高血压伴高同型半胱氨酸血症大鼠心肌ATF6和CHOP表达对左室肥厚的影响及依叶片干预效果

Influences of ATF6 and CHOP expression on left ventricular hypertrophy in hypertensive rats with hyperhomocystinemia and the effect of enalapril folic acid tablets intervention

目的研究高血压伴高同型半胱氨酸血症(HHcy)大鼠心肌内质网应激(ERS)时,激活作用转录因子6(ATF6)和C/EBP同源蛋白(CHOP)的表达与左室肥厚的关系及依叶片对其干预效果。方法60只雄性SD大鼠行腹主动脉缩窄术(AAC),术后2周选收缩压(SBP)≥140 mm Hg(1 mm Hg=0.133k Pa)大鼠45只随机等分为3组。AAC组普通饲料喂养并双蒸水灌胃;对照组2.5%蛋氨酸饲料喂养并双蒸水灌胃;治疗组2.5%蛋氨酸饲料喂养并依叶片[10 mg/(kg·d)]灌胃。定期测SBP和血同型半胱氨酸(Hcy),查心脏彩超,并用免疫组化和Western blot法观察大鼠心肌ATF6和CHOP的表达。结果术后20周,对照组大鼠SBP,血Hcy,室间隔舒张厚度(IVSD)和左室厚壁舒张厚度(LVPWD),心肌ATF6和CHOP表达均高于AAC组(P<0.05);治疗组大鼠SBP,血Hcy,IVSD和LVPWD,心肌ATF6和CHOP表达均明显低于对照组(P<0.05)。结论高血压伴HHcy大鼠心肌ATF6及CHOP表达较Hcy正常的高血压大鼠明显增高,以凋亡因子CHOP表达更占优势;依叶片有效降压,降低血Hcy,减轻心肌ERS,减缓心肌肥厚的作用。

Objective To Study the relationship between changes of activating transcription factor6 (ATF6) andC/EBP homologous protein (CHOP) expression with left ventricular hypertrophyin hypertension rats withhyperhomocystinemia(HHcy) on myocardial endoplasmic reticulum stress(ERS),and observe the effect of enalapril folic acid tabletsreversal left ventricular hypertrophy. Methods 60 male SD rats underwent abdominal aortic constriction (AAC). Twoweeks after operation,45 ratswhich systolic blood pressure(SBP)>140 mmHg were randomly divided into 3 groups.The AAC group was given normal diet and lavaged double distilled water; the control group was given 2.5% methioninediet and lavaged double distilled water; the treatment group received 2.5% methionine diet and lavaged enalaprilfolic acid tablets (10 mg/kg/d). SBP and blood homocysteine (Hcy) were measured regularly, echocardiographyexamination was conducted, and the expression level of rat myocardial ATF6 protein and CHOP protein were detected byimmunohistochemical and Western blot. Results 20 weeks after operation,the SBP, blood Hcy, inlet ventricular septaldefect(IVSD) and left ventricular posterior wall diameter(LVPWD), expression of myocardial ATF6 and CHOPin thecontrol group were higher than those in the AAC group (P<0.05); the SBP,blood Hcy, IVSD and LVPWD, myocardialATF6 and CHOP expression in the treatment group were significantly lower than those in the control group (P<0.05).Conclusion Myocardial ATF6 and CHOP expressionin hypertension rats with HHcy was significantly higher thanthat in hypertensive ratswith normal Hcy, and CHOP expression was more dominant. Enalapril folic acid tablets caneffectively reduce blood pressure and Hcy, mitigate myocardial ERS, relieve the myocardial hypertrophy.