Synergistic action of inflammation and lipid dysmetabolism on kidney damage in rats

Zhongjie Wang,Wenhan Huang,Hui Li,Lin Tang,Hang Sun,Qi Liu,Ling Zhang

doi:10.1080/0886022x.2018.1450763

Abstract

In kidney disease, inflammation and lipid dysmetabolism are often associated together, however, the effect and mechanism of inflammatory mediators and lipid dysmetabolism on kidney damage is still unclear. In this study, Wistar rats were randomized into four groups: normal diet + saline (Group N), high-fat diet (HF)+ saline (Group HF), normal diet + adriamycin (Group ADR), HF + adriamycin (Group ADR + HF). After 10 weeks of feeding, rats in each group were randomly sacrificed. We found that the protein content of urine in ADR and ADR + HF groups were significantly higher than that of group N and HF while the serum levels of total protein and albumin in the ADR and ADR + HF groups decreased correspondingly. The serum levels of triglyceride, total cholesterol and low-density lipoprotein in the HF, ADR and ADR + HF groups increased. In the treatment groups, mesangial proliferation, matrix accumulation, tubular vacuolization, inflammatory cell infiltration and fat deposition were detected. These pathological changes were the most serious in the ADR + HF group. The expression of tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) were increased in each treatment group, especially in the ADR + HF group. Our results suggested that the inflammatory factors and abnormal lipid levels can activate the inflammatory response in kidney of the Wistar rats, and lead to a series of pathological changes in renal tissue, and inflammatory factors and lipid dysmetabolism can aggravate damage in the kidney.

Highlights

Glomerulosclerosis and renal interstitial fibrosis is the common pathway for chronic kidney disease and kidney failure [1]
It was demonstrated that no significant differences in blood urine nitrogen (BUN) or serum creatinine (Scr) were seen between groups
‘lipid nephrotoxicity’ has been widely accepted and confirmed by some animal experiments [18], the level of plasma cholesterol is not consistent with the extent of glomerular sclerosis, which suggests that some factors other than lipids are related to glomerulosclerosis

Summary

Introduction

Glomerulosclerosis and renal interstitial fibrosis is the common pathway for chronic kidney disease and kidney failure [1]. Since 1982, when Moorhead et al [2] put forward the hypothesis of ‘lipid nephrotoxicity’ for the first time, a large number of studies have confirmed that chronic kidney diseases are often accompanied by various lipid abnormalities. Recent experimental and clinical evidence has confirmed that the pathological changes and pathophysiological mechanism of glomerulosclerosis are similar to those of atherosclerosis, and it has put forward the concept ‘glomerular atherosclerosis’ [5,6]. Recent studies have confirmed that atherosclerosis is an inflammatory disease and that inflammation is an accelerating factor for it; at the same time, the levels of inflammatory factors are found to be higher in many kinds of kidney diseases [7]. Adriamycin nephrosis is a representative animal model of nephrotic syndrome, pathologically characterized by extensive tubular injury, interstitial inflammation and renal fibrosis [8]

Methods

Results

Conclusion