hESC-MSCs改善猪心肺复苏后心功能障碍的作用及机制研究

doi:10.3877/cma.j.issn.1674-6880.2025.05.001

中华危重症医学杂志(电子版) ›› 2025, Vol. 18 ›› Issue (05) : 353 -361. doi: 10.3877/cma.j.issn.1674-6880.2025.05.001

论著

hESC-MSCs改善猪心肺复苏后心功能障碍的作用及机制研究

朱锦江¹^,², 徐杰丰¹, 葛风², 曹光立³, 王旭光⁴, 周梅亚⁵, 陈铁江², 张茂¹^,^†(

)

¹310009　杭州，浙江大学医学院附属第二医院急诊医学科/全省严重烧创伤诊治与应急救援重点实验室/浙江省急危重症临床医学研究中心
²322000　浙江义乌，义乌市中心医院急诊医学科
³312099　浙江绍兴，绍兴第二医院急诊医学科
⁴315000　浙江宁波，宁波市第一医院急诊医学科
⁵310003　杭州，杭州市急救中心

收稿日期:2024-10-21 出版日期:2025-10-31
通信作者: 张茂
基金资助:
浙江省重点研发计划项目(2024C04045、2021C03073); 金华市重点科技计划项目(2022-3-043); 金华市重大科技计划项目(2023-3-005)

Efficacy and mechanism of hESC-MSCs in ameliorating post-cardiopulmonary resuscitation cardiac dysfunction in pigs

Jinjiang Zhu¹^,², Jiefeng Xu¹, Feng Ge², Guangli Cao³, Xuguang Wang⁴, Meiya Zhou⁵, Tiejiang Chen², Mao Zhang¹^,^†()

¹Department of Emergency Medicine, the Second Affiliated Hospital, Zhejiang University School of Medicine/Provincial Key Laboratory of Diagnosis and Treatment of Severe Burns and Trauma/Zhejiang Provincial Clinical Research Center for Critical Illnesses and Emergencies, Hangzhou 310009, China
²Department of Emergency Medicine, Yiwu Central Hospital, Yiwu 322000, China
³Department of Emergency Medicine, Shaoxing Second Hospital, Shaoxing 312099, China
⁴Department of Emergency Medicine, Ningbo First Hospital, Ningbo 315000, China
⁵Hangzhou Emergency Center, Hangzhou 310003, China

Received:2024-10-21 Published:2025-10-31
Corresponding author: Mao Zhang

全文 ( ) 下载PDF ( ) 导出引用

引用本文：

朱锦江, 徐杰丰, 葛风, 曹光立, 王旭光, 周梅亚, 陈铁江, 张茂. hESC-MSCs改善猪心肺复苏后心功能障碍的作用及机制研究[J/OL]. 中华危重症医学杂志(电子版), 2025, 18(05): 353-361.

Jinjiang Zhu, Jiefeng Xu, Feng Ge, Guangli Cao, Xuguang Wang, Meiya Zhou, Tiejiang Chen, Mao Zhang. Efficacy and mechanism of hESC-MSCs in ameliorating post-cardiopulmonary resuscitation cardiac dysfunction in pigs[J/OL]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2025, 18(05): 353-361.

目的

探讨人胚胎干细胞来源间充质干细胞（hESC-MSCs）对猪心脏骤停（CA）复苏后心功能障碍的影响及作用机制。

方法

采用随机数字表法将27头健康雄性白猪分为假手术组（Sham组）、心肺复苏组（CPR组）与hESC-MSCs组，每组9头。Sham组仅完成外科置管相关准备；CPR组和hESC-MSCs组经右心室电极释放交流电诱发心室颤动10 min + CPR 6 min建立CA-CPR模型。复苏后成功5 min时，hESC-MSCs组经股静脉1 h内泵入2.5 × 10⁶个/kg的hESC-MSCs细胞，其余2组给予等量0.9%NaCl溶液。于复苏后2、4、8、24、48和72 h时，应用脉搏指示连续心排血量（PiCCO）监测仪检测各组的每博输出量（SV）、全心射血分数（GEF），通过酶联免疫吸附测定（ELISA）法检测心肌肌钙蛋白（cTnI）、肌酸激酶同工酶MB（CKMB）血清浓度。于复苏后24、48和72 h时，每组随机选3头猪处死并取左室心肌组织标本，应用脱氧核糖核苷酸末端转移酶介导的缺口末端标记（TUNEL）法检测各组的细胞凋亡水平，western-blotting法检测蛋白激酶R样内质网激酶（PERK）、C/EBP同源蛋白（CHOP）、半胱氨酸天冬氨酸蛋白酶12（caspase 12）和caspase 3的表达水平。

