肝X受体信号通路在小鼠HL-1心肌细胞肥大中的作用  

Effect of liver X receptor agonist T0901317 on endothelin-1 induced murine HL-1 cardiomyocytes hypertrophy

作　　者：李江[1] 邓春 顾文娟[1] 聂赛[1] 彭道泉[1] 赵水平[1] 

机构地区：[1]中南大学湘雅二医院心内科,长沙410011 [2]海南省海口市解放军第一八七中心医院心内科

出　　处：《中华心血管病杂志》2012年第2期161-165,共5页Chinese Journal of Cardiology

摘　　要：目的 探讨肝X受体（LXR）信号通路在内皮素-1（ET-1）诱导的小鼠HL-1心肌细胞肥大中的作用.方法 将培养的小鼠HL-1心肌细胞分为4组：（1）对照组：加入DMSO；（2）T0901317组：加入LXR受体激动剂T0901317（终浓度为1μmol/L）；（3）ET-1组：加入ET-1（终浓度1 nmol/L）诱导心肌细胞肥大；（4）T0901317＋ ET-1组：先加入T0901317（终浓度1μmol/L）处理8h后,再加入ET-1（终浓度1 nmol/L）.采用免疫荧光技术进行细胞染色,NIH图像J处理软件分析细胞表面积,3H-亮氨酸的掺入检测心肌细胞蛋白合成速率,实时定量PCR法检测心钠肽（ANP）及β-肌球蛋白重链（β-MyHC） mRNA的表达水平,并观察沉默LXR表达后T0901317对ANP mRNA表达的影响.结果 ET-1组HL-1心肌细胞相对细胞表面积、ANP、β-MyHC mRNA表达以及3H-亮氨酸的掺入分别为2.00±0.29、1.98±0.47、2.13 ±0.39和1.79 ±0.17,均显著高于对照组的1.00 ±0.26、1.00±0.21、1.00±0.31和1.00 ±0.03（P均＜0.05）.T0901317＋ ET-1组心肌细胞相对细胞表面积、ANP、β-MyHC mRNA表达及3H-亮氨酸的掺人分别为1.24±0.25、1.19 ±0.21、1.48±0.27和1.15 ±0.11,均显著低于ET-1组（P均＜0.05）,沉默LXR α/β后T0901317＋ET-1组ANP的mRNA表达为1.78±0.05,与ET-1组1.94 ±0.17比较差异无统计学意义.结论 LXR激动剂T0901317可抑制ET-1诱导的HL-1细胞的肥大,T0901317对ANP mRNA表达的抑制是受体依赖性的.Objective To investigate the role of liver X receptors （LXRs） on endothelin-1 （ ET-1 ）induced murine HL-1 cardiomyocytes hypertrophy.Methods Cutured murine HL-1 cardiomyocytes were divided into four experiment groups：①Control group：treated with DMSO ; ②T0901317 group：treated with LXRs agonist T0901317（ 1 μmol/L） ; ③ET-1 group：treated with ET-1 （ 1 nmoL/L） ; ④T0901317 ＋ ET-1 group：treated with T0901317 （ 1 μmol/L） for 8 hours,then treated with ET-1 （ 1 nmol/L）.Twenty-four hours later,immunofluorescent staining was performed on HL-1 cells,the surface area of HL-1 cells was analyzed with NIH Image J software,and the synthetic rate of protein in HL-1 cells was detected by 3 H-leucine incorporation.The mRNA level of atrial natriuretic peptide （ANP） and β-myosin heavy chain （β-MyHC ） was measured by quantitative realtime PCR.The effect of T0901317 on mRNA expression of ANP was also detected after LXRs gene silencing.Results The surface area of HL-1 cells,mRNA expression of ANP and β-MyHC,and 3H-leucine incorporation in ET-1 group were 2.00 ± 0.29,1.98 ± 0.47,2.13 ±0.39 and 1.79 ±0.17,respectively,which were singnficantly higher than those of control group （ 1.00 ±0.26,1.00 ±0.21,1.00 ±0.31 and 1.00 ±0.03,respectively,all P 〈0.05）.Compared with ET-1 group,the surface area of HL-1 cells,mRNA expression of ANP and β-MyHC,and 3H-leucine incorporation were significantly decreased in T0901317 ＋ ET-1 group （ 1.24 ± 0.25,1.19 ± 0.21,1.48 ± 0.27 and 1.15 ±0.11,respectively,all P 〈 0.05 ）.After inhibition of LXRo/β expression in HL-1 cardiomyocytes using the specific siRNAs,the mRNA expression of ANP in T0901317 ＋ ET-1 group was 1.78 ± 0.05,which was similar as that in ET-1 group （ 1.94 ± 0.17,P 〉 0.05）.Conclusion T0901317,an agonist of LXRs,could inhibit ET-1 induced cardiac hypertrophy in vitro,and LXR Iigand-mediated inhibition on ANP mRNA expression by T0901317 is receptor dependent.

关 键 词：心肌疾病 内皮缩血管肽1 肝X受体 

分 类 号：R363[医药卫生—病理学]