Objective To study the expression of protein 94 (GRP94) and C/EBP-homologous protein (CHOP) in myocardial tissue of hypertensive rats and to investigate the effects of amlodipine on endoplasm retieulum stress ( ERS) and ventricular hypertrophy in abdominal aortic banded rats .Methods One hundred and twenty 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 isola-ted but not constricted , while the abdominal aorta were constricted in AAB rats .The AAB+Aml group was treated by 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 level of GRP 94 and CHOP was ana-lyzedbyimmunohistochemistryandwesternblot.Results 1)Withtimeaftersurgery,MAPandLVM/BWof 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 weeks(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 ) mmHg;( P<0.05 ) ] .The cardiomyocytes in AAB group were hypertrophic as 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 surger-y.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 level of GRP94 and CHOP in AAB+Aml group was lower than those in AAB rats ( all P<0.05 ) .Conclusions Endoplasmic reticulum stress is involved in the ventricular remodeling caused by hypertension , and use of amlodipine can reduce ventricu-lar hypertrophy in hypertension models possibly by inhibiting endoplasmic reticulum stress via down -regulation of GRP94 and CHOP .%目的 观察高血压大鼠心肌组织葡萄糖调节蛋白94(GRP94)和CAAT/增强子结合蛋白同源蛋白(CHOP)的表达,探讨氨氯地平与内质网应激高血压大鼠心室肥厚的关系.方法 将SD大鼠随机分为假手术组、腹主动脉缩窄术(AAB)组和氨氯地平干预(AAB+Aml)组,每组40只.给予氨氯地平10 mg/(kg·d).随机分为2、4和8周3个亚组,测定平均动脉压(MAP);计算左心室质量/体质量(LVM/BW);HE染色观察心肌细胞的形态;免疫组化及Western blot检测心肌组织GRP94和CHOP的表达.结果 随着术后时间的延长,AAB组MAP逐渐升高,明显高于假手术组[2周(144±10)比(118±9)、4周(163±8)比(120±7)、8周(177±10)比(120±6)mmHg](P<0.05);AAB组LVM/BW显著高于假手术组[2周(2.21±0.17)比(1.91±0.12)、4周(2.45±0.16)比(2.01±0.14)、8周(2.68±0.15)比(2.05±0.09)mg/g](P<0.05);AAB组心肌细胞较假手术组明显肥大;术后2周AAB组心肌组织GRP94明显表达,4周达最高值,8周减低;AAB组GRP94表达量高于假手术组(P<0.05);随术后时间的延长,CHOP蛋白含量逐渐增加,8周达最高值.使用氨氯地平后,AAB+Aml组较AAB组MAP降低[2周(126±6)比(144±10)、4周(125±8)比(163±8)、8周(128±5)比(177±10)mmHg](P<0.05);使用氨氯地平后,AAB+Aml组较AAB组LVM/BW降低[2周(2.21±0.17)比(1.94±0.15)、4周(2.45±0.16)比(2.13±0.08)、8周(2.68±0.15)比(2.18±0.10)mg/g](P<0.05);使用氨氯地平后AAB+Aml组较AAB组心肌细胞肥大程度减低.AAB+Aml组心肌组织GRP94及CHOP表达量低于AAB组(P<0.05).结论 氨氯地平可能通过减弱高血压触发的内质网应激而保护心肌细胞及减弱心室肥厚.
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