结果

复苏后2、4、8、24、48和72 h，3组实验猪的SV（F = 97.956、54.970、46.893、8.685、17.754、18.070，P均< 0.05）、GEF值（F = 219.499、95.886、43.986、15.809、16.337、8.050，P均< 0.05）、cTnI（F = 112.367、259.559、83.680、69.664、55.522、102.025，P均< 0.05）和CKMB血清浓度（F = 77.607、77.995、64.601、43.265、47.544、25.836，P均< 0.05）比较，差异均有统计学意义。与CPR组相比，hESC-MSCs组复苏后各时间点的SV和GEF值均显著升高（P均< 0.05）。3组实验猪复苏后24、48和72 h的心肌细胞凋亡指数（F = 68.585、156.766、189.283，P均< 0.001）、PERK（F = 108.029、33.089、42.870，P均< 0.001）、CHOP（F = 32.813、34.275、69.464，P均< 0.001）、caspase 12（F = 41.344、16.836、82.824，P均< 0.001）和caspase 3（F = 74.913、41.634、43.085，P均< 0.001）的蛋白表达水平比较，差异均有统计学意义。与CPR组相比，hESC-MSCs组在上述时间点的心肌细胞凋亡指数均显著减少，内质网应激凋亡相关蛋白的表达水平均显著下调（P均< 0.05）。

结论

hESC-MSCs后处理具有改善猪CA复苏后心功能障碍的保护作用，其机制可能与抑制内质网应激的凋亡途径有关。

关键词: 心脏骤停, 心肺复苏, 心功能障碍, 人胚胎干细胞来源间充质干细胞, 内质网应激, 凋亡, 猪

Objective

To investigate the effects and underlying mechanisms of human embryonic stem cell derived mesenchymal stem cells (hESC-MSCs) on post-resuscitation cardiac dysfunction in a porcine model of cardiac arrest (CA).

Methods

Twenty-seven healthy male white pigs were randomly allocated to three groups (9 pigs per group) using a random number table: a Sham group, a cardiopulmonary resuscitation (CPR) group, and an hESC-MSCs group. The Sham group only completed the preparations related to surgical catheter placement. The CA-CPR model was established by inducing ventricular fibrillation for 10 minutes via a right ventricular electrode, followed by 6 minutes of CPR in the CPR group and the hESC-MSCs group. At 5 minutes after successful resuscitation, the hESC-MSCs group received an intravenous infusion of 2.5 × 10⁶ cells/kg hESC-MSCs in 1 hour; the Sham and CPR groups received an equivalent volume of 0.9% NaCl solution. Cardiac function parameters, including stroke volume (SV) and global ejection fraction (GEF), were monitored using pulse indicator continuous cardiac output (PiCCO) at 2, 4, 8, 24, 48, and 72 hours after resuscitation, and serum concentrations of cardiac troponin I (cTnI) and creatine kinase MB (CKMB) were quantified via enzyme-linked immunosorbent assay (ELISA). At 24, 48, and 72 hours after resuscitation, three pigs per group were euthanized, and left ventricular myocardial tissue samples were collected. Myocardial apoptosis was assessed using TdT-mediated dUTP nick labeling (TUNEL). Expression levels of protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), cysteinyl aspartate specific proteinase 12 (caspase 12), and caspase 3 were determined via western-blotting.

