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[1]吕磊,李瑶,王永园,等.尼可地尔对力竭运动大鼠心肌损伤的保护作用研究[J].医学研究与战创伤救治(原医学研究生学报),2021,23(03):230-234.[doi:10.3969/j.issn.1672-271X.2021.03.002]
　LV Lei,LI Yao,WANG Yong-yuan,et al.Protective effect of nicorandil against exhausted exercise inducedmyocardial injury in rats[J].JOURNAL OF MEDICALRESEARCH —COMBAT TRAUMA CARE,2021,23(03):230-234.[doi:10.3969/j.issn.1672-271X.2021.03.002]
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尼可地尔对力竭运动大鼠心肌损伤的保护作用研究()
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《医学研究与战创伤救治》（原医学研究生学报）[ISSN:1672-271X/CN:32-1713/R]

卷:
第23卷
期数:
2021年03期
页码:
230-234
栏目:
出版日期:
2021-06-20

文章信息/Info

Title:
Protective effect of nicorandil against exhausted exercise inducedmyocardial injury in rats
作者:
吕磊; 李瑶; 王永园; 金涛; 钟勇
作者单位：210002南京，东部战区总医院（原南京军区南京总医院）干部心内科（吕磊、李瑶、王永园），健康医学科（金涛、钟勇）
Author(s):
LV Lei; LI Yao; WANG Yong-yuan; JIN Tao; ZHONG Yong
（1.Department of Geriatric Cardiology, 2.Health Medicine Centre, General Hospital of Eastern Theater Command, PLA, Nanjing 210002，Jiangsu, China）
关键词:
力竭运动; 尼可地尔; 心肌损伤; 超微结构; 应激
Keywords:
exhaustive exercise;  nicorandil;  myocardial injury;  ultrastructure;  stress
分类号:
R541
DOI:
10.3969/j.issn.1672-271X.2021.03.002
文献标志码:
A
摘要:
目的探讨不同剂量尼可地尔对一次性力竭运动大鼠心肌损伤的影响。方法雄性SD大鼠35只随机分为5组：对照组、力竭组、尼可地尔低剂量组[1 mg/(kg·d)]、尼可地尔中剂量组[3 mg/(kg·d)]、尼可地尔高剂量组[9 mg/(kg·d)]。不同剂量尼可地尔组给予尼可地尔灌胃4周，对照组和力竭组予以等渗盐水3 mg/(kg·d)灌胃4周。除对照组外，其余各组预处理后均行一次性力竭运动。电镜下观察组织病理学改变，检测血清天门冬氨酸氨基转移酶（AST）、乳酸脱氢酶（LDH）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）和心肌