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目的:观察辛伐他汀对心肌营养素-1(CT-1)诱导的大鼠心肌细胞肥大效应的影响,探讨Jak激酶/信号转导转录活化因子(JAK-STAT)信号通路与心肌细胞肥大的关系。方法:以培养的新生SD大鼠心肌细胞为实验模型,应用图像分析系统测定心肌细胞表面积[3H]-亮氨酸,掺入法测定心肌细胞蛋白合成速率,逆转录聚合酶链式反应(RT-PCR)检测心钠素(ANP) mRNA表达,蛋白免疫印迹法(Western blot)检测JAK-STAT的表达水平。结果:①CT-1(10ng/L)刺激后心肌细胞表面积明显增加,与对照组比较差异有统计学意义(P<0.01);心肌细胞表面积在给予辛伐他汀干预后逐渐减小,其在10-6和10-5mol/L辛伐他汀组明显小于CT-1组(P<0.01)。②CT-1刺激后心肌细胞[3H]-亮氨酸掺入率与对照组相比显著增高(P<0.01),辛伐他汀干预后,在10-6和10-5mol/L组[3H]-亮氨酸掺入率均显著低于CT-1组,差异有统计学意义(P<0.01)。③随着辛伐他汀干预浓度的增加,心肌细胞ANP mRNA表达水平逐渐降低,其中在10-6和10-5mol/L辛伐他汀组显著低于CT-1组(P<0.01)。④甲羟戊酸(MVA)能够明显地拮抗辛伐他汀对心肌细胞表面积、[3H]-亮氨酸掺入率、ANP mRNA表达水平的抑制作用,差异有统计学意义(P<0.01)。⑤CT-1作用后心肌细胞JAK-STAT的蛋白表达水平显著增强,辛伐他汀(10-6mol/L)可明显抑制CT-1诱导心肌细胞JAK-STAT蛋白表达水平(P<0.01),而MVA减弱辛伐他汀对JAK-STAT蛋白表达的抑制效应(P<0.01)。结论:辛伐他汀能够逆转CT-1诱导心肌细胞肥大效应,细胞因子信号通路JAK-STAT活化介导了这一过程并可能是其分子生物学机制。
AIM: To observe the effect of simvastatin on cardiomyocyte hypertrophy induced by cardiotrophin-1 (CT-1) in rats and to explore the relationship between Jak kinase / signal transducer and activator of transcription (JAK-STAT) signaling pathway and cardiomyocyte hypertrophy . Methods: Cardiac myocytes of neonatal SD rats were used as experimental models. The myocardial cell surface area [3H] -leucine was measured by image analysis system. The protein synthesis rate of cardiomyocytes, -PCR) was used to detect the expression of ANP mRNA. The protein expression of JAK-STAT was detected by Western blot. Results: (1) After treated with CT-1 (10ng / L), the cell surface area of myocardial cells increased significantly compared with that of the control group (P <0.01); the area of cardiomyocytes decreased gradually after intervention with simvastatin, -6 and 10-5mol / L simvastatin group was significantly smaller than the CT-1 group (P <0.01). Compared with the control group, the incorporation of [3H] -leucine in cardiac myocytes was significantly increased after CT-1 stimulation (P <0.01). After intervention with simvastatin, [3H] - leucine incorporation rate were significantly lower than CT-1 group, the difference was statistically significant (P <0.01). (3) With the increase of simvastatin concentration, the expression of ANP mRNA in cardiomyocytes gradually decreased, which was significantly lower in simvastatin group 10-6 and 10-5mol / L than in CT-1 group (P <0.01). Mevalonic acid (MVA) could significantly inhibit the inhibitory effect of simvastatin on myocardial cell surface area, [3H] -leucine incorporation and ANP mRNA expression, with statistical significance (P <0.01). The protein expression of JAK-STAT in cardiomyocytes was significantly increased after CT-1 treatment. Simvastatin (10-6mol / L) significantly inhibited the expression of JAK-STAT protein in cardiomyocytes induced by CT-1 (P <0.01) Attenuated the inhibitory effect of simvastatin on JAK-STAT protein expression (P <0.01). Conclusion: Simvastatin can reverse the hypertrophy induced by CT-1 and the activation of cytokines JAK-STAT mediated this process and may be the molecular biological mechanism.