Results

Significant differences were observed in SV (F = 97.956, 54.970, 46.893, 8.685, 17.754, 18.070; all P < 0.05), GEF (F = 219.499, 95.886, 43.986, 15.809, 16.337, 8.050; all P < 0.05), serum cTnI (F = 112.367, 259.559, 83.680, 69.664, 55.522, 102.025; all P < 0.05), and serum CKMB (F = 77.607, 77.995, 64.601, 43.265, 47.544, 25.836; all P < 0.05) among the three groups at all post-resuscitation time points (2, 4, 8, 24, 48, and 72 hours). Compared with the CPR group, the hESC-MSCs group demonstrated significantly higher SV and GEF at all post-resuscitation time points (all P < 0.05). Significant differences were also observed in the myocardial apoptosis index (F = 68.585, 156.766, 189.283; all P < 0.001) and protein expression of PERK (F = 108.029, 33.089, 42.870; all P < 0.001), CHOP (F = 32.813, 34.275, 69.464; all P < 0.001), caspase 12 (F = 41.344, 16.836, 82.824; all P < 0.001), and caspase 3 (F = 74.913, 41.634, 43.085; all P < 0.001) among the three groups at 24, 48, and 72 hours after resuscitation. Compared with the CPR group, the hESC-MSCs group showed significantly reduced myocardial apoptosis index and downregulated expression of endoplasmic reticulum (ER) stress-related apoptotic proteins at the same time points (all P < 0.05).

Conclusion

Post-resuscitation treatment with hESC-MSCs ameliorates cardiac dysfunction in a porcine CA model, potentially via inhibition of ER stress-induced apoptotic pathways.

Key words: Cardiac arrest, Cardiopulmonary resuscitation, Cardiac dysfunction, Mesenchymal stem cells derived from human embryonic stem cells, Endoplasmic reticulum stress, Apoptosis, Pig

表1 3组实验猪的基线状态比较（

± s）

组别	只数	体质量（kg）	心率（次/min）	平均动脉压（mmHg）	呼气末二氧化碳分压（mmHg）	pH值	乳酸（mmol/L）
Sham组	9	39.0 ± 1.7	83 ± 4	108 ± 8	38.7 ± 1.5	7.49 ± 0.03	1.2 ± 0.5
CPR组	9	38.4 ± 2.2	83 ± 6	103 ± 8	37.7 ± 0.7	7.51 ± 0.04	1.4 ± 0.4
hESC-MSCs组	9	39.0 ± 1.1	83 ± 5	103 ± 7	38.1 ± 1.8	7.52 ± 0.04	1.1 ± 0.4
F值		0.308	0.006	1.253	1.109	2.015	0.658
P值		0.738	0.994	0.304	0.346	0.155	0.527

表1 3组实验猪的基线状态比较（

± s）

组别	只数	体质量（kg）	心率（次/min）	平均动脉压（mmHg）	呼气末二氧化碳分压（mmHg）	pH值	乳酸（mmol/L）
Sham组	9	39.0 ± 1.7	83 ± 4	108 ± 8	38.7 ± 1.5	7.49 ± 0.03	1.2 ± 0.5
CPR组	9	38.4 ± 2.2	83 ± 6	103 ± 8	37.7 ± 0.7	7.51 ± 0.04	1.4 ± 0.4
hESC-MSCs组	9	39.0 ± 1.1	83 ± 5	103 ± 7	38.1 ± 1.8	7.52 ± 0.04	1.1 ± 0.4
F值		0.308	0.006	1.253	1.109	2.015	0.658
P值		0.738	0.994	0.304	0.346	0.155	0.527

表2 3组实验猪复苏前后心脏功能SV比较（mL，

± s）

组别	只数	复苏前	复苏后2 h	复苏后4 h	复苏后8 h	复苏后24 h	复苏后48 h	复苏后72 h
Sham组	9	46.7 ± 4.1	43.7 ± 3.7	43.7 ± 3.6	46.0 ± 3.4	41.0 ± 2.6	45.7 ± 1.2	42.0 ± 4.6
CPR组	9	46.0 ± 2.9	20.0 ± 3.2^a	22.6 ± 2.8^a	26.1 ± 3.9^a	27.7 ± 6.7^a	28.0 ± 4.4^a	26.3 ± 5.7^a
hESC-MSCs组	9	48.1 ± 2.6	27.6 ± 4.1^ab	33.7 ± 5.8^ab	38.6 ± 5.6^ab	44.0 ± 5.2^b	42.3 ± 4.9^b	48.0 ± 3.0^b
F值		0.995	97.956	54.970	46.893	8.685	17.754	18.070
P值		0.385	<0.001	<0.001	<0.001	0.017	0.003	0.003

