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姜黄素通过抑制大鼠核因子κB和诱导型一氧化氮合酶活性预防冲击波碎石术诱导的肾损伤。

Curcumin prevents shock-wave lithotripsy-induced renal injury through inhibition of nuclear factor kappa-B and inducible nitric oxide synthase activity in rats.

作者信息

Bas Muzaffer, Tugcu Volkan, Kemahli Eray, Ozbek Emin, Uhri Mehmet, Altug Tuncay, Tasci Ali I

机构信息

Department of Urology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, Istanbul, Turkey.

出版信息

Urol Res. 2009 Jun;37(3):159-64. doi: 10.1007/s00240-009-0186-4. Epub 2009 Apr 2.

DOI:10.1007/s00240-009-0186-4
PMID:19340419
Abstract

Shock wave lithotripsy (SWL) is commonly used for treatment of renal stones. Free oxygen radicals are involved in the pathophysiology of renal injury due to SWL. We investigated the protective effects of curcumin, which is an antioxidant and nuclear factor kappa-B (NF-kappaB) inhibitor, against renal injury. Forty-eight rats were included and divided into four groups: group 1, control; group 2, SWL (15 kW-1,500 shocks); group 3, SWL + curcumin (curcumin orally 75 mg/kg/day dissolved in 10% ethyl alcohol, 1 day before and 5 days after SWL); and group 4, SWL + vehicle (10% ethyl alcohol). The kidneys were removed on days 7 and 35 after SWL. A sample was fixed in formaldehyde solution. Renal tissues were examined for proximal tubular injury under light microscope. iNOS activity and active subunit of NF-kappaB, p65, were evaluated immunohistochemically using rat monoclonal antibodies interpreting results semiquantitatively. There were significant differences between SWL and control groups on days 7 and 35, considering histological changes under light microscope (P < 0.02). There was a significant decrease in necrosis and fibrosis in the curcumin group as compared to the SWL group. Expressions of iNOS and p65 on days 7 and 35 were at basal levels with immunohistochemical staining. These parameters had high levels in the SWL group (P < 0.02). No significant difference was present between the control and the curcumin groups (P > 0.02). Curcumin, decreasing expressions of iNOS and p65 and serum nitric oxide levels prevented interstitial, glomerular, tubular epithelial and endothelial cellular injuries. We suggest that curcumin, could be used, especially in high-risk patients, as a protective agent to prevent renal injury due to SWL.

摘要

冲击波碎石术(SWL)常用于治疗肾结石。游离氧自由基参与了SWL所致肾损伤的病理生理过程。我们研究了姜黄素(一种抗氧化剂和核因子κB(NF-κB)抑制剂)对肾损伤的保护作用。纳入48只大鼠并分为四组:第1组为对照组;第2组为SWL组(15 kW,1500次冲击);第3组为SWL + 姜黄素组(姜黄素以75 mg/kg/天口服,溶于10%乙醇,在SWL前1天和后5天给药);第4组为SWL + 赋形剂组(10%乙醇)。在SWL后第7天和第35天摘除肾脏。取一份样本固定于甲醛溶液中。在光学显微镜下检查肾组织近端肾小管损伤情况。使用大鼠单克隆抗体通过免疫组织化学方法评估诱导型一氧化氮合酶(iNOS)活性和NF-κB的活性亚基p65,并对结果进行半定量分析。考虑光学显微镜下的组织学变化,SWL组与对照组在第7天和第35天存在显著差异(P < 0.02)。与SWL组相比,姜黄素组的坏死和纤维化明显减少。免疫组织化学染色显示,第7天和第35天时,姜黄素组iNOS和p65的表达处于基础水平。这些参数在SWL组中水平较高(P < 0.02)。对照组与姜黄素组之间无显著差异(P > 0.02)。姜黄素通过降低iNOS和p65的表达以及血清一氧化氮水平,预防了间质、肾小球、肾小管上皮和内皮细胞损伤。我们建议,姜黄素尤其可用于高危患者,作为预防SWL所致肾损伤的保护剂。

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本文引用的文献

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Chronic treatment of curcumin improves hepatic lipid metabolism and alleviates the renal damage in adenine-induced chronic kidney disease in Sprague-Dawley rats.
姜黄素的慢性治疗可改善肝脂代谢,减轻腺嘌呤诱导的 Sprague-Dawley 大鼠慢性肾脏病的肾脏损伤。
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Kidney damage and renal functional changes are minimized by waveform control that suppresses cavitation in shock wave lithotripsy.通过抑制冲击波碎石术中的空化现象的波形控制,可将肾损伤和肾功能变化降至最低。
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Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages.姜黄素及其氢化代谢产物通过下调巨噬细胞中IkappaB激酶和NFkappaB激活来抑制一氧化氮合酶的比较研究。
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