关键词: 氨氯地平, 内质网应激, 葡萄糖调节蛋白94, CAAT/增强子结合蛋白同源蛋白, 心室肥厚

Abstract: Objective To study the expression of protein 94 (GRP94) and C/EBP-homologous protein (CHOP) in myocardial tissue of hypertensive rats, and investigate the effects of amlodipine on endoplasm retieulum stress（ERS） and ventricular hypertrophy in abdominal aortic banded rats. Methods 120 adult male SD rats with criteria were divided randomly into three groups：sham-operated group, abdominal aortic banding(AAB) and AAB treated with amlodipine (AAB+Aml）groups(n=40). In sham-operated rats, the abdominal aorta was isolated but not constricted, while the abdominal aorta were constricted in AAB rats. The AAB+Aml group were underwent abdominal aortic constriction and treated with amlodipine (10 mg/(kg?d)). According to the time of surgery，each group was further divided into 2, 4 and 8-week postoperative subgroups (n=6). Mean arterial pressure (MAP), the 1eft ventricular mass (LVM) and body mass (BM) were measured and (LVM/BM) was calculated. The morphology of cardiomyocytes was observed by HE staining. The protein levels of GRP94 and CHOP were analyzed by immunohistochemistry and western blot. Results 1)With time after surgery, MAP and LVM/BW of AAB group increased gradually, and they were obviously higher than the sham operation group〔MAP: 2 weeks (144 ± 10)vs(118 ± 9), 4 weeks (163 ± 8)vs(120 ± 7), 8周(177 ± 10)vs(120 ± 6) mmHg; LVW/BW: 2 weeks (2.21±0.17) vs (1.91±0.12), 4 weeks (2.45±0.16) vs (2.01±0.14), 8 weeks (2.68±0.15) vs (2.05±0.09) mm Hg；(P<0.05)〕.The cardiomyocytes in AAB group were hypertrophic compared to the sham group. The expression of GRP94 in AAB group increased significantly at 2 weeks post-operation, and reached peak level at 4 weeks after the surgery and was on the decline thereafter. The expression of CHOP and GRP94 in AAB rats were significantly higher than sham group, and reached the peak at the 8 weeks after surgery. 2)Treatment with amlodipine significantly reduced MAP and LVM/BW in AAB rats〔（MAP: 2 weeks (126±6) vs (144±10), 4 weeks (125±8) vs (163±8), 8 weeks (128±5) vs (177±10)mmHg；LVM/BW: 2 weeks (1.94±0.15) vs (2.21±0.17), 4 weeks (2.13±0.08) vs (2.45±0.16), 8 weeks (2.18±0.10) vs (2.68±0.15)mg/g; (P<0.05)〕.The myocardial hypertrophic was alleviated in AAB+Aml group. The levels of GRP94 and CHOP in AAB+Aml group were lower than those in AAB rats(all P<0.05). Conclusion Our results suggested that endoplasmic reticulum stress is involved in the ventricular remodeling caused by hypertension, and use of amlodipine can reduce ventricular hypertrophy in hypertension models possibly by inhibiting endoplasmic reticulum stress via down-regulation of GRP94 and CHOP.

Key words: Amlodipine, Endoplasmic reticulum stress, Glucose-regulated protein 94, CAAT/enhancer-binding protein homologous protein, Ventricular hypertrophy