摘要
目的探讨过氧化物酶体增殖物活化型受体(PPAR)β/δ的特异性激动剂GW0742体外抑制心肌肥厚作用的可能机制。方法取体外用血管紧张素Ⅱ(AngⅡ)诱导新生大鼠的心室肌细胞,建立心肌细胞肥厚模型,以GW0742作用于肥大的心肌细胞,设立正常组、AngⅡ组、AngⅡ+GW0742组,并测量心肌细胞表面积、3H-亮氨酸掺入法检测心肌细胞蛋白合成速率及使用RT-PCR半定量测定心钠素、脑钠素及炎性因子的表达变化。结果与正常组心肌细胞比较,AngⅡ组诱导的肥大心肌细胞的表面积、3H-亮氨酸掺入、心钠素、脑钠素表达显著增加(P<0.01);AngⅡ+GW0742组在终浓度为10μmol/L时可明显逆转此改变(P<0.01);同时GW0742抑制肥大心肌细胞的基质金属蛋白酶-2和基质金属蛋白酶-9、白细胞介素-1β的mRNA过度表达。结论GW0742抑制AngⅡ介导的体外心肌细胞肥大,其机制可能为通过调控炎性因子所致。
Objective To investigate the effect of activation of peroxisome peroliferator-activated receptor beta/delta （PPARβ/δ） on AngⅡ induced hypertrophic cardiomyocytes in vitro and pos sible mechanism. Methods Hypertrophy of neonatal rat cardiac myocytes （MC） in culture was induced by angiotensin Ⅱ （AngⅡ）. then the effect of GW0742 on the hypertrophy was exam ined. The cultured cells without any treatment served as normal control. The study included AngⅡ group and AngⅡ＋GW0742 group. 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 a H leucine incorporation. mRNA expression of atrial natriuretic peptide （ANP）,brain natriuretic peptide （BNP）, MMP-9, MMP-2 and IL-1β was measured by reverse transcription-polymerase chain reaction （RT-PCR）. Results AngⅡ caused the hypertrophy of cardiomyocytes,including increase in surface area.mRNA expression of ANP,BNP,MMP-9,MMP-2 and IL-1β,and ^3H-leucine incorporation. Treatment with GW0742 inhibited the above changes. Conclusion Activation of PPAR beta/ delta inhibited cardiac hypertrophy in vitro and the effect might result from controlling the inflammatory factors.
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2007年第12期847-850,共4页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
国家自然科学基金资助项目(30270551)
关键词
心肌病
肥厚性
过氧化物酶体增殖物激活受体
心钠素
利钠肽
脑
cardiomyopathy, hypertrophic
peroxisome proliferator activated receptors
atrial natriuretic factor
natriuretic peptide, brain
