适度提高血钾浓度可改善心肺复苏大鼠脑组织线粒体功能

doi:10.11958/20221699

天津医药 ›› 2023, Vol. 51 ›› Issue (7): 724-728.doi: 10.11958/20221699

适度提高血钾浓度可改善心肺复苏大鼠脑组织线粒体功能

石佳欣¹(), 李诺², 杨叶桂¹^,^△(), 方卫¹, 覃斯娜¹, 黄京菊¹, 陈蒙华¹

1 广西医科大学第二附属医院重症医学科（邮编530007）
2 广西医科大学

收稿日期:2022-10-24 修回日期:2023-03-17 出版日期:2023-07-15 发布日期:2023-07-18
通讯作者: ^△杨叶桂 E-mail:89474053@qq.com
作者简介:石佳欣（1990），女，主治医师，主要从事心肺复苏方面研究。E-mail：414816268@qq.com
基金资助:
国家自然科学基金资助项目(82072128);广西自然科学基金项目(2018GXNSFBA281045)

Moderately elevating blood potassium concentration can improve mitochondrial function of brain tissue in cardiopulmonary resuscitation rats

SHI Jiaxin¹(), LI Nuo², YANG Yegui¹^,^△(), FANG Wei¹, QIN Sina¹, HUANG Jingju¹, CHEN Menghua¹

1 The Intensive Care Unit of the Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China
2 Guangxi Medical University

Received:2022-10-24 Revised:2023-03-17 Published:2023-07-15 Online:2023-07-18
Contact: ^△YANG Yegui E-mail:89474053@qq.com

石佳欣, 李诺, 杨叶桂, 方卫, 覃斯娜, 黄京菊, 陈蒙华. 适度提高血钾浓度可改善心肺复苏大鼠脑组织线粒体功能[J]. 天津医药, 2023, 51(7): 724-728.

SHI Jiaxin, LI Nuo, YANG Yegui, FANG Wei, QIN Sina, HUANG Jingju, CHEN Menghua. Moderately elevating blood potassium concentration can improve mitochondrial function of brain tissue in cardiopulmonary resuscitation rats[J]. Tianjin Medical Journal, 2023, 51(7): 724-728.

摘要/Abstract

摘要：

目的探讨心肺复苏（CPR）时适度提高血钾浓度能否改善脑组织线粒体功能。方法 80只SD大鼠随机分为假手术组（SH组）、生理盐水组（NS组）及氯化钾低（LK组）、中（MK组）和高剂量组（HK组），每组16只。经食道电刺激诱导心室颤动建立心跳骤停（CA）/CPR模型。CA后6 min启动CPR，同时经静脉注射生理盐水或氯化钾。观察并记录自主循环恢复（ROSC）后平均动脉压（MAP）、血钾，以及ROSC后24 h的神经功能缺损评分（NDS）、海马组织HE染色的细胞形态、海马组织ATP含量、Na⁺/K⁺-ATP酶活性、呼吸链复合物Ⅰ/Ⅱ/Ⅲ/Ⅳ的活性。结果与NS组相比，MK组、HK组ROSC后1 min、10 min血钾升高（P<0.05）。与NS组相比，MK组复苏后MAP变化差异无统计学意义，ROSC后24 h NDS升高（P<0.05），而HK组ROSC后8 min内的MAP明显下降（P<0.05），ROSC后24 h NDS无改善。与NS组相比，LK组海马组织呼吸链复合物Ⅲ活性升高，ATP生成增加（P<0.05）；与NS组相比，MK组ROSC后24 h呼吸链复合物Ⅰ/Ⅱ/Ⅲ活性升高，ATP生成增加、Na⁺/K⁺-ATP酶活性升高（P<0.05），ROSC后24 h海马区细胞形态改善；与NS组相比，HK组呼吸链复合物Ⅲ活性升高（P<0.05）。MK组各评估指标改善最明显。结论 CPR早期适度升高血钾可改善脑组织线粒体功能，减轻脑缺血再灌注损伤。