表2 3组实验猪复苏前后心脏功能SV比较（mL，

± s）

组别	只数	复苏前	复苏后2 h	复苏后4 h	复苏后8 h	复苏后24 h	复苏后48 h	复苏后72 h
Sham组	9	46.7 ± 4.1	43.7 ± 3.7	43.7 ± 3.6	46.0 ± 3.4	41.0 ± 2.6	45.7 ± 1.2	42.0 ± 4.6
CPR组	9	46.0 ± 2.9	20.0 ± 3.2^a	22.6 ± 2.8^a	26.1 ± 3.9^a	27.7 ± 6.7^a	28.0 ± 4.4^a	26.3 ± 5.7^a
hESC-MSCs组	9	48.1 ± 2.6	27.6 ± 4.1^ab	33.7 ± 5.8^ab	38.6 ± 5.6^ab	44.0 ± 5.2^b	42.3 ± 4.9^b	48.0 ± 3.0^b
F值		0.995	97.956	54.970	46.893	8.685	17.754	18.070
P值		0.385	<0.001	<0.001	<0.001	0.017	0.003	0.003

表3 3组实验猪复苏前后心脏功能GEF比较（%，

± s）

组别	只数	复苏前	复苏后2 h	复苏后4 h	复苏后8 h	复苏后24 h	复苏后48 h	复苏后72 h
Sham组	9	36.8 ± 3.2	35.9 ± 1.9	36.7 ± 2.5	36.7 ± 3.1	37.0 ± 3.0	38.7 ± 2.3	35.3 ± 1.2
CPR组	9	38.1 ± 3.8	16.8 ± 1.7^a	18.9 ± 1.3^a	22.3 ± 1.9^a	24.7 ± 3.2^a	24.0 ± 3.0^a	26.0 ± 5.3^a
hESC-MSCs组	9	39.2 ± 4.6	22.8 ± 2.3^ab	26.6 ± 3.8^ab	29.4 ± 4.3^ab	37.3 ± 3.2^b	34.7 ± 4.2^b	35.7 ± 2.1^b
F值		0.874	219.499	95.886	43.986	15.809	16.337	8.050
P值		0.430	<0.001	<0.001	<0.001	0.004	0.004	0.003

表3 3组实验猪复苏前后心脏功能GEF比较（%，

± s）

组别	只数	复苏前	复苏后2 h	复苏后4 h	复苏后8 h	复苏后24 h	复苏后48 h	复苏后72 h
Sham组	9	36.8 ± 3.2	35.9 ± 1.9	36.7 ± 2.5	36.7 ± 3.1	37.0 ± 3.0	38.7 ± 2.3	35.3 ± 1.2
CPR组	9	38.1 ± 3.8	16.8 ± 1.7^a	18.9 ± 1.3^a	22.3 ± 1.9^a	24.7 ± 3.2^a	24.0 ± 3.0^a	26.0 ± 5.3^a
hESC-MSCs组	9	39.2 ± 4.6	22.8 ± 2.3^ab	26.6 ± 3.8^ab	29.4 ± 4.3^ab	37.3 ± 3.2^b	34.7 ± 4.2^b	35.7 ± 2.1^b
F值		0.874	219.499	95.886	43.986	15.809	16.337	8.050
P值		0.430	<0.001	<0.001	<0.001	0.004	0.004	0.003

表4 3组实验猪复苏前后心肌损伤标志物cTnI水平比较（ng/L，

± s）

组别	只数	复苏前	复苏后2 h	复苏后4 h	复苏后8 h	复苏后24 h	复苏后48 h	复苏后72 h
Sham组	9	133 ± 26	128 ± 43	121 ± 53	175 ± 60	161 ± 32	142 ± 18	168 ± 58
CPR组	9	151 ± 49	475 ± 57^a	536 ± 30^a	635 ± 110^a	819 ± 103^a	645 ± 99^a	644 ± 17^a
hESC-MSCs组	9	147 ± 47	388 ± 47^ab	405 ± 32^ab	433 ± 39^ab	643 ± 58^a	435 ± 18^ab	421 ± 36^ab
F值		0.467	112.367	259.559	83.680	69.664	55.522	102.025
P值		0.632	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

