Objective: To investigate the effect of lipid factor CTRP9 on myocardial remodeling induced by isoproterenol in mice. Methods: Male C57BL/6J mice were randomly assigned to four groups (n=10 per group), then mice were administered 5 mg/kg ISO q12h for 12 days by daily subcutaneous injection to induce myocardial remodeling model. Mice also received subcutaneous injection of CTRP9 (200 μg·kg(-1)·d(-1)) for 12days. Echocardiography was performed to compare the ventricular wall thickness and cardiac function. Heart weight/body weight (HW/BW), lung weight/body weight (LW/BW), heart weight/tibia length (HW/TL) and cross-sectional area of cardiomyocytes were compared between groups. The cardiac hypertrophic markers and fibrotic markers were also compared by RT-PCR between the two groups. Molecular protein changes were evaluated by Western blot. Results: CTRP9 was down-regulated in model group. The LVEDd (4.00 mm vs 4.67 mm), LVEDs (2.60 mm vs 3.12 mm) in mode group were both higher than control group while the LVEF (73% vs 55%) and FS (39% vs 21%) were reduced in mode group. Compared with the control group, the HW/BW, LW/BW, HW/TL and cross-sectional area of cardiomyocytes were much higher in mode group (P<0.05). The transcription level of hypertrophic markers (ANP, BNP, β-MHC) were elevated. Left ventricular collagen volume was increased as well as the transcription level of fibrosis markers collagen Ⅰ, collagen Ⅲ and a-SMA. Western blot results indicated that CTRP9 increased nNOS and eNOS derived NO production but not iNOS expression. Conclusion: CTRP9 could protect against ISO induced myocardial remodeling by increasing nNOS and eNOS derived NO production.
目的： 本试验旨在探讨CTRP9对ISO诱导的心肌重构的影响。 方法： 雄性C57BL/6J小鼠分为4组(n＝10), 5 mg/kg每12小时1次的方式和剂量皮下注射ISO 12 d，同时以200 μg·kg(－1)·d(－1)皮下注射的方式给予人重组CTRP9 12 d。免疫组化染色CTRP9的表达和细胞定位；超声心动图比较各组小鼠心室壁厚度以及心功能，评价模型组小鼠心脏结构和心功能；取心脏后比较各组小鼠心脏质量/体质量、肺脏质量/体质量、心脏质量/胫骨长；HE染色比较心肌细胞横截面积；RT-PCR检测比较各组小鼠心肌肥厚标志物和纤维化标志物的转录水平；免疫印迹评价分子蛋白的改变。 结果： 免疫组化结果显示：模型组小鼠CTRP9的表达明显下调(P<0.05)；超声结果显示：模型组小鼠左室舒张期内径(LVDd, 4.00 mm比4.67 mm)、左室收缩期内径(LVDs，2.60 mm比3.12 mm)均大于对照组(P<0.05)，而左室射血分数(LVEF，73%比55%)以及短轴缩短率(FS，39%比21%)均小于对照组(P<0.05)；模型组小鼠心脏质量/体质量、肺脏质量/体质量、心脏质量/胫骨长以及心肌细胞横截面积明显高于对照组(P<0.05)；RT-PCR结果显示模型组小鼠心肌肥厚标志物(ANP、BNP以及β-MHC)明显增高(P<0.05)；PSR染色结果显示模型组小鼠心脏纤维化程度加重，且纤维化标志物(Ⅰ型胶原，Ⅲ型胶原和α平滑肌动蛋白)的转录水平均高于对照组(P<0.05)；而CTRP9处理后心肌肥厚程度明显降低，心脏纤维化程度减轻，心功能明显改善(P<0.05)。免疫印迹结果显示：模型组小鼠心脏iNOS的表达未见改变，而nNOS和eNOS的表达有所增加，但是CTRP9进一步增加eNOS和nNOS的表达，从而增加一氧化氮的合成。 结论： CTRP9通过增加eNOS和nNOS来源的一氧化氮保护ISO诱导的心肌重构。.
Keywords: Adipose factor; Cardiac remodeling; Isoproterenol; Nitric oxide synthase.