LPA1杂合敲除对心梗小鼠存活及心肌重构的影响

The Effect of Heterozygous Deletion of LPA1 in Survival and Myocardial Remodeling after Myocardial Infarction in Mice

目的研究溶血磷脂酸1型受体亚型(LPA1)对心梗后存活、心肌功能及重构的影响。方法LPA1(+/-)和LPA1(+/+)小鼠建立心梗模型(MI),心梗4周后通过超声心动图检测心功能后取材。天狼猩红染色评价梗死面积和心肌纤维化,WGA染色分析心肌细胞横截面积,TUNEL染色评价心肌细胞凋亡水平。结果心梗4周后,与LPA1(+/+)心梗组相比,LPA1(+/-)小鼠的生存率较显著降低;心功能未见明显变化;心肌重构方面,梗死面积、肥大、凋亡及纤维化水平均与LPA1(+/+)小鼠MI组无显著差别。结论全身LPA1半剂量缺失致使小鼠心梗4周生存率显著降低,但不影响心梗后心肌重构和心功能。提示LPA1全身半剂量缺失可能通过心肌以外的其它途径影响其心梗后生存率。

Objective To investigate the effect of Lysophosphatidic acid type 1 receptor（LPA1）on survival, cardiac function and remodeling after MI. Methods Permanent ligation of left anterior descending （LAD） coronary artery was performed to induce MI of LPA1 （＋/-） and LPA1 （＋/-） male mice. Heart function was assessed by echocardiography at four weeks post-MI and then mice were sacrificed. Infarct size and fibrosis were assessed by Picrosirius red staining. Cardiomyoeyte cross-sectional area was assessed by WGA Immunofluoreseence staining. TUNEL experiments were conducted to detect apoptosis. Results After four weeks of MI, lower survival-rate showed up in LPA1 （＋/-） mice compared with wild-type mice （P〈0.05）. However, no obvious difference in cardiac function and infarcted area were observed between LPAI （＋/-） infarcted mice and LPA1 （＋/＋） infarcted mice. Furthermore, cardiac remodeling related indexes in LPA1 （＋/-） MI mice, namely cardiac fibrosis, cross-sectional area and apoptosis, showed no differences comparing to LPA1 （＋/＋） MI ones. Conclusions Heterozygous deletion of LPA1 reduces survival rate of MI, while it does not affect cardiac function and cardiac remodeling. These results suggest that general halfdeletion of LPA1 might not directly influence cardiac remodeling, but via affecting other systems to lower survival rate of MI.