表4 3组实验猪复苏前后心肌损伤标志物cTnI水平比较（ng/L，

± s）

组别	只数	复苏前	复苏后2 h	复苏后4 h	复苏后8 h	复苏后24 h	复苏后48 h	复苏后72 h
Sham组	9	133 ± 26	128 ± 43	121 ± 53	175 ± 60	161 ± 32	142 ± 18	168 ± 58
CPR组	9	151 ± 49	475 ± 57^a	536 ± 30^a	635 ± 110^a	819 ± 103^a	645 ± 99^a	644 ± 17^a
hESC-MSCs组	9	147 ± 47	388 ± 47^ab	405 ± 32^ab	433 ± 39^ab	643 ± 58^a	435 ± 18^ab	421 ± 36^ab
F值		0.467	112.367	259.559	83.680	69.664	55.522	102.025
P值		0.632	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

表5 3组实验猪复苏前后心肌损伤标志物CKMB水平比较（ng/L，

± s）

组别	只数	复苏前	复苏后2 h	复苏后4 h	复苏后8 h	复苏后24 h	复苏后48 h	复苏后72 h
Sham组	9	30 ± 16	36 ± 9	27 ± 14	29 ± 17	35 ± 13	30 ± 15	34 ± 14
CPR组	9	34 ± 14	87 ± 9^a	115 ± 20^a	124 ± 17^a	146 ± 18^a	122 ± 17^a	114 ± 14^a
hESC-MSCs组	9	34 ± 12	65 ± 9^ab	71 ± 10^ab	75 ± 19^ab	92 ± 11^ab	92 ± 12^ab	94 ± 16^a
F值		0.216	77.607	77.995	64.601	43.265	47.544	25.836
P值		0.807	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

表5 3组实验猪复苏前后心肌损伤标志物CKMB水平比较（ng/L，

± s）

组别	只数	复苏前	复苏后2 h	复苏后4 h	复苏后8 h	复苏后24 h	复苏后48 h	复苏后72 h
Sham组	9	30 ± 16	36 ± 9	27 ± 14	29 ± 17	35 ± 13	30 ± 15	34 ± 14
CPR组	9	34 ± 14	87 ± 9^a	115 ± 20^a	124 ± 17^a	146 ± 18^a	122 ± 17^a	114 ± 14^a
hESC-MSCs组	9	34 ± 12	65 ± 9^ab	71 ± 10^ab	75 ± 19^ab	92 ± 11^ab	92 ± 12^ab	94 ± 16^a
F值		0.216	77.607	77.995	64.601	43.265	47.544	25.836
P值		0.807	<0.001	<0.001	<0.001	<0.001	<0.001	<0.001

图1 3组实验猪复苏后24、48和72 h心肌组织细胞凋亡情况的比较（每组n = 3）注：Sham.假手术；CPR.心肺复苏；hESC-MSCs.人胚胎干细胞来源间充质干细胞；TUNEL.脱氧核糖核苷酸末端转移酶介导的缺口末端标记；与Sham组比较，^aP < 0.05；与CPR组比较，^bP < 0.05（TUNEL染色　× 200）

图2 3组实验猪复苏后24、48和72 h心肌组织PERK、CHOP、caspase 12和caspase 3蛋白表达水平的变化（每组n = 3）注：PERK.蛋白激酶R样内质网激酶；CHOP. C/EBP同源蛋白；caspase 12.半胱氨酸天冬氨酸蛋白酶12；GAPDH.磷酸甘油醛脱氢酶；Sham.假手术；CPR.心肺复苏；hESC-MSCs.人胚胎干细胞来源间充质干细胞；与Sham组比较，^aP < 0.05；与CPR组比较，^bP < 0.05

