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高血压伴高同型半胱氨酸大鼠血管平滑肌细胞IRE1α和p-JNK表达对血管重构的影响及依叶片干预机制

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2017年第6期
页码:
625-630
栏目:
基础研究
出版日期:
2017-06-01

文章信息/Info

Title:
Influences of IRE1α and p-JNK Expression on vascular remodeling in hypertensive rats with hyperhomocystinemia and the effect of enalapril folic acid tablet intervention
作者:
王增强; 赵连友; 张志敏; 李 炜; 周岩芬; 鲁轩浩; 王继鹏
(第四军医大学唐都医院心血管内科，陕西 西安 710038)
Author(s):
WANG Zeng-qiang;  ZHAO Lian-you;  ZHANG Zhi-min;  LI Wei;  ZHOU Yan-fen;  LU Xuan-hao;  WANG Ji-peng
(Department of Cardiology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi, China)
关键词:
高血压;  高同型半胱氨酸血症;  血管重构;  内质网应激;  依那普利叶酸片; 大鼠
Keywords:
hypertension;  hyperhomocystinemia;  IRE1α;  p-JNK;  Vascular remodeling;  Endoplasmic reticulum stress;  enalapril folic acid
分类号:
R544.1
DOI:
-
文献标识码:
A
摘要:
目的 研究高血压伴高同型半胱氨酸血症（hyperhomocysteinemia,HHcy）大鼠血管平滑肌细胞(vascular smooth muscle cells,VSMCs)内质网应激（endoplasmic reticulum stress,ERS）时，激活相关因子IRE1α和p-JNK的表达与高血压血管重构的关系及依那普利叶酸片(依叶片)对其干预效果。方法 60只成年雄性SD大鼠行腹主动脉缩窄术（PAAC），术后2周选收缩压(SBP)>140 mmHg（1 mmHg=0.133 kPa）大鼠36只随机分为对照组、模型组和依叶组，n=12。对照组和模型组分别给予普通饲料和25 g/L蛋氨酸饲料喂养，依叶组用25g/L蛋氨酸饲料喂养并依叶片〔10 mg/(kg·d)〕灌胃。于术后2周、术后6周、术后10周测尾动脉SBP和血清同型半胱氨酸（homocysteine,Hcy），术后10周HE染色观察胸主动脉形态变化,Image Pro Plus 6.0图像分析软件观察胸主动脉中层厚度变化，免疫组化和Western blot检测血管平滑肌细胞IRE1α和p-JNK的表达。结果 术后10周，模型组大鼠尾动脉SBP、血清Hcy值、胸主动脉中层厚度、血管平滑肌细胞IRE1α和p-JNK表达均高于对照组（P<0.05）；依叶组大鼠尾动脉SBP、血清Hcy值、胸主动脉中层厚度、血管平滑肌细胞IRE1α和p-JNK表达均低于模型组（P<0.05）。结论 高血压伴HHcy大鼠血管平滑肌细胞ERS因子IRE1α和p-JNK被激活，以促凋亡因子p-JNK的表达占优势；依那普利叶酸片具有降低血压和血清Hcy的双重效果，减轻血管平滑肌细胞ERS，恢复内质网稳态，逆转血管重构。
Abstract:
AIM The aim of the study was to investigate the relationship between changes in inositol requiring enzyme 1α(IRE1α)and c-Jun N-terminal kinases (p-JNK) expression and reversal vascular remodeling (VR) in hypertensive rats with hyperhomocystinemia (HHcy) in vascular smooth muscle cells (VSMCs) Additionally, the effects of enalopril folic acid tablet intervention were evaluated.METHODS Sixty male SD rats underwent abdominal aortic constriction (PAAC). Two weeks after operation, 36 rats with systolic blood pressure (SBP)>140 mmHg were randomly divided into three groups: control, model, and enalapril folic acid tablet (n=12). The control group and the model group was given normal diet and 25 g/L methionine diet, respectively. The enalapril folic acid tablets group was given 25 g/L methionine diet and enalapril folic acid tablets[10 mg/(kg·d)].Caudal arterial SBP and blood serum homocysteine (Hcy) were measured at 2, 6, and 10 weeks after operation.Ten weeks after operation, morphological changes of VSMCs were observed by hematoxylin-eosin staining (HE), the thoracic aorta intima-media thickness (IMT) was measured by Image Pro Plus 6.0 image analyses and the expressions level of rat thoracic aorta IRE1α and p-JNK protein were detected by immunohistochemistry and Western blot.RESULTS Ten weeks after operation,the caudal artery SBP, blood serum Hcy, IMT, and expressions of IRE1α and p-JNK protein in model group were higher than those in control group (P<0.05) and the caudal artery SBP,blood serum Hcy, IMT, and expressions of IRE1α and p-JNK protein in enalapril folic acid tablets group were significantly lower than those in model group (P<0.05).CONCLUSION VSMCs IRE1α and p-JNK expressions in hypertensive rats with HHcy are activated and p-JNK expression is more dominant. Enalapril folic acid tablets had double the effect in reducing blood pressure and blood serum Hcy, mitigating VSMCs ERS, recovering endoplasmic reticulum steady-state and reversing vascular remodeling.

