糖基化终末产物所致大鼠肾皮质损伤与Na^+/H^+交换蛋白1关系的探讨  

Na^+/H^+ exchanger 1 and renal cortical injury induced by advanced glycation end products

作　　者：陈庚容[1] 杨旭红[1] 周寿红[1] 宋涛[1] 吴树金[1] 刘立英[1] 

机构地区：[1]中南大学药学院,长沙410078

出　　处：《中南药学》2009年第2期81-84,共4页Central South Pharmacy

基　　金：国家自然科学基金项目(No.30600248)

摘　　要：目的观察Na+/H+交换蛋白1(NHE-1)抑制剂cariporide对糖基化终末产物(AGEs)所致肾皮质损伤的影响,探讨NHE-1在AGEs所致肾损伤中的作用。方法参考文献方法制备肾皮质薄片,用外源性AGEs与肾薄片在DMEM培养液(37℃,95%O2和5%CO2)孵育120 min,以乳酸脱氢酶(LDH)漏出率、丙二醛(MDA)含量,谷胱甘肽(GSH)活性和NHE-1表达为指标,观察NHE-1抑制剂cariporide、anti-RAGEs对AGEs所致肾皮质损伤的影响。结果AGEs能明显上调肾皮质NHE-1表达,使肾皮质中MDA含量和孵育液中LDH漏出率分别升高2.2倍和2.4倍(P<0.01),GSH活性降低3.5倍(P<0.01);Cariporide(0.1、1μmol.L-1)能显著抑制AGEs引起的这些变化(P<0.01)。anti-RAGE也能明显阻断AGEs对肾皮质的损伤作用(P<0.01)。结论AGEs引起的肾皮质损伤主要是通过与受体RAGE结合所导致,NHE-1激活可能参与了AGE-RAGE反应引起肾损伤。Objective To observe the effect of cariporide on the renal cortical injury induced by advanced glycation end products （AGEs）, and explore the role of Na＋/H＋ exchanger 1 （NHE-1） in AGEs-mediating renal cortex damage. Methods Kidney slices were produced in vitro as in previous study and then placed in incubation tanks filled with 5 mL DMEM medium （95 %O2 5 % CO2 ）, 7 to 8 slices in each tank. The slices were respectively incubated with ectogenic AGEs and cariporide, NAC or anti-RAGE for 120 rain. The MDA concentration, GSH activities, LDH leakage and NHE-1 expression in the renal cortex were detected. Results AGEs significantly increased MDA production and LDH leakage rate by 2. 2 folds and 2.4 folds （P〈0. 05） respectively and decreased GSH activity by 3. 5 folds （P〈0. 05）. AGEs also increased NHE-1 expression in the renal cortex （ P 〈 0.05 ）. Cariporide could evidently suppress these changes induced by AGEs in a dose-dependent manner （P〈0. 05）. Anti-RAGE could also attenuate the cortex damage induced by AGEs. Conclusions AGEs mediating renal cortex damage is mainly through combining the receptor RAGE. NHE-1 activation plays an important role in the pathogenesis of renal cortex damage induced by AGEs.

关 键 词：肾皮质薄片 糖基化终末产物 Na+/H+交换蛋白1 CARIPORIDE anti-RAGEs 

分 类 号：R965.2[医药卫生—药理学]