1	Myat A, Song KJ, Rea T. Out-of-hospital cardiac arrest: current concepts[J]. Lancet, 2018, 391 (10124): 970-979.
2	Xu F, Zhang Y, Chen Y. Cardiopulmonary resuscitation training in China: current situation and future development[J]. JAMA Cardiol, 2017, 2 (5): 469-470.
3	Tsao CW, Aday AW, Almarzooq ZI, et al. Heart disease and stroke statistics-2023 update: a report from the American Heart Association[J]. Circulation, 2023, 147 (8): e93-e621.
4	Moens AL, Claeys MJ, Timmermans JP, et al. Myocardial ischemia/reperfusion-injury, a clinical view on a complex pathophysiological process[J]. Int J Cardiol, 2005, 100 (2): 179-190.
5	Xiang M, Lu Y, Xin L, et al. Role of oxidative stress in reperfusion following myocardial ischemia and its treatments[J]. Oxid Med Cell Longev, 2021, 2021, 6614009.
6	Huang L, Yang L, Ding Y, et al. Human umbilical cord mesenchymal stem cells-derived exosomes transfers microRNA-19a to protect cardiomyocytes from acute myocardial infarction by targeting SOX6[J]. Cell Cycle, 2020, 19 (3): 339-353.
7	Xu J, Zhang M, Liu F, et al. Mesenchymal stem cells alleviate post-resuscitation cardiac and cerebral injuries by inhibiting cell pyroptosis and ferroptosis in a swine model of cardiac arrest[J]. Front Pharmacol, 2021, 12: 793829.
8	Tian G, Li J, Zhou L. Ginsenoside Rg1 regulates autophagy and endoplasmic reticulum stress via the AMPK/mTOR and PERK/ATF4/CHOP pathways to alleviate alcohol-induced myocardial injury[J]. Int J Mol Med, 2023, 52 (1): 56.
9	Zuo MY, Tang TJ, Wang X, et al. Atractylenolide III attenuates apoptosis in H9c2 cells by inhibiting endoplasmic reticulum stress through the GRP78/PERK/CHOP signaling pathway[J]. Evid Based Complement Alternat Med, 2022, 2022: 1149231.
10	葛风，徐杰丰，朱锦江，等.人胚胎干细胞来源间充质干细胞减轻心搏骤停猪复苏后脑损伤的作用机制研究[J].中华危重病急救医学，2025，37（2）：133-139.
11	邵雪波，余倩，唐卫东，等.丙戊酸钠减轻猪心肺复苏后心脑损伤的作用及机制研究[J].中华急诊医学杂志，2022，31（12）：1673-1679.
12	徐杰丰，叶森，王茉莉，等.长时程猪室颤心脏骤停模型的建立与评价[J].中华急诊医学杂志，2015，24（10）：1135-1140.
13	曹光立，高贵锋，徐杰丰，等.按压自主同步通气模式对猪心肺复苏效果影响的研究[J].中华急诊医学杂志，2024，33（9）：1257-1264.
14	Xu J, Zhao X, Jiang X, et al. Tubastatin a improves post-resuscitation myocardial dysfunction by inhibiting NLRP3-mediated pyroptosis through enhancing transcription factor EB signaling[J]. J Am Heart Assoc, 2022, 11 (7): e024205.
15	金晓胜，蔡文伟，叶侃，等. 2015心肺复苏指南新变化与进展[J].中国医师杂志，2016，18（增刊）：226-229.
16	徐杰丰.心肺复苏中新型降温和主动脉球囊阻断技术优化的实验研究[D].杭州：浙江大学，2019.
17	张龚平，谢璐涛，卢晓驰，等.萝卜硫素对猪心肺复苏后急性肺损伤的保护作用及机制[J].中国急救医学，2023，43（5）：393-398.
18	Naji A, Eitoku M, Favier B, et al. Biological functions of mesenchymal stem cells and clinical implications[J]. Cell Mol Life Sci, 2019, 76 (17): 3323-3348.
19	Mushahary D, Spittler A, Kasper C, et al. Isolation, cultivation, and characterization of human mesenchymal stem cells[J]. Cytometry A, 2018, 93 (1): 19-31.
20	Ma S, Xe N, Li W, et al. Immunobiology of mesenchymal stem cells[J]. Cell Death Differ, 2014, 21 (2): 216-225.
21	Chou SH, Lin SZ, Kuo WW, et al. Mesenchymal stem cell insights:prospects in cardiovascular therapy[J]. Cell Transplant, 2014, 23 (4-5): 513-529.
22	Lalu MM, Montroy J, Dowlatshahi D, et al. From the lab to patients: a systematic review and meta-analysis of mesenchymal stem cell therapy for stroke[J]. Transl Stroke Res, 2020, 11 (3): 345-364.
