心肌细胞来源NCoR1对小鼠心肌梗死损伤的保护作用

秦子涵; 陈颖敏; 卜军

doi:10.16766/j.cnki.issn.1674-4152.002126

心肌细胞来源NCoR1对小鼠心肌梗死损伤的保护作用

doi: 10.16766/j.cnki.issn.1674-4152.002126

上海交通大学医学院附属仁济医院心内科，上海 200127

基金项目:

国家自然科学基金项目 81930007

详细信息

通讯作者:
卜军, E-mail: pujun310@hotmail.com

中图分类号: R542.22 R-332
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- 被引次数: 0
出版历程
- 收稿日期: 2021-01-28
- 网络出版日期: 2022-02-15

Nuclear receptor corepressor 1 significantly attenuates myocardial infarction injury in mice

Department of Cardiology, Renji Hospital, School of Medicine, Shanghai .Jiao Tong University ，Shanghai 200127,China

摘要

摘要: 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。
- 心肌梗死 /
- 核受体辅抑制因子1 /
- 小鼠
Abstract: 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.
- Myocardial infarction /
- Nuclear receptor corepressor 1 /
- Mice

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图 1 各组小鼠心肌梗死后28 d生存率统计

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图 2 各组小鼠心肌梗死后28 d超声心动图和小动物PET/CT

注：A为Sham-WT^αMHC-Cre组；B为Sham-NCoR1^{Fl/Fl, αMHC-Cre}组；C为MI-WT^αMHC-Cre组；D为MI-NCoR1^{Fl/Fl, αMHC-Cre}组。

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图 3 各组小鼠心脏

注：A为Sham-WT^αMHC-Cre组；B为Sham-NCoR1^{Fl/Fl, αMHC-Cre}组；C为MI-WT^αMHC-Cre组；D为MI-NCoR1^{Fl/Fl, αMHC-Cre}组。

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图 4 各组小鼠心肌组织

注：A为Sham-WT^αMHC-Cre组；B为Sham-NCoR1^{Fl/Fl, αMHC-Cre}组；C为MI-WT^αMHC-Cre组；D为MI-NCoR1^{Fl/Fl, αMHC-Cre}组；各组图中第2幅图为使用Masson染色，×200；第3幅图为使用天狼星红染色，×200。

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表 1 4组小鼠心功能指标结果比较(x ±s)

组别	例数	¹⁸F-FDG摄取(MBq)	LVEF(%)	LVFS(%)	LV容积(μL)
假手术野生型组	10	3.64±0.04	54.07±1.05	27.48±0.66	58.09±2.01
假手术基因敲除组	10	3.61±0.03	53.65±1.21	27.23±0.78	66.51±2.82
心肌梗死野生型组	10	2.74±0.06^a	30.39±5.13^a	14.62±2.69^a	101.50±14.07^a
心肌梗死基因敲除组	10	1.60±0.03^bc	9.46±2.10^bc	4.26±0.96^bc	197.50±22.41^bc
F值		5 271.000	548.940	542.860	229.300
P值		＜0.001	0.017	0.020	＜0.001
注：与假手术野生型组比较，^aP＜0.05；与假手术基因敲除组比较，^bP＜0.05；与心肌梗死野生型组比较，^cP＜0.05。

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表 2 4组小鼠心肌梗死面积与纤维化程度比较(x ±s，%)

组别	例数	梗死程度	纤维化程度
假手术野生型组	4	0	0
假手术基因敲除组	4	0	0
心肌梗死野生型组	4	36.22±0.86^a	32.70±0.85^a
心肌梗死基因敲除组	4	47.17±1.27^bc	46.38±1.31^bc
t值		14.278	17.520
P值		＜0.001	＜0.001
注：与假手术野生型组比较，^aP＜0.05；与假手术基因敲除组比较，^bP＜0.05；与心肌梗死野生型组比较，^cP＜0.05。

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表 3 4组小鼠心肌标志物和炎症指标结果比较(x ±s)

组别	例数	磷酸肌酸激酶(IU/L)	乳酸脱氢酶(IU/L)	TNF-α(pg/mL)	IL-6(pg/mL)
假手术野生型组	10	188.97±22.05	201.25±45.24	2.34±0.15	2.69±0.34
假手术基因敲除组	10	189.16±28.26	251.76±36.78	2.56±0.26	2.17±0.29
心肌梗死野生型组	10	315.26±69.26^a	320.21±85.71^a	4.19±1.09^a	2.99±0.52^a
心肌梗死基因敲除组	10	463.15±110.65^bc	390.25±103.45^bc	5.06±1.27^bc	4.05±0.89^bc
F值		30.660	12.620	23.670	19.910
P值		0.034	0.019	0.027	0.022
注：与假手术野生型组比较，^aP＜0.05；与假手术基因敲除组比较，^bP＜0.05；与心肌梗死野生型组比较，^cP＜0.05。

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