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培哚普利通过抑制糖尿病大鼠清道夫受体 A 的过度表达减轻肾小管间质损伤。

Perindopril attenuates renal tubulointerstitium injury by inhibiting scavenger receptor A over-expression in diabetic rats.

机构信息

Department of Endocrinology, the Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai 51900, Guangdong Province, China.

出版信息

J Endocrinol Invest. 2012 May;35(5):511-5. doi: 10.3275/7867. Epub 2011 Jul 13.

DOI:10.3275/7867
PMID:21765240
Abstract

Scavenger receptor A (SR-A) is the main receptor through which oxidized LDL (oxLDL) and advanced glycation end products get into the cells. The aim of the present study was to investigate the effect of an ACE inhibitor, perindopril, on the expression of SR-A in renal tubulointerstitium of diabetic rats. Diabetes was induced in male Sprague-Dawley rats by injection with streptozotocin. The rats were then randomly divided into 3 groups: normal control group; untreated diabetes mellitus group; and diabetes mellitus group treated with the ACE inhibitor, perindopril. After a 24-week treatment, tubulointerstitial injury index was assessed on Masson's trichrome sections. The number of macrophages and the expression of SR-A protein in renal tubulointerstitium were detected by immunohistochemistry and the expression of SR-A mRNA was detected by RT-PCR. The tubulointerstitial injury index, the number of macrophages and the expression of SR-A mRNA were significantly higher in the diabetes group than the normal control group. Perindopril treatment not only attenuated the tubulointerstitial injury and the macrophages infiltration but also reduced the overexpression of SR-A mRNA in diabetic rats. The expression of SR-A protein was most obvious in renal tubulointerstitium in diabetic rats, which was attenuated by perindopril treatment. The findings of the present study indicate that perindopril may have renoprotective effects of diabetic nephropathy via inhibiting the expression of SR-A in renal tubulointerstitium.

摘要

清道夫受体 A(SR-A)是氧化型 LDL(oxLDL)和晚期糖基化终产物进入细胞的主要受体。本研究旨在探讨血管紧张素转换酶抑制剂培哚普利对糖尿病大鼠肾小管间质中 SR-A 表达的影响。雄性 Sprague-Dawley 大鼠经链脲佐菌素注射诱导糖尿病。然后将大鼠随机分为 3 组:正常对照组;未治疗的糖尿病组;和糖尿病组用 ACE 抑制剂培哚普利治疗。24 周治疗后,用 Masson 三色法评估肾小管间质损伤指数。通过免疫组织化学检测肾间质中巨噬细胞数量和 SR-A 蛋白的表达,通过 RT-PCR 检测 SR-A mRNA 的表达。糖尿病组的肾小管间质损伤指数、巨噬细胞数量和 SR-A mRNA 的表达均明显高于正常对照组。培哚普利治疗不仅减轻了肾小管间质损伤和巨噬细胞浸润,还降低了糖尿病大鼠中 SR-A mRNA 的过度表达。糖尿病大鼠肾间质中 SR-A 蛋白的表达最为明显,培哚普利治疗后减弱。本研究结果表明,培哚普利可能通过抑制肾小管间质中 SR-A 的表达对糖尿病肾病具有肾脏保护作用。

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本文引用的文献

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Perindopril attenuates tubular hypoxia and inflammation in an experimental model of diabetic nephropathy in transgenic Ren-2 rats.培哚普利可减轻转基因Ren-2大鼠糖尿病肾病实验模型中的肾小管缺氧和炎症。
Nephrology (Carlton). 2008 Dec;13(8):721-9. doi: 10.1111/j.1440-1797.2008.01008.x. Epub 2008 Sep 25.
2
Atherogenic scavenger receptor modulation in the tubulointerstitium in response to chronic renal injury.慢性肾损伤时肾小管间质中致动脉粥样硬化的清道夫受体调节
Am J Physiol Renal Physiol. 2007 Aug;293(2):F575-85. doi: 10.1152/ajprenal.00063.2007. Epub 2007 May 30.
3
Diabetic nephropathy: where hemodynamics meets metabolism.
糖尿病肾病:血流动力学与代谢的交汇之处
Exp Clin Endocrinol Diabetes. 2007 Feb;115(2):69-84. doi: 10.1055/s-2007-949721.
4
Macrophage scavenger receptor-a-deficient mice are resistant against diabetic nephropathy through amelioration of microinflammation.巨噬细胞清道夫受体-a缺陷小鼠通过改善微炎症反应而对糖尿病肾病具有抗性。
Diabetes. 2007 Feb;56(2):363-72. doi: 10.2337/db06-0359.
5
Scavenger receptor class A type I/II (CD204) null mice fail to develop fibrosis following silica exposure.I/II型清道夫受体A类(CD204)基因敲除小鼠在接触二氧化硅后不会发生纤维化。
Am J Physiol Lung Cell Mol Physiol. 2005 Aug;289(2):L186-95. doi: 10.1152/ajplung.00474.2004. Epub 2005 Apr 22.
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Enalapril attenuates angiotensin II-induced atherosclerosis and vascular inflammation.依那普利可减轻血管紧张素 II 诱导的动脉粥样硬化和血管炎症。
Atherosclerosis. 2005 Jan;178(1):9-17. doi: 10.1016/j.atherosclerosis.2004.08.023.
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Expression of class A scavenger receptor is enhanced by high glucose in vitro and under diabetic conditions in vivo: one mechanism for an increased rate of atherosclerosis in diabetes.在体外高糖环境以及体内糖尿病状态下,A类清道夫受体的表达均会增强:这是糖尿病中动脉粥样硬化发生率增加的一种机制。
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