吡格列酮对压力负荷引起大鼠心肌肥厚的抑制作用  

Pioglitazone Inhibit Cardiac Hypertrophy Induced by Pressure Overload in Rats

作　　者：张铖[1] 叶平[1] 陈国林[2] 

机构地区：[1]中国人民解放军总医院老年心内科,北京100853 [2]国防大学第一门诊部,北京100091

出　　处：《中国动脉硬化杂志》2004年第3期313-316,共4页Chinese Journal of Arteriosclerosis

摘　　要：利用在体动物实验方法观察吡格列酮对大鼠心肌肥厚和心肌炎性细胞因子表达的影响,探讨该药影响心肌肥厚可能涉及的作用机制。通过不完全结扎大鼠腹主动脉引起压力负荷增加,造成左心室心肌肥厚的模型。从术前1周起用灌胃器经口给予吡格列酮[20 mg/(kg·d)]直至术后4周。处死动物,取心脏称重后计算心脏重/体重比值,将部分心脏组织制成石蜡切片,测量左心室壁厚度和心肌细胞的平均直径,其余心脏组织用于检测心肌细胞中脑钠尿肽、白细胞介素4、白细胞介素1β和心调理素1的mRNA表达。结果发现,心肌肥厚大鼠的心肌中炎性细胞因子白细胞介素1β、心调理素1和心肌肥厚标志基因脑钠尿肽mRNA表达显著增加,应用吡格列酮能够明显减少心肌肥厚大鼠上述分子mRNA表达;与心肌肥厚对照组相比,心肌肥厚用药组大鼠的心脏重、体重比值(4.77±0.25 mg/g比4.23±0.22 mg/g,p<0.05)、心肌细胞平均直径(11.6±1.3μm比10.1±1.1 μm,P<0.05)和左心室壁厚度均明显降低。此结果提示,吡格列酮可能通过抑制炎性细胞因子的表达来抑制压力负荷增加引起的心肌肥厚。Aim To investigate the antihypertrophic effects of pioglitazone and its effects on proinflammatory cytokines. Methods Cardiac hypertrophy was produced by abdominal aortic banding(AB) . Pioglitazone(20mg/kg-1 day-1 )was given orally 1 week before operation and continued till 4 weeks after operation, then the rats were killed, part of the heart was used for measurements of left ventricular wall thickness, and the mvocyte diameter, the other part of the heart was used for testing the mRNA expression of proinflammatory cytokines. Result The mRNA expression of proinflammation cytokines Interleukin-1β, Car diotropin-1 and brain natriuretic peptide (a molecular marker for cardiac hypertrophy) was markedly enhanced in the hypertrophic myocardium of AB rats. Compared with control group, treatment of AB rats with pioglitazone significantly inhibited the mRNA expression of the gene mentioned above,and reduced the increases in the heart weight-to-body weight ratio (4.77 ± 0.25 mg/g vs 4. 23 ± 0.22 mg/g, P< 0.05), myocyte diameter (11.61 ± 1.34 μm vs 10.07± 1.07 μm, P<0.05) and left ventricular wall tliickness. Conclusion Pioglitazone may attenuate cardiac hypertrophy through inhibition of proinflammatory cytokines.

关 键 词：病理学与病理生理学 吡格列酮 过氧化体增殖物激活型受体 心肌肥厚 炎性细胞因子 脑钠尿肽 压力负荷 

分 类 号：R363[医药卫生—病理学]