p38 MAPK通路激活内质网应激参与高糖诱导血管平滑肌细胞钙化  

Involvement of p38 MAPK-activated endoplasmic reticulum stress in high glucose-induced calcification of vascular smooth muscular cells

作　　者：郭润民 刘畅 吴子君 姜佳美 吴斌 李兴岳 梁国标 陈科辉 彭畅 李腾 何松坚 莫海亮 李上海 朱强[2] 游琼 吴铿 

机构地区：[1]广东医科大学附属医院心血管内科,广东湛江524001 [2]广东省人民医院内分泌科,广东广州518001

出　　处：《广东医学院学报》2016年第3期225-229,共5页Journal of Guangdong Medical College

基　　金：广东省自然科学基金项目(No.2015A030310359;2016A030313678);广东省重大科技专项(No.2012A080202020);湛江市财政资金科技专项竞争性分配项目(No.2014A01033);广东医学院附属医院博士启动项(No.BJ201511);湛江目市财政资金专项备用金项目(No.2015C01006);广东省医学科学技术研究基金(No.A2016143)

摘　　要：目的探讨p38 MAPK通路是否通过激活内质网应激及凋亡参与高糖所致血管平滑肌细胞(vascular smooth muscular cell,VSMCs)钙化。方法大鼠VSMCs分为对照组、高糖组(35μmol/L D-葡萄糖)、内质网应激抑制剂4-苯基丁酸(4-PBA)组、p38 MAPK通路抑制剂SB203580组、β-磷酸甘油组、4-PBA+高糖组、SB203580+高糖组、β-磷酸甘油+高糖组,分别用比色法、o-cresolphthalein法和Western blot测定碱性磷酸酶(ALP)活性、钙含量和骨分化转录因子(Runx2和Osterix)表达。结果 D-葡萄糖处理3、7d上调VSMCs ALP活性、钙含量和骨分化标志蛋白表达;SB203580下调ALP活性、钙含量和骨分化转录因子表达,而4-PBA抑制高糖引起VSMCs内质网应激及凋亡。结论 p38 MAPK通路通过激活内质网应激和凋亡可能是高糖诱导VSMCs钙化的重要机制。Objective To investigate whether p38 MAPK pathway is implicated in high glucose（HG）-induced calcification of vascular smooth muscular cells （VSMCs） via endoplasmic reticulum stress （ERS） and apoptosis. Methods Rat-derived VSMCs were divided into control, HG （35 μmol/L D-glucose）, ERS inhibitor 4-phenylbutyric acid （4-PBA）, p38 MAPK pathway inhibitor SB203580, β-glycerol phosphate （BGP）, 4-PBA＋ HG, SB203580＋HG, and BGP＋ HG groups. Alkaline phosphatase （ALP） activity, calcium content, and expression of bone differentiation transcription factors （Runx2 and Osterix） were measured using colorimetry, o-cresolphthalein and Western blot, respectively. Results ALP activity, calcium content and expression of bone differentiation transcription factors in VSMCs were elevated after treatment with D-glucose for 3 or 7 days, while these changes were down-regulated by SB203580. Furthermore, 4-PBA inhibited HG-induced ERS and apoptosis of VSMCs. Conclusion The p38 MAPK pathway-activated ERS and subsequent apoptosis may be the main mechanism on HG- elicited calcification of VSMCs.

关 键 词：高糖 P38 MAPK 内质网应激 血管平滑肌细胞 钙化 

分 类 号：R363[医药卫生—病理学]