马钱苷对糖基化终末产物致肾系膜细胞内质网应激的保护作用机制  

Protective mechanism of loganin on endoplasmic reticulum stress of mesangial cells induced by advanced glycation end products

作　　者：戴国英[1,2] 吕兴[1,2] 许惠琴[1,2] 沈红胜 陈玉萍[1,2] 

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]江苏省中药药效与安全性评价重点实验室,江苏南京210023

出　　处：《中草药》2016年第21期3848-3853,共6页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81374029;81073111);江苏高校优势学科建设工程资助项目(nzyzyxjp1006)

摘　　要：目的探讨山茱萸环烯醚萜苷特征性成分马钱苷对糖基化终末产物(AGEs)刺激肾小球系膜细胞(GMCs)内质网应激的保护作用及其机制。方法体外培养GMCs,并设对照组、模型组、马钱苷(0.1、1.0、10.0μmol/L)组,氨基胍(0.1、1.0、10.0μmol/L)组作为阳性对照。加入药物预孵1 h后,用AGEs(200 mg/L)刺激,24 h后采用MTS法检测马钱苷对GMCs增殖的影响;Western blotting法检测GMCs中糖基化终末产物受体(RAGE)、内质网应激相关蛋白葡萄糖调节蛋白78(GRP78)、抑制物阻抗性酯酶(IRE1)、X盒结合蛋白1(XBP1),炎症相关因子核转录因子-κB(NF-κB)、环氧合酶-2(COX-2)及前列腺素E_2(PGE_2)的表达。结果马钱苷能够抑制AGEs导致的GMCs增殖,下调RAGE蛋白的表达,改善GMCs亚细胞器损伤,降低内质网相关蛋白GRP78、IRE1的表达,减少XBP1蛋白分化,降低炎症相关蛋白NF-κB、COX-2表达,降低细胞上清中PGE2水平。结论马钱苷可改善AGEs致GMCs的内质网应激,减轻其引起的炎症反应及细胞器损伤,其作用机制与降低RAGE蛋白表达、抑制IRE1通路有关。Objective To investigate the protective effect and the mechanism of loganin （an active component in Cornus officinalis） on the endoplasmic reticulum （ER） stress of glomerular mesangial cells （GMCs） induced by advanced glycation end products （AGEs）. Methods Human GMCs were cultured in vitro and divided into control group, model group （AGEs group）, loganin group, and amino guanidine group （set as positive control, 0.1, 1.0, and 10.0 μmol/L）. After being incubated with loganin （final concentration of 0.1, 1.0, and 10.0 μmol/L） for 1 h, GMCs were stimulated by AGEs （200 mg/L） for 24 h. Then, the cell proliferation was measured of using MTS method. PGE2 was investigated by Elisa. Receptors of advanced glycation end products （RAGE）, and ER stress-related protein like GRP78, IRE1, XBP1, and inflammatory factor NF-r,B and COX-2 in GMCs were detected by Western blotting. Results Loganin could suppress the proliferation of GMCs induced by AGEs, improve the subcellular injury of GMCs, down-regulate the expression of ER stress-related protein GRP78, IRE 1, XBP 1, and RAGE, reduce the inflammation-related protein NF-κB, COX-2, and the level of PGE2. Conclusion Loganin could improve the ER stress of GMCs induced by AGEs, lessen the inflammation and subcellular injury of GMCs, its mechanism might be related to the decreased expression of RAGE and the inhibition of the IRE1 pathway.

关 键 词：马钱苷 糖基化终末产物 肾小球系膜细胞 内质网应激 前列腺素E2 

分 类 号：R285.5[医药卫生—中药学]