CAJ | 학술논문

目的观察阿托伐他汀对大鼠甲状旁腺素1-34(rPTH 1-34)致心肌细胞肥大的保护作用,探讨阿托伐他汀抗心肌肥厚与小鸟苷酸三磷酸结合蛋白(Ras)细胞外信号调节激酶1/2(ERK1/2)的关系.方法体外培养新生Wistar大鼠的心室肌细胞,rPTH1-34诱导建立心肌细胞肥大模型,加入阿托伐他汀、甲羟戊酸进行干预,软件测定细胞直径,3H-亮氨酸掺入率检测心肌细胞蛋白合成速率,BCA法测定单个细胞蛋白含量,ELISA法检测心房利钠肽(ANP)、B型利钠肽(BNP)浓度的变化,Western blot方法测定Ras K亚基(K-Ras)、ERK1/2、磷酸化(p)-ERK1/2蛋白的表达变化.结果阿托伐他汀能减少心肌细胞直径、细胞蛋白合成速率和单个细胞蛋白含量,降低ANP及BNP浓度,同时抑制K-Ras及p-ERK1/2蛋白的表达(P＜0.05).使用甲羟戊酸后能部分拮抗阿托伐他汀的作用,使心肌细胞直径、细胞蛋白合成速率和单个细胞蛋白含量增加,ANP和BNP浓度升高(P＜0.05)；同时使K-Ras及p-ERK1/2蛋白的表达增加(P＜0.05).结论阿托伐他汀具有抑制PTH1-34介导的体外心室肌细胞肥大的作用,Ras-ERK1/2途径可能参与了该过程.
목적 관찰아탁벌타정대대서갑상방선소1-34(rPTH 1-34)치심기세포비대적보호작용,탐토아탁벌타정항심기비후여소조감산삼린산결합단백(Ras)세포외신호조절격매1/2(ERK1/2)적관계.방법 체외배양신생Wistar대서적심실기세포,rPTH1-34유도건립심기세포비대모형,가입아탁벌타정、갑간무산진행간예,연건측정세포직경,3H-량안산참입솔검측심기세포단백합성속솔,BCA법측정단개세포단백함량,ELISA법검측심방리납태(ANP)、B형리납태(BNP)농도적변화,Western blot방법측정Ras K아기(K-Ras)、ERK1/2、린산화(p)-ERK1/2단백적표체변화.결과 아탁벌타정능감소심기세포직경、세포단백합성속솔화단개세포단백함량,강저ANP급BNP농도,동시억제K-Ras급p-ERK1/2단백적표체(P＜0.05).사용갑간무산후능부분길항아탁벌타정적작용,사심기세포직경、세포단백합성속솔화단개세포단백함량증가,ANP화BNP농도승고(P＜0.05)；동시사K-Ras급p-ERK1/2단백적표체증가(P＜0.05).결론 아탁벌타정구유억제PTH1-34개도적체외심실기세포비대적작용,Ras-ERK1/2도경가능삼여료해과정.
Objective To investigate the effects of atorvastatin on parathyroid hormone1-34 (PTH1-34) induced neonatal rat cardiomyocytes hypertrophy and on the expression changes of small GTP-binding protein (K-Ras) and extracellular signal regulated protein kinases 1/2 (ERK1/2).Methods Neonatal rat cardiomyocytes hypertrophy was established with 10-7 mol/L rPTH1-34 in the presence or absence of 10-5 mol/L atorvastatin or 10-4 mol/L mevalonic acid (MVA).Cardiomyocyte diameter was measured by Motic Images Advanced 3.0 software,the synthetic rate of protein in cardiomyocytes was determined by 3 H-leucine incorporation and single-cell protein content was measured by BCA.The concentration of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined by ELISA.Protein expression of ERK1/2、p-ERK1/2 and K-Ras was detected by Western blot.Results Compared to PTH1-34 group,cellular diameter was decreased 12.07 μm,3 H-leucine incorporation decreased 1622 cpm/well and singlecell protein content decreased 84.34 pg,ANP or BNP concentration reduced 7.13 μg/L or 20.04 μg/L,protein expression of K-Ras,ERK1/2 or p-ERK1/2 downregulated 0.81,0.19 and 1.44 fold,respectively,in PTH1-34 plus atrovastatin co-treated cardiomyocytes (all P ＜ 0.05).Compared to PTH1-34 plus atrovastatin co-treated group,cardiomyocyte diameter increased 4.95 μm,3H-leucine incorporation increased 750 cpm/well and single-cell protein content increased 49.08 pg,ANP or BNP increased 3.12μg/L or 9.35 μg/L aud protein expression of K-Ras,ERK1/2 or p-ERK1/2 upregulated 0.52,0.06 and 1.19 fold (all P ＜ 0.05) in MVA,PTH1-34 and atrovastatin co-treated cardiomyocytes.Conclusions Atrovastatin attenuates PTH1-34 induced neonatal rat cardiomyocytes hypertrophy through downregulating K-Ras and ERK1/2 pathway.