23	Mathiasen AB, Qayyum AA, Jorgensen E, et al. Bone marrow-derived mesenchymal stromal cell treatment in patients with severe ischaemic heart failure: a randomized placebo-controlled trial (MSC-HF trial)[J]. Eur Heart J, 2015, 36 (27): 1744-1753.
24	Tripathi H, Domingues A, Donahue R, et al. Combined transplantation of human MSCs and ECFCs improves cardiac function and decrease cardiomyocyte apoptosis after acute myocardial infarction[J]. Stem Cell Rev Rep, 2023, 19 (2): 573-577.
25	Wu J, Song D, Li Z, et al. Immunity-and-matrix-regulatory cells derived from human embryonic stem cells safely and effectively treat mouse lung injury and fibrosis[J]. Cell Res, 2020, 30 (9): 794-809.
26	Bendixen E, Danielsen M, Larsen K, et al. Advances in porcine genomics and proteomics-a toolbox for developing the pig as a model organism for molecular biomedical research[J]. Brief Funct Genomics, 2010, 9 (3): 208-219.
27	Lunney JK, Van Goor A, Walker KE, et al. Importance of the pig as a human biomedical model[J]. Sci Transl Med 2021, 13 (621): eabd5758.
28	Fischer UM, Cox CS Jr, Laine GA, et al. Induction of cardioplegic arrest immediately activates the myocardial apoptosis signal pathway[J]. Am J Physiol Heart Circ Physiol, 2007, 292 (3): H1630-H1633.
29	Hetz C, Zhang K, Kaufman RJ. Mechanisms, regulation and functions of the unfolded protein response[J]. Nat Rev Mol Cell Biol, 2020, 21 (8): 421-438.
30	Ren J, Bi Y, Sowers JR, et al. Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases[J]. Nat Rev Cardiol 2021, 18 (7): 499-521.
31	Zhu H, Zhou H. Novel insight into the role of endoplasmic reticulum stress in the pathogenesis of myocardial ischemia-reperfusion injury[J]. Oxid Med Cell Longev, 2021, 2021: 5529810.
32	Omidkhoda N, Wallace Hayes A, Reiter RJ, et al. The role of MicroRNAs on endoplasmic reticulum stress in myocardial ischemia and cardiac hypertrophy[J]. Pharmacol Res, 2019, 150: 104516.
33	Hu H, Tian M, Ding C, et al. The C/EBP homologous protein (CHOP) transcription factor functions in endoplasmic reticulum stress-induced apoptosis and microbial infection[J]. Front Immunol, 2019, 9: 3083.
34	Wang SZ, Bian WS, Zhen J, et al. Melatonin-mediated pak2 activation reduces cardiomyocyte death through suppressing hypoxia reoxygenation injury-induced endoplasmic reticulum stress[J]. J Cardiovasc Pharm, 2019, 74 (1): 20-29.
35	Yin XL, Zhang W, Yang Y, et al. Increasing expression of (CCAAT enhancer binding protein) homologous protein induced by endoplasmic reticulum stress in myocardium after cardiac arrest and resuscitation in rat[J]. Resuscitation, 2012, 83 (3): 378-385.
36	Kaur H, Sarmah D, Veeresh P, et al. Endovascular stem cell therapy post stroke rescues neurons from endoplasmic reticulum stress-induced apoptosis by modulating brain-derived neurotrophic factor/tropomyosin receptor kinase B signaling[J]. ACS Chem Neurosci, 2021, 12 (19): 3745-3759.
37	Gu C, Li H, Wang C, et al. Bone marrow mesenchymal stem cells decrease CHOP expression and neuronal apoptosis after spinal cord injury[J]. Neurosci Lett, 2017, 636: 282-289.