关键词: 氯化钾, 心肺复苏术, 再灌注损伤, 线粒体, 电子转运, 复合体

Abstract:

Objective To explore whether moderately hyperkalemia can improve mitochondrial function of brain tissue during cardiopulmonary resuscitation (CPR) in rats. Methods Eighty rats were randomly divided into five groups: the sham (SH) group, the normal saline (NS) group, the low dosage of potassium chloride (LK) group, the mid-dosage of potassium chloride (MK) group and the high-dosage of potassium chloride (HK) group, with 16 rats in each group. Cardiac arrest (CA) /CPR model was established by transesophageal electrical stimulation to induce ventricular fibrillation. Rats were received equal volume of normal saline and the corresponding dose of potassium chloride via intravenous injection when CPR was initiated at 6 min after CA. The mean arterial pressure (MAP) and the blood potassium concentration were detected after return of spontaneous circulation(ROSC). The neurological deficit scores (NDS), the changes of cell morphology of hippocampal tissue, the content of adenosine-triphosphate, the activity of Na⁺/K⁺-ATP enzymes, the respiratory chain complex (Ⅰ/Ⅱ/Ⅲ/Ⅳ) of the hippocampal tissue at 24 h post ROSC were recorded and observed between different groups. Results Compared with the NS group, the blood potassium was significantly higher in the MK group and the HK group at 1 min and 10 min post ROSC (P<0.05). Compared with the NS group, the MAP after ROSC was not significantly affected, and the NDS was significantly increased at 24 h after ROSC in the MK group (P<0.05). Compared with the NS group, the MAP within 8 min after ROSC was significantly decreased (P<0.05), and the NDS was not significantly improved at 24 h post ROSC in the HK group. Compared with the NS group, the activity of hippocampal respiratory chain complex Ⅲ was increased in the LK group, and the content of ATP was increased (P<0.05). Compared with the NS group, the activity of respiratory chain complex (Ⅰ/Ⅱ/Ⅲ), the content of ATP and the activity of Na⁺/K⁺-ATP enzyme at 24 h post ROSC were increased in the MK group (P<0.05), and hippocampal cell morphology was improved 24 h after ROSC. Compared with the NS group, the activity of respiratory chain complex Ⅲ increased in the HK group (P<0.05). The MK group showed the most obvious improvement in each evaluation index. Conclusion Moderately elevating blood potassium at onset of CPR can improve mitochondrial function and alleviate cerebral ischemia -reperfusion injury in CPR.

Key words: potassium chloride, cardiopulmonary resuscitation, reperfusion injury, mitochondria, electron transport, complex

中图分类号:

R345

图/表 8

参考文献 13

[1]	DIAO M Y, ZHENG J, SHAN Y, et al. Hypothermia prevents hippocampal oxidative stress and apoptosis via the GSK-3β/Nrf2/HO-1 signaling pathway in a rat model of cardiac arrest-induced brain damage[J]. Neurol Res, 2020, 42(9):773-782. doi:10.1080/01616412.2020.1774210.
[2]	句海松, 陈尚恭, 郝建明, 等. 心脏停跳后给高钾对大鼠离体心肌再灌注损伤的保护作用及其机理[J]. 中国病理生理杂志, 1991,(2):162.
	GOU H S, CHEN S G, HAO J M, et al. Protective effect and mechanism of high potassium on isolated myocardial reperfusion injury in rats after cardiac arrest[J]. Chinese Journal of Pathophysiology, 1991,(2):162. doi:10.3321/j.issn:1000-4718.1991.02.059.
[3]	杨叶桂, 李诺, 石佳欣, 等. 提高血钾浓度通过减轻氧化应激改善心肺复苏大鼠脑缺血再灌注损伤[J]. 岭南急诊医学杂志, 2022, 27(3): 205-207,238.
	YANG Y G, LI N, SHI J X, et al. Increasing serum potassium concentrationalleviatescerebral ischemia-reperfusion injury via alleviating oxidative stress in rats during cardiopulmonary resuscitation[J]. Lingnan Journal of Emergency Medicine, 2022, 27(3):205-207,238. doi:10.3969/j.issn.1671-301X.2022.03.001.
[4]	CHEN M H, LIU T W, XIE L, et al. A simpler cardiac arrest model in rats[J]. Am J Emerg Med, 2007, 25(6):623-630. doi:10.1016/j.ajem.2006.11.033.
[5]	YU S P, YEH C H, SENSI S L, et al. Mediation of neuronal apoptosis by enhancement of outward potassium current[J]. Science, 1997, 278(5335):114-117. doi:10.1126/science.278.5335.114.
[6]	MONTAGUE J W, BORTNER C D, HUGHES F M J R, et al. A necessary role for reduced intracellular potassium during the DNA degradation phase of apoptosis[J]. Steroids, 1999, 64(9):563-569. doi:10.1016/s0039-128x(99)00034-3.
[7]	TAN X F, QIN T, LI N, et al. High-potassium preconditioning enhances tolerance to focal cerebral ischemia-reperfusion injury through anti-apoptotic effects in male rats[J]. J Neurosci Res, 2019, 97(10):1253-1265. doi:10.1002/jnr.24483.
[8]	JASTROCH M, DIVAKARUNI A S, MOOKERJEE S, et al. Mitochondrial proton and electron leaks[J]. Essays Biochem, 2010, 47:53-67. doi:10.1042/bse0470053.
[9]	MOROTA S, PIEL S, HANSSON M J. Respiratory uncoupling by increased H⁺ or K⁺ flux is beneficial for heart mitochondrial turnover of reactive oxygen species but not for permeability transition[J]. BMC Cell Biol, 2013, 14:40. doi:10.1186/1471-2121-14-40.
[10]	HAN C K, KUO W W, SHEN C Y, et al. Dilong prevents the high-KCl cardioplegic solution administration-induced apoptosis in H9c2 cardiomyoblast cells mediated by MEK[J]. Am J Chin Med, 2014, 42(6):1507-1519. doi:10.1142/s0192415x14500943.
[11]	NGUYEN THI P A, CHEN M H, LI N, et al. PD98059 protects brain against cells death resulting from ROS/ERK activation in a cardiac arrest rat model[J]. Oxid Med Cell Longev, 2016, 2016:3723762. doi:10.1155/2016/3723762.
[12]	LI N, QIN S, XIE L, et al. Elevated serum potassium concentration alleviates cerebral ischemia-reperfusion injury via mitochondrial preservation[J]. Cell Physiol Biochem, 2018, 48(4):1664-1674. doi:10.1159/000492289.
[13]	TANI M, NEELY J R. Mechanisms of reduced reperfusion injury by low Ca²⁺ and/or high K⁺[J]. Am J Physiol, 1990, 258(4 Pt 2):H1025-1031. doi:10.1152/ajpheart.1990.258.4.H1025.

组别	体质量/g	心率/（次/min）	MAP/mmHg	电刺激时间/s
SH组	222.13±9.51	390.88±16.20	93.19±7.17
NS组	225.13±9.05	393.81±22.98	92.44±7.81	61.75±2.38
LK组	223.38±7.77	384.94±14.22	93.31±6.34	61.44±2.25
MK组	222.75±6.05	389.56±16.86	90.75±5.61	61.88±3.05
HK组	224.31±8.93	394.25±17.94	94.13±7.32	61.13±2.06
F	0.330	0.711	0.546	0.298

组别	体质量/g	心率/（次/min）	MAP/mmHg	电刺激时间/s
SH组	222.13±9.51	390.88±16.20	93.19±7.17
NS组	225.13±9.05	393.81±22.98	92.44±7.81	61.75±2.38
LK组	223.38±7.77	384.94±14.22	93.31±6.34	61.44±2.25
MK组	222.75±6.05	389.56±16.86	90.75±5.61	61.88±3.05
HK组	224.31±8.93	394.25±17.94	94.13±7.32	61.13±2.06
F	0.330	0.711	0.546	0.298