参考文献/References

[1]Irigoyen M,De Angelis K,Dos Santos F,et al.Hypertension, Blood Pressure Variability,and Target Organ Lesion[J].Curr Hypertens Rep,2016,18(4):31.
[2]Singh M,Mensah G A,Bakris G.Pathogenesis and Clinical Physiology of Hypertension[J].Cardiol Clin,2010,28(4):545-559.
[3]Briet M,Schiffrin EL.Treatment of Arterial Remodeling in Essential Hypertension[J].Curr Hypertens Rep,2013,15(1):3-9.
[4]Ganguly P,Alam SF.Role of homocysteine in the development of cardiovascular disease[J].Nutr J,2015,14(1):1-18.
[5]卢 凡,赵连友,张志敏,等.高同型半胱氨酸对高血压大鼠血管平滑肌细胞GRP78和CHOP的表达的影响与血管重构的关系[J].心脏杂志,2014,26(5):502-507.
[6]Balakumar P,Singh M.The possible role of caspase-3 in pathological and physiological cardiac hypertrophy in rats[J].Basic Clin Pharmacol Toxicol,2006,99(6):418-424.
[7]陈伟伟，高润霖，刘李生，等.《中国心血管病报告2015》概要[J].中国循环杂志,2016,31(6):521-528.
[8]胡大一，徐希平.有效控制H型高血压:预防卒中的新思路[J].中华内科杂志,2008,(12):976-977.
[9]Huo Y,Li J,Qin X,et al.Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China[J].JAMA,2015,313(13):1325-1335.
[10]孟 斌，高蔚娜，杨继军，等.高蛋氨酸饲料喂养的大鼠高同型半胱氨酸血症模型的实验研究[J].氨基酸和生物资源,2011(2):53-56.
[11]Spitler KM,Webb RC.Endoplasmic Reticulum Stress Contributes to Aortic Stiffening via Proapoptotic and Fibrotic Signaling Mechanisms[J].Hypertension,2014,63(3):e40-e45.
[12]Demasi M,Laurindo FRM.Physiological and pathological role of the ubiquitin-proteasome system in the vascular smooth muscle cell[J].Cardiovasc Res,2012,95(2):183-193.
[13]Kassan M,Galan M,Partyka M,et al.Endoplasmic reticulum stress is involved in cardiac damage and vascular endothelial dysfunction in hypertensive mice[J].Arterioscler Thromb Vasc Biol,2012,32(7):1652-1661.
[14]Chen Y,Brandizzi F.IRE1:ER stress sensor and cell fate executor[J].Trends Cell Biol,2013(11):547-555.
[15]Sano R,Reed J C.ER stress-induced cell death mechanisms[J].Biochim Biophys Acta,2013,1833(12):3460-3470.
[16]李建平，卢新政，霍 勇，等.H型高血压诊断与治疗专家共识[J].中华高血压杂志,2016,24(2): 123-127.
[17]郭 丽，赵连友，刘 静，等.高血压大鼠血管平滑肌细胞GRP78和caspase-12表达的变化及依那普利的干预作用[J].心脏杂志,2013,25(2):163-167.

备注/Memo

备注/Memo:
收稿日期：2017-03-13.
通讯作者：赵连友，教授，主要从事高血压发病机制及防治研究 Email:zhaolyfmmu@126.com
作者简介：王增强，住院医师，硕士生 Email:wzqaing1778@163.com
更新日期/Last Update: 2017-06-06