Abstract
Micro-inflammation plays an important role in the pathogenesis of spontaneously hypertensive rat (SHR). In the present study, we investigated the therapeutic potential of resveratrol (RSV), a polyphenol with anti-fibrosis activity in hypertensive renal damage model. In SHR renal damage model, RSV treatment blunted the increase in urine albumin excretion, urinary β2-microglobulin (β2-MG), attenuated the decrease in creatinine clearance rate (CCR). The glomerular sclerosis index (1.54±0.33 compared with 0.36±0.07) and tubulointerstitial fibrosis (1.57±0.31 compared with 0.19±0.04) were significantly higher in SHRs compared with Wistar Kyoto rats (WKYs), which were significantly lower by RSV treatment. The increases in mesangium accumulation and the expression of renal collagen type I (Col I), fibronectin (Fn), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) in SHR were also reduced by RSV treatment. Nuclear factor κB (NF-κB) expression was increased in the cytoplasm and nuclei of the SHR kidneys, which was significantly decreased by RSV treatment. Furthermore, the protein level of IκB-α significantly decreased in the kidneys of the SHR when compared with the WKYs. RSV treatment partially restored the decreased IκB-α level. In SHR kidney, increased expression of interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) were observed. These changes were attenuated by RSV treatment. No changes in blood pressure were detected between SHR group and SHR + RSV group. Taken together, the present study demonstrated that RSV treatment may significantly attenuate renal damage in the SHR model of chronic kidney disease (CKD). The renal protective effect is associated with inhibition of IL-6, ICAM-1 and MCP-1 expression via the regulation of the nuclear translocation of NF-κB, which suggesting that micro-inflammation may be a potential therapeutic target of hypertensive renal damage.
Highlights
It is well-documented that chronic kidney disease (CKD) is a life-threatening disease frequently associated with hypertension, progression to renal fibrosis and eventual renal failure [1,2,3,4]
Effects of RSV on renal fibrotic gene and protein expression levels in spontaneously hypertensive rat (SHR) (n=6). (A) collagen type I (Col I), Fn and plasminogen activator inhibitor-1 (PAI-1) expression by Western blot. (B–D) Quantification of Col I, Fn and PAI-1 expression is achieved using densitometric values normalized to β-actin levels. (E–H) The relative mRNA levels of Col I, Fn, PAI-1 and transforming growth factor-β (TGF-β) expression by real-time semi-quantitative PCR
The renoprotective effect is associated with inhibition of micro-inflammation cytokines including IL-6, intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein 1 (MCP-1) via the regulation of the nuclear translocation of Nuclear factor κB (NF-κB)
Summary
It is well-documented that chronic kidney disease (CKD) is a life-threatening disease frequently associated with hypertension, progression to renal fibrosis and eventual renal failure [1,2,3,4]. Numerous studies have been performed aiming to develop better strategies for treating the CKDs, the therapeutic outcome is still unsatisfactory owing to the incomplete understanding of pathological mechanisms [7,8] This situation raised an urgent request to better understand the pathogenic mechanisms of CKDs. Recently, an increased inflammatory response is known to be associated with the disease and has long been speculated to contribute to disease development [9,10]. For example several recent studies have shown that micro-inflammatory cytokines in patients with hypertension were significantly higher than normal, and further increase with the degree of renal dysfunction aggravate, which indicates that micro-inflammatory cytokines
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