组别	ROSC 只数	ROSC 时间/s	ROSC后24 h 生存只数	ROSC 后24 h NDS/分
SH组	0		16	80.00±0.00
NS组	10	92.70±14.28	9	72.11±1.45^a
LK组	12	83.00±10.97	12	73.58±1.68
MK组	15	82.53±12.87	15	76.40±1.35^bc
HK组	10	98.60±15.47^cd	9	72.67±2.23^d
F		3.927^＊		68.534^＊＊

组别	ROSC 只数	ROSC 时间/s	ROSC后24 h 生存只数	ROSC 后24 h NDS/分
SH组	0		16	80.00±0.00
NS组	10	92.70±14.28	9	72.11±1.45^a
LK组	12	83.00±10.97	12	73.58±1.68
MK组	15	82.53±12.87	15	76.40±1.35^bc
HK组	10	98.60±15.47^cd	9	72.67±2.23^d
F		3.927^＊		68.534^＊＊

组别	n	2 min	4 min	6 min	8 min	10 min	30 min	60 min
SH组	16	87.88±3.84	86.81±3.94	87.06±4.33	87.25±3.73	87.00±4.05	87.56±3.37	87.81±3.80
NS组	9	72.90±2.51^a	74.60±3.03^a	75.70±1.83^a	77.00±2.10^a	77.40±2.95^a	78.50±3.24^a	78.40±3.60^a
LK组	12	78.33±5.21^b	78.83±5.37	79.42±5.52	80.50±4.78	80.58±4.62	80.75±5.03	80.75±5.85
MK组	15	73.60±2.97	73.93±2.52	74.93±2.74	75.93±3.61	77.13±3.87	78.27±4.53	78.40±4.82
HK组	9	58.90±4.46^bcd	61.00±4.57^bcd	62.80±4.76^bcd	66.00±6.68^bcd	71.30±8.54	73.80±7.70^c	75.70±6.89
F		89.356^＊＊	68.531^＊＊	57.534^＊＊	39.473^＊＊	17.440^＊＊	14.489^＊＊	11.805^＊＊

适度提高血钾浓度可改善心肺复苏大鼠脑组织线粒体功能

Moderately elevating blood potassium concentration can improve mitochondrial function of brain tissue in cardiopulmonary resuscitation rats

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组别	CA前	ROSC后1 min	ROSC后10 min
SH组	3.93±0.14	3.92±0.16	3.85±0.15
NS组	3.92±0.22	4.83±0.21^a	4.15±0.22
LK组	3.91±0.23	5.22±0.28	4.34±0.35
MK组	3.84±0.18	5.82±0.35^b	5.15±0.34^bc
HK组	3.84±0.16	6.52±0.39^bc	5.67±0.42^bc
F	0.965	56.277^＊＊	51.072^＊＊

组别	ATP/（μmol/g）	Na⁺/K⁺-ATP酶活性/（U/mg）
SH组	336.31±12.68	26.39±2.69
NS组	290.93±11.96^a	18.93±1.21^a
LK组	310.27±17.48^b	20.40±2.26
MK组	318.10±16.21^b	22.30±2.11^b
HK组	305.89±18.61	20.20±1.12
F	7.988^＊＊	15.213^＊＊

组别	复合体Ⅰ	复合体Ⅱ	复合体Ⅲ	复合体Ⅳ
SH组	5.27±0.31	6.05±0.40	3.43±0.29	3.70±0.36
NS组	4.08±0.38^a	4.29±0.31^a	2.59±0.15^a	3.42±0.31
LK组	4.43±0.33	4.50±0.39	2.93±0.19^b	3.52±0.42
MK组	4.74±0.45^b	5.04±0.23^bc	3.11±0.36^b	3.60±0.66
HK组	4.34±0.53^d	4.42±0.32^d	2.90±0.13^b	3.36±0.38
F	11.933^＊＊	32.680^＊＊	11.747^＊＊	0.677

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