ABSTRACT
Rutin reportedly conveys many beneficial effects, including renoprotection; however, it has not yet been demonstrated to have a renoprotective effect against obstructive nephropathy. The present study is the first to show a protective effect of rutin against obstructive renal injury induced by unilateral ureteral obstruction (UUO). A total of 24 male Wistar rats were randomly divided into four groups of six rats each, including vehicle- or rutin-treated sham operated groups, and vehicle- or rutin-treated UUO groups. Rats received daily oral gavage of rutin (100mg/kg) for 2weeks. All rats were euthanized on postoperative day 14. Histological findings showed that rutin administration significantly reduced renal interstitial injury and suppressed interstitial collagen deposits in UUO rats. Moreover, rutin decreased macrophage infiltration, proinflammatory cytokine expression and phosphorylation of nuclear factor-κB p65. Furthermore, rutin inhibited extracellular matrix accumulation by reducing expression of type I/III collagen and fibronectin. Rutin also prevented the epithelial-mesenchymal transition processes of renal tubular cells by decreasing α-smooth muscle actin expression and retaining E-cadherin expression. These effects of rutin were in parallel with the reductions in Smad3 activity and pivotal to the fibrogenic potential of TGF-ß1. Taken together, the renoprotective effects of rutin in obstructive nephropathy were likely due to anti-inflammatory effects and inhibition of TGF-ß1/Smad3 signaling.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Kidney Diseases/drug therapy , Kidney/drug effects , Macrophages/drug effects , Rutin/therapeutic use , Ureteral Obstruction/drug therapy , Animals , Cell Movement/drug effects , Cells, Cultured , Cytokines/metabolism , Epithelial-Mesenchymal Transition/drug effects , Extracellular Matrix/drug effects , Fibrosis , Inflammation Mediators/metabolism , Kidney/pathology , Macrophages/immunology , Male , Rats , Rats, Wistar , Signal Transduction/drug effects , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
PURPOSE: Ghrelin is a gastric peptide that modulates multiple biological functions, of which the stimulation of food intake is the most well-known function. Ghrelin also exerts potential anti-inflammatory and antifibrotic properties in different organs but to our knowledge whether ghrelin inhibits the progression of renal fibrosis is unknown. Thus, we investigated the effect and underlying mechanisms of ghrelin in a rat model of renal fibrosis. MATERIALS AND METHODS: Male Sprague Dawley® rats were divided into 4 groups, including vehicle or ghrelin treated sham operated groups and vehicle or ghrelin treated unilateral ureteral obstruction groups. Kidneys harvested on postoperative day 7 or 14 were evaluated for renal inflammation, fibrosis and apoptosis, and the expression of profibrotic and proinflammatory factors. RESULTS: Ghrelin inhibited renal fibrosis by attenuating collagen production, extracellular matrix deposition, and α-smooth muscle actin and fibronectin expression. Ghrelin administration decreased macrophage infiltration and several proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß and monocyte chemotactic protein-1, as well as phosphorylated nuclear factor-κB p65. Ghrelin also inhibited myofibroblast accumulation by blocking the transforming growth factor-ß1/Smad3 signaling pathway. Furthermore, ghrelin attenuated renal tubular cell apoptosis and epithelial-mesenchymal transition processes induced by unilateral ureteral obstruction injury. CONCLUSIONS: These findings indicate that ghrelin is a potent antifibrotic agent that may have therapeutic potential in patients with obstructive nephropathy.
Subject(s)
Ghrelin/therapeutic use , Kidney/pathology , Animals , Disease Models, Animal , Fibrosis/etiology , Fibrosis/prevention & control , Inflammation/etiology , Inflammation/prevention & control , Male , Rats , Rats, Sprague-Dawley , Ureteral Obstruction/complicationsABSTRACT
<p><b>OBJECTIVE</b>To observe the chronicity decompression effect of Astragalus Membranaceus(AM) and evaluate the effect on baroreflex sensitivity (BRS).</p><p><b>METHOD</b>Nineteen spontaneously hypertensive rats(SHR) were randomly divided into four groups. The AM groups were intraperitoneally administered with AM parenteral solution 0.9 mL, 1.2 mL and 1.8 mL respectively and the control group was not given AM for eight weeks. Then the change of blood pressure was observed successivly. After eight weeks, BRS were also determined. At last, the difference of blood pressure and BRS among the groups were compared.</p><p><b>RESULT</b>Blood pressure in the control group became higher and higher frome the third week to the eighth week, but the other SHR admistered with AM showed no changein blood pressure level. We also found that the BRS in AM group was higher than that in the control group(P < 0.01).</p><p><b>CONCLUSION</b>AM can promote the BRS in SHR.</p>
