心肌细胞来源NCoR1对小鼠心肌梗死损伤的保护作用

  目的  探究心肌细胞来源的核受体辅抑制因子1(NCoR1)对小鼠心肌梗死损伤发挥的作用。  方法  构建心肌细胞NCoR1特异性敲除小鼠并根据不同手术处理分为假手术野生型组、假手术基因敲除组、心肌梗死野生型组和心肌梗死基因敲除组，每组各50只小鼠。统计各组小鼠在心肌梗死28 d的生存率和心功能水平；通过病理染色判断梗死面积与纤维化程度；测定小鼠血清心肌酶磷酸肌酸激酶(CK-MB)、乳酸脱氢酶(LDH)]及炎症指标肿瘤坏死因子α(TNF-α)、白介素6(IL-6)]水平。  结果  与野生型小鼠相比，基因敲除组小鼠存活率更低，左心室射血分数(30.39±5.13)% vs. (9.46±2.10)%]和左心室缩短分数(14.62±2.69)% vs. (4.26±0.96)%]均明显下降，而左室容积(101.50±14.07)μL vs. (197.50±22.41)μL]明显升高(均P＜0.05)；小动物PET/CT提示心肌梗死后野生型小鼠对18F-FDG的摄取量更高(2.74±0.06)MBq vs. (1.60±0.03)MBq]，梗死程度(36.22±0.86)% vs. (47.17±1.27)%]和纤维化程度(32.70±0.85)% vs. (46.38±1.31)%]更低(均P＜0.05)；血清学指标显示敲除小鼠心肌损伤更重且炎症水平更高(均P＜0.05)。  结论  心肌细胞中NCoR1在小鼠心肌梗死中发挥重要的保护作用。 

Nuclear receptor corepressor 1 significantly attenuates myocardial infarction injury in mice

  Objective   To explore the effect of nuclear receptor corepressor 1 (NCoR1) derived from cardiomyocytes on myocardial infarction injury in mice.   Methods   Cardiomyocyte-specific NCoR1 knockout mice were constructed and divided into the sham operation wild-type group, sham operation gene knockout group, myocardial infarction wild-type group and myocardial infarction gene knockout group, with 50 mice in each group. The survival rate and cardiac function level of mice in each group at 28 days of myocardial infarction were statistically analysed. Pathological staining was used to determine the infarct area and fibrosis degree. The levels of serum myocardial enzymes (creatine kinase MB, lactate dehydrogenase) and inflammation indicators (tumor necrosis factor-α, interleukin-6) were determined.   Results   Compared with wild-type mice, the knockout group mice had lower survival rate, significantly decreased left ventricular ejection fraction (30.39±5.13)% vs. (9.46±2.10)%] and left ventricular shortening fraction (14.62±2.69)% vs. (4.26±0.96)%], and significantly increased left ventricular volume (101.50±14.07)μL vs. (197.50±22.41)μL, all P < 0.05]. Small animal PET/CT indicated that wild-type mice had higher intake of 18F-FDG after myocardial infarction (2.74±0.06)MBq vs. (1.60±0.03)MBq] and degree of infarction (36.22±0.86)% vs. (47.17±1.27)%] and degree of fibrosis (32.70±0.85)% vs. (46.38±1.31)%, all P < 0.05]. Serological indicators showed that the myocardial damage of knockout mice was more severe, and the level of inflammation was higher (all P < 0.05).   Conclusion   NCoR1 in cardiomyocytes plays an important protective role in myocardial infarction in mice.