慢性间歇性低压低氧抑制内质网应激改善大鼠血管钙化  

Chronic Intermittent Hypobaric Hypoia Ameliorates Vascular Calcification via Inhibiting Endoplasmic Reticulum Stress in Rats

作　　者：李艳青[1] 杨锐[2] 金胜[2] 袁芳[2] 武宇明[2] 张翼[2] 滕旭[2,3] 

机构地区：[1]河北省中医院妇科,河北省石家庄市050011 [2]河北医科大学生理教研室,河北省石家庄市050017 [3]河北省实验动物重点实验室,河北省石家庄市050017

出　　处：《中国动脉硬化杂志》2015年第5期443-447,共5页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(81100229);河北省自然科学基金(C2012206063)

摘　　要：目的证实慢性间歇性低压低氧(CIHH)通过抑制内质网应激(ERS)改善大鼠血管钙化。方法使用维生素D3肌注和尼古丁灌胃(VDN)制备的大鼠在体血管钙化模型,检测主动脉组织Ca2+含量和碱性磷酸酶(ALP)活性以及血浆ALP活性,Western blot检测相关蛋白的表达水平。结果与对照组大鼠相比,VDN大鼠主动脉组织Ca2+含量和ALP活性以及血浆ALP活性均显著升高(P<0.05),同时主动脉组织平滑肌细胞收缩表型标志蛋白calponin和SM22α的表达水平显著下调(P<0.05),成骨样细胞表型标志蛋白骨形态发生蛋白2(BMP2)和RUNX2的表达水平显著上调(P<0.05)。而CIHH能够显著改善VDN大鼠的上述改变。此外,VDN大鼠主动脉组织ERS标志蛋白葡萄糖调节蛋白78(GRP78)、CHOP(C/EBP homologous protein)和active-caspase12的表达水平较对照组大鼠显著升高(P<0.05),而CIHH能够显著抑制上述蛋白表达水平的升高(P<0.05)。结论 CIHH可能通过抑制ERS,发挥改善血管钙化和平滑肌细胞表型转化的作用。Aim To determine that chronic intermittent hypobaric hypoxia( CIHH) could improve vascular calcification( VC) through blocked endoplasmic reticulum stress( ERS). Methods He rats model of VC was induced by vitamin D3 plus nicotine( VDN). The Ca2 +content of aorta and alkaline phosphatase( ALP) activity of aorta and plasma was detected. The protein expression level was measured by Western blot. Results Compared with the control group,Ca2 +content of aorta and alkaline phosphatase( ALP) activity of aorta and plasma was significantly increased in VDN rats( P < 0. 05). In calcified vascular,the protein expression of contractile phenotype of vascular smooth muscle cell( VSMC),calponin and SM22α,was down-regulated( P < 0. 05),while that of osteoblast-like phenotype of VSMC,BMP2 and RUNX2 was up-regulated. CIHH could improve the all aboved issues( P < 0. 05). Furthermore,CIHH could prevent the induction of protein level of ERS markers,GRP78,CHOP and active-caspase12 in calcified aorta( P <0. 05). Conclusions These results suggested that CIHH could ameliorate VC through inhibiting ERS,which might provide new strategy and target for prevention and therapy of VC.

关 键 词：慢性间歇性低压低氧 血管钙化 血管平滑肌细胞 内质网应激 

分 类 号：R543[医药卫生—心血管疾病]