[1]	蒋树云, 马志军, 张旭, 陈棋帅, 耿智华贞. R-spondin 2在乳腺癌中的表达及其对SKBR-3细胞生长转移能力的影响[J/OL]. 中华乳腺病杂志(电子版), 2025, 19(05): 267-274.
[2]	马小杰, 张贵慧, 李润泽, 王秋入, 陈带领, 马清伟, 张磊, 陈长军. 对硒代甲硫氨酸逆转糖皮质激素介导的成骨细胞凋亡和成骨阻抑治疗大鼠激素性股骨头坏死的机制探索[J/OL]. 中华损伤与修复杂志(电子版), 2025, 20(05): 412-420.
[3]	丁天宇, 白新娜, 王雅丽, 申婷, 张剑英. 口腔-神经疾病研究中的秀丽隐杆线虫阿尔茨海默病模型转录组特征分析[J/OL]. 中华口腔医学研究杂志(电子版), 2025, 19(03): 160-169.
[4]	戴自强, 杜保罗, 任志鹏, 王欢, 张根, 李尚轩, 何东升, 崔官正, 李欣, 潘登科, 李巅远. 基因编辑猪-恒河猴异种心脏移植免疫抑制方案实验研究[J/OL]. 中华移植杂志(电子版), 2025, 19(03): 145-151.
[5]	任志鹏, 王欢, 戴自强, 李尚轩, 张根, 杜保罗, 何东升, 崔官正, 张佳恒, 李欣, 李巅远, 潘登科. 并联式异种心脏移植基因编辑猪-恒河猴动物模型围手术期管理经验[J/OL]. 中华移植杂志(电子版), 2025, 19(03): 189-192.
[6]	王杰艳, 胡博文, 梁辉. 细胞死亡在肾缺血再灌注损伤中的研究进展[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(05): 653-657.
[7]	谭子诚, 黄冬梅, 何春秀, 钟山. 成人俯卧位通气患者心肺复苏的研究进展[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(04): 654-656.
[8]	周玲, 肖颖, 李秋诗, 陈兆毅, 李琪, 吴园明. 亚麻木酚素通过circRNA HIPK3影响非小细胞肺癌A549 细胞凋亡及铁死亡的机制研究[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(03): 362-368.
[9]	郭依丹, 王军, 朱祥, 吉泽, 王蓓娟. TWEAK 在诱导痰中的表达与哮喘严重程度的关联性探讨[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(03): 375-379.
[10]	李杰, 冉永红, 郝玉徽. miR-21 靶向环腺苷酸应答元件结合蛋白样蛋白2 加重放射性肺纤维化的作用机制[J/OL]. 中华肺部疾病杂志(电子版), 2025, 18(02): 220-225.
[11]	曹森明, 陈欣然, 张弛, 冯毅, 李修彬, 樊文梅, 马鑫. IFI6通过抑制凋亡促进肾细胞癌进展并增强舒尼替尼耐药[J/OL]. 中华细胞与干细胞杂志(电子版), 2025, 15(05): 257-265.
[12]	张广权, 洪生杰, 陈显育, 王继才, 翟航, 吴芬芳, 史宪杰. 生物信息学分析内质网应激相关基因在非酒精性脂肪性肝炎发病中的作用[J/OL]. 中华肝脏外科手术学电子杂志, 2025, 14(05): 761-769.
[13]	黄菊, 王猛, 韩冬. 双氢青蒿素通过JAK2/STAT3信号通路调节结直肠癌细胞的增殖、迁移、凋亡和免疫相关分子研究[J/OL]. 中华结直肠疾病电子杂志, 2025, 14(04): 319-332.
[14]	徐弢, 张丽蓉, 连红强. PERK在神经退行性变性疾病中作用机制的研究进展[J/OL]. 中华脑科疾病与康复杂志(电子版), 2025, 15(05): 298-302.
[15]	王美琴, 潘海涛, 陈祥菲, 吴婉, 周昱和, 王砚青. S100B 蛋白在心血管疾病中的研究进展[J/OL]. 中华临床医师杂志(电子版), 2025, 19(03): 229-233.

阅读次数

全文

摘要

选择文件类型/文献管理软件名称

选择包含的内容

Efficacy and mechanism of hESC-MSCs in ameliorating post-cardiopulmonary resuscitation cardiac dysfunction in pigs

模态框（Modal）标题

选择文件类型/文献管理软件名称

选择包含的内容

Efficacy and mechanism of hESC-MSCs in ameliorating post-cardiopulmonary resuscitation cardiac dysfunction in pigs