摘要
目的 证实内质网应激(ERS)和自噬的交互作用对血管钙化(VC)的影响。方法 维生素D3肌注和尼古丁灌胃制备大鼠在体血管钙化模型,取主动脉行茜素红染色和钙含量检测,Western blot检测相关蛋白的表达水平。结果 与对照组相比,钙化组大鼠主动脉管壁钙沉积显著增加,血管平滑肌细胞(VSMC)收缩表型标志蛋白SM-22α和Calponin表达显著降低,而成骨细胞样表型标志蛋白骨形态发生蛋白2(BMP-2)和Runt相关转录因子2(RUNX2)表达显著升高,ERS标志蛋白葡萄糖调节蛋白(GRP78)和C/EBP同源蛋白(CHOP)以及自噬标志蛋白轻链3(LC3Ⅱ)和Beclin-1表达显著升高。钙化大鼠应用ERS激动剂衣霉素[10 μg/(kg·d)]可进一步增加血管壁钙沉积及BMP-2和RUNX2表达水平,而SM-22α和Calponin表达进一步减少,GRP78和CHOP以及LC3Ⅱ和Beclin-1表达水平进一步增加。钙化大鼠应用自噬抑制剂3-甲基腺嘌呤[10 mg/(kg·d)]可降低LC3Ⅱ和Beclin-1水平,同时GRP78和CHOP表达升高,增加血管壁钙沉积及BMP-2和RUNX2表达水平,降低SM-22α和Calponin表达。结论 内质网应激与自噬的交互作用影响血管钙化的发展。
Aim To determine the effect of interplay between endoplasmic reticulum stress (ERS) and autophagy on vascular calcification (VC).Methods VC model in rats was induced by vitamin D3 plus nicotine.The deposition of calcium in aorta was determined by alizarin red staining and assessment of calcium content.The protein levels in aorta were measured by Western blot.Results Compared with control group, deposition of calcium in aorta was increased in VC group.The protein levels of SM-22α and calponin in calcified vessels were decreased, whereas that of bone morphogenetic protein 2 (BMP-2) and RUNX2 was increased.ERS and autophagy was activated in calcified aorta, shown by increased levels of glucose regulated protein (GRP78), C/EBP homogous protein (CHOP), LC3Ⅱ and Beclin-1.Tunicamycin (10 μg/kg per day), an ERS inducer exacerbated VC and transdifferation of vascular smooth muscle cells from contracted-like to osteoblasts-like phenotype.It also promoted ERS and auphagy.3-methyladenine (10 mg/kg per day), an autophagy inhibitor prevented stimulation of autophagy, but promoted ERS activation in calcified aorta, while it also exaggerated VC and transdifferation of vascular smooth muscle cells.Conclusion The interplay between ERS and autophagy plays an important role in progression of VC.
作者
李艳青
付佳
李彤
任阳阳
许椅鑫
辛庆杰
董建龙
杨锐
武宇明
滕旭
LI Yanqing;FU Jia;LI Tong4;REN Yangyang4;XU Yixin4;XIN Qingjie;DONG Jianlong;YANG Rui;WU Yum-ing;TENG Xu(Department of Physiology,Hebei Medical University,Shijiazhuang f Hebei 050017;Department of Gynecology,Hebei Hospital of Chinese Mediciney Shijiazhuangy Hebei 050011;Clinical Medicine Major,Hebei Medical University,Shijiazhuang,Hebei 050017;Public Health Major,Hebei Medical Universityt Shijiazhuang,Hebei 050017;Hebei Key Lab of Laboratory Animal Science,Hebei Medical University,Shijiazhuang,Hebei 050017,China)
出处
《中国动脉硬化杂志》
CAS
2018年第11期1099-1105,共7页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金(81770499)
河北省自然科学基金(H2016206264)
大学生创新创业训练计划(USIP2017017,国家级)
关键词
血管钙化
平滑肌细胞表型转化
内质网应激
自噬
vascular calcification
transdifferation of vascular smooth muscle cells
endoplasmic reticulum stress
autophagy
