摘要
目的 探讨噻唑烷二酮 (TZD)类药物吡格列酮在体外对心肌肥大的影响。方法 新生大鼠的原代培养心肌细胞和非心肌细胞 ,以血管紧张素Ⅱ (AngⅡ )刺激建立体外心肌肥大模型 ,并用不同浓度的吡格列酮作用细胞。采用RT PCR法检测心肌肥大特征性基因心钠肽 (ANP)和脑钠肽(BNP)的mRNA表达 ,以MTT比色法和3 H TdR参入实验检测非心肌细胞增殖情况 ,以3 H 亮氨酸参入实验检测心肌细胞蛋白合成速率 ,并用软件分析心肌细胞表面积。结果 肥大模型出现后 ,心肌细胞表面积、ANP和BNP的mRNA表达以及蛋白合成速率增加 ;非心肌细胞增殖活跃 ,但ANP和BNP的mRNA表达没有变化。吡格列酮可以逆转这些变化 ,同时下调非心肌细胞的ANP和BNP的mRNA表达 ,并呈一定的剂量依赖性。结论 吡格列酮体外对大鼠心肌肥大有改善作用 。
AIM To investigate the effects of pioglitazone on cardiac hypertrophy in vitro. METHODS Hypertrophy in neonatal rat cardiac myocytes (MC) and cardiac nonmyocytes (NMC) was established with angiotensinⅡ (AngⅡ). mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was measured by reverse transcription polymerase chain reaction (RT PCR). MTT assay and 3H TdR uptake was used to estimate proliferation of NMC. The surface area of MC was analyzed by the aid of NIH Image J software, and the synthetic rate of protein in MC was detected by 3H leucine incorporation. RESULTS In the condition of hypertrophy, increases of surface area,mRNA expression of ANP and BNP and 3H leucine incorporation in MC and an increase of proliferation in NMC were detected, but no changes in mRNA expression of ANP and BNP in NMC. Pioglitazone inhibited the changes above and reduced mRNA expression of ANP and BNP in NMC in a dose dependent manner. CONCLUSION The results demonstrate that pioglitazone inhibits cardiac hypertrophy in vitro and it suggests that pioglitazone has a potential role in the prevention and treatment of cardiac diseases such as cardiac hypertrophy.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2004年第1期45-49,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助课题 No 3 0 2 70 5 5 1
全军"十五"计划面上课题资助项目 No 0 2M 0 12