摘要目的 研究肝脏X受体(LXR)在肥厚心肌中表达的变化及其对心肌细胞肥大性生长的影响.方法 8周龄的野生型小鼠随机分为2组,即手术组和假手术组.两组小鼠分别接受主动脉缩窄术或假手术,术后2周进行各项指标检测,如心脏重/体重、心肌组织病理检测、分子生物学检测等;同时进行乳鼠心肌细胞体外培养,用血管紧张素(Ang)Ⅱ诱导心肌细胞肥大性生长,并与LXR激动剂T0901317共孵育,通过检测心肌细胞蛋白质合成率、分析细胞形态及肥大基因表达等,探讨LXR对体外心肌细胞肥大性生长的调控作用.结果 病理及分子生物学检测证实主动脉缩窄术成功的构建了心肌肥厚的小鼠模型.手术组小鼠心肌组织中LXRα的蛋白及mRNA表达均显著高于假手术组(P均<0.05),而LXRB的表达差异无统计学意义.体外研究表明,LXR激动剂T0901317呈剂量依赖性地抑制由AngⅡ诱导的心肌细胞肥大,表现在T0901317治疗组的心肌细胞面积、肥大基因的表达量、蛋白质合成率等均低于空白对照组(P均<0.05).结论 LXR是心肌肥厚的重要调控因子,LXR的激活能负性调控心肌细胞肥大性生长.

abstractsObjective To investigate the expression of liver X receptors ( LXR ) in hypertrophic myocardium and the effect of LXR agonist T0901317 on angiotensin Ⅱ ( Ang Ⅱ) induced cardiomyocyte hypertrophy. Methods Transverse aortic coarctation (TAC) or sham operation were performed in 2-month-old wide type mice ( C57/B6). Two weeks later, the expression of LXR in myocardium was detected by quantitative real-time PCR analysis and Western blot analysis. The effect of LXR agonist T0901317 on Ang Ⅱ -induced hypertrophy in cultured neonatal rat cardiomyocytes was also assessed. Results Quantitative real-time PCR analysis and Western blot analysis showed that LXRα but not LXRβ expression was upregulated post TAC both at mRNA and protein levels (All P < 0. 05 ). Ang Ⅱ induced increased [~3H]leucine incorporation and cardiomyocyte hypertrophy were significantly reduced by T0901317 in a dose-dependent manner (P<0.05). T0901317 also dose-dependently inhibited atrial natriuretic peptide (ANP) gene expression in cardiomyocytes ( P < 0. 05 ). Conclusion Our findings strongly suggest that LXR is a potent mediator of cardiomyocyte hypertrophy and LXR activation could attenuate Ang Ⅱ induced cardiomyocyte hypertrophy in vitro.