Active vitamin D protects the kidneys of insulin resistant rats by downregulating the TLR4-mediated inflammatory response pathway
10.3760/cma.j.cn311282-20240222-00071
- VernacularTitle:活性维生素D通过下调TLR4介导的炎症反应通路对胰岛素抵抗大鼠肾脏的保护作用
- Author:
Fang FANG
1
;
Yaxin LIU
;
Xin ZHANG
;
Mei ZHU
Author Information
1. 天津医科大学总医院内分泌代谢科,天津 300052
- Keywords:
Insulin resistance;
Kidney disease;
Vitamin D;
Toll-like receptor 4
- From:
Chinese Journal of Endocrinology and Metabolism
2024;40(8):690-696
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the protective effect and mechanism of active vitamin D against kidney disease induced by insulin resistance(IR) and its underlying mechanisms.Methods:Male SD rats were divided into three groups: normal control group(group C), simple high-fat group(group HF), and high-fat with active vitamin D group(group VD). Differences of serum biochemical indicators, renal tissue cell morphology, Toll-like receptor (TLR)4-(myeloid differentiation factor, MyD)88-NF-κB inflammatory response pathway expression in mRNA and protein levels were compared among different groups.Results:Rats in group HF showed significant IR, higher serum levels of cystatin C, alanine aminotransferase, aspartate aminotransferase, triglycerides, low density lipoprotein-cholesterol, and C-reactive protein compared to group C. Rats in group VD demonstrated significant improvements in these indicators compared with group HF. Compared with rats in group C, the morphology of renal glomeruli and tubules in group HF was abnormal, with a large number of inflammatory cells infiltrating the renal interstitium. The situation in group VD was significantly improved compared with group HF. The results of real-time fluorescence quantitative PCR, immunohistochemistry, and western blot showed higher TLR4, MyD88, and NF-κB levels in the renal tissues of group HF than those in group C. The levels of the above indicators in group VD were lower than those in group HF.Conclusion:The results of this study suggest that TLR4-MyD88-NF-κB inflammatory response pathway play an important role in the pathogenesis of IR nephropathy, and supplementing with active vitamin D can protect the kidneys of IR rats by downregulating the TLR4-mediated inflammatory response pathway. Future basic and clinical research should focus on IR nephropathy to provide more insights and evidence for prevention and treatment.