). Conclusions Vitamin D treatment effectively improves inflammatory response in hypertensive mice with early renal injury.

Key words: hypertension with early renal injury, vitamin D, Klotho, disulfidptosis