CAJ | 학술논문

目的探讨血管紧张素Ⅱ受体拮抗剂替米沙坦对腹主动脉缩窄术后大鼠内质网应激相关的心肌细胞凋亡的影响.方法 30只雄性SD大鼠随机分为假手术组(n=10),腹主动脉缩窄组(n=10),腹主动脉缩窄+替米沙坦组(n=10).术后10周各组大鼠用导管法测量血液动力学指标并留取心肌标本测左心室质量指数,心肌细胞凋亡用TUNEL法检测,心肌内质网应激信号通路分子GRP78、CHOP用免疫印迹法和免疫组化法检测.结果 (1)腹主动脉缩窄组左心室质量指数(3.29±0.19)mg/g明显高于假手术组(2.17±0.22)ms/g(P<0.01),左心室舒张末压(9.71±0.52)mm Hg(1 mm Hg=0.133 kPa)亦明显高于假手术组(2.79±0.13)mm Hg,左心室收缩末压(105.61 ±6.66)mm Hg明显低于假手术组(135.02 ±5.95)mm Hg(P<0.01),而腹主动脉缩窄+替米沙坦组上述指标分别为(2.34 ±0.08)mg/g、(4.70±0.36)mm Hg、(127.62 ±4.99)mm Hg,明显优于腹主动脉缩窄组(P<0.01).(2)腹主动脉缩窄+替米沙坦组心肌细胞凋亡指数(13.42 ±0.74)%显著低于腹主动脉缩窄组(35.51 ±0.65)%(P<0.01).(3)腹主动脉缩窄组内质网应激信号分子GRP78、CHOP蛋白表达RGRP78/β-actin 0.436 ±0.007、RCHOP/β-actin 0.747±0.034显著高于假手术组RGRP78/β-actin 0.144±0.009、RCHOP/β0.316 ±0.007(P<0.01),而腹主动脉缩窄+替米沙坦组GRP78、CHOP(RGP78/β-actin 0.213±0.007、RCHOP/β0.451 ±0.019),明显低于腹主动脉缩窄组(P<0.01).结论内质网应激参与了腹主动脉缩窄术后大鼠心肌细胞凋亡,替米沙坦对内质网应激相关的心肌细胞凋亡有保护作用.
목적 탐토혈관긴장소Ⅱ수체길항제체미사탄대복주동맥축착술후대서내질망응격상관적심기세포조망적영향.방법 30지웅성SD대서수궤분위가수술조(n=10),복주동맥축착조(n=10),복주동맥축착+체미사탄조(n=10).술후10주각조대서용도관법측량혈액동역학지표병류취심기표본측좌심실질량지수,심기세포조망용TUNEL법검측,심기내질망응격신호통로분자GRP78、CHOP용면역인적법화면역조화법검측.결과 (1)복주동맥축착조좌심실질량지수(3.29±0.19)mg/g명현고우가수술조(2.17±0.22)ms/g(P<0.01),좌심실서장말압(9.71±0.52)mm Hg(1 mm Hg=0.133 kPa)역명현고우가수술조(2.79±0.13)mm Hg,좌심실수축말압(105.61 ±6.66)mm Hg명현저우가수술조(135.02 ±5.95)mm Hg(P<0.01),이복주동맥축착+체미사탄조상술지표분별위(2.34 ±0.08)mg/g、(4.70±0.36)mm Hg、(127.62 ±4.99)mm Hg,명현우우복주동맥축착조(P<0.01).(2)복주동맥축착+체미사탄조심기세포조망지수(13.42 ±0.74)%현저저우복주동맥축착조(35.51 ±0.65)%(P<0.01).(3)복주동맥축착조내질망응격신호분자GRP78、CHOP단백표체RGRP78/β-actin 0.436 ±0.007、RCHOP/β-actin 0.747±0.034현저고우가수술조RGRP78/β-actin 0.144±0.009、RCHOP/β0.316 ±0.007(P<0.01),이복주동맥축착+체미사탄조GRP78、CHOP(RGP78/β-actin 0.213±0.007、RCHOP/β0.451 ±0.019),명현저우복주동맥축착조(P<0.01).결론 내질망응격삼여료복주동맥축착술후대서심기세포조망,체미사탄대내질망응격상관적심기세포조망유보호작용.
Objective To investigate the effects of telmisartan on endoplasm retiedum (ER) stress signal pathways and eardiomyocyte apoptosis in abdominal aortic banded rats.Methods Male SD rats were randomly divided into sham-operated group,abdominal aortic banding group(AAB)and AAB+telmisartan (5 mg·kg-1·d-1 per gavage,beginning at l week before AAB for 8 weeks,n=10 each).Ten weeks post AAB,hemodynamie measurements were performed,whole heart and left ventricular weights were obtained. Cardiomyocyte apoptosis was measured by TUNEL method.Myocardial GRP78 and CHOP protein expresssions were detected by Western blot and immunohistochemistry.Results The ratio of left ventricular weight to body weisht,the ratio of heart weight to body weisht,left ventrieular end diastolic pressure and the apoptosis index were significantly increased while left ventfieular end systolic pressure and±dp/dtmax were significantly decreased in AAB group than those in sham-operated group (all P<0.01),these changes could be significantly attenuated by telmisartan (all P<0.01).Moreover,myocardial GRP78 and CHOP expressions were significantly upregulated in AAB group than those in sham-operated group and telmisartan could significantly downregulate the increased GRfp78,CHOP expressions (all P<0.01).Conclusions Increased ER stress might be responsible for enhanced eardiomyocyte apoptosis in AAB rats.Telmisartan effectively attenuated the cardiomyocyte apoptosis and cardiac hypertrophy in AAB rats possibly through reducing ER stress.