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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）＞140mmHg（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。
Objective To study the relationship between the activation of related factors IRE1α and endoplasmic reticulum stress (ERS) in hypertensive rats with hyperhomocysteinemia (HHcy) and vascular smooth muscle cells (VSMCs) Relationship between the expression of p-JNK and vascular remodeling in hypertension and effect of enalapril folic acid tablets (according to leaves) intervention. Methods Sixty adult male Sprague-Dawley rats were randomly divided into control group, model group (n = 30) and control group And according to leaf group, n = 12. The control group and model group were fed with normal diet and 25 g / L methionine diet respectively. The groups were fed with 25 g / L methionine diet and orally fed with leaves (10 mg / (kg · d)]. The tail artery SBP and serum homocysteine (Hcy) were measured at 2 weeks postoperatively, 6 weeks postoperatively and 10 weeks postoperatively. The morphological changes of the thoracic aorta were observed at 10 weeks postoperatively. Image Pro Plus 6.0 images The thickness of thoracic aorta was observed by software analysis. The expression of IRE1α and p-JNK in vascular smooth muscle cells was detected by immunohistochemistry and Western blot. Results The expression of SBP, Hcy, middle thoracic aorta, IRE1α and p-JNK in model group were higher than those in control group (P <0.05) 10 weeks after operation. Arterial SBP, serum Hcy, middle thoracic aortic thickness, expression of IRE1α and p-JNK in vascular smooth muscle cells were lower than those in model group (P <0.05). Conclusions The ERS factors IRE1α and p-JNK in vascular smooth muscle cells of hypertensive rats with HHcy are activated to promote the expression of pro-apoptotic factor p-JNK. Enalapril folate has the dual effects of lowering blood pressure and serum Hcy, ERS in vascular smooth muscle cells restored the homeostasis of endoplasmic reticulum and reversed vascular remodeling.