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首页> 外文期刊>American Journal of Physiology >Pravastatin treatment attenuates interstitial inflammation and fibrosis in a rat model of chronic cyclosporine-induced nephropathy.
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Pravastatin treatment attenuates interstitial inflammation and fibrosis in a rat model of chronic cyclosporine-induced nephropathy.

机译：普伐他汀治疗可减轻慢性环孢素诱导的肾病大鼠模型的间质炎症和纤维化。

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We investigated the effects of pravastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on interstitial inflammation and fibrosis, using an animal model of chronic cyclosporine A (CsA)-induced nephropathy. Sprague-Dawley rats were maintained on a low-salt diet (0.05% sodium) and treated daily for 1 or 4 wk with vehicle (olive oil; 1 ml/kg sc), CsA (15 mg/kg sc), or both CsA and pravastatin (5 or 20 mg/kg in the drinking water). Anti-inflammatory and antifibrotic effects of pravastatin were studied by evaluating the concentrations of the inflammatory mediators osteopontin (OPN) and C-reactive protein (CRP), of fibrotic cytokine-transforming growth factor (TGF)-beta1, and the presence of ED-1-positive cells (macrophages). In addition, renal function, serum lipid levels, histopathology (arteriolopathy and tubulointerstitial fibrosis), and the expression of the vasoactive factors endothelial nitric oxide synthase (eNOS) and renin protein were also compared for different treatment groups. Pravastatin induced dose-dependent decreases in the expression of OPN, intrarenal CRP, and TGF-beta1, and in the numbers of ED-1-positive cells at 1 and 4 wk. These were accompanied by a significant attenuation of tubulointerstitial fibrosis at 4 wk. The downregulation of eNOS protein expression in CsA-treated rat kidney was markedly upregulated by pravastatin treatment, although intrarenal renin expression was unaffected. Renal dysfunction induced by CsA significantly improved with administration of pravastatin at a dose of 20 mg/kg. Neither CsA nor pravastatin influenced serum lipid or high-sensitivity CRP levels in the treatment groups. Thus in chronic CsA nephropathy, pravastatin effectively abrogates the progression of tubulointerstitial inflammation and fibrosis. This may support the clinical use of pravastatin.
机译：我们使用慢性环孢素A（CsA）诱发的肾病动物模型研究了普伐他汀（3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶的竞争性抑制剂）对组织间炎症和纤维化的影响。将Sprague-Dawley大鼠维持在低盐饮食（0.05％钠）下，每天用溶媒（橄榄油; 1 ml / kg sc），CsA（15 mg / kg sc）或两种CsA治疗1或4 wk和普伐他汀（饮用水中5或20毫克/千克）。通过评估炎症介质骨桥蛋白（OPN）和C反应蛋白（CRP），纤维化细胞因子转化生长因子（TGF）-beta1的浓度以及ED-的存在，研究了普伐他汀的抗炎和抗纤维化作用1阳性细胞（巨噬细胞）。此外，还比较了不同治疗组的肾功能，血脂水平，组织病理学（动脉病变和肾小管间质纤维化）以及血管活性因子内皮型一氧化氮合酶（eNOS）和肾素蛋白的表达。普伐他汀诱导1和4周时OPN，肾内CRP和TGF-beta1的表达以及ED-1阳性细胞的数量呈剂量依赖性降低。这些伴随着4周时肾小管间质纤维化的明显减弱。普伐他汀治疗显着上调了经CsA处理的大鼠肾脏中eNOS蛋白表达的下调，尽管肾内肾素的表达不受影响。通过以20 mg / kg的剂量服用普伐他汀可以明显改善CsA引起的肾功能不全。 CsA和普伐他汀均未影响治疗组的血脂或高敏CRP水平。因此，在慢性CsA肾病中，普伐他汀可有效消除肾小管间质炎症和纤维化的发展。这可能支持普伐他汀的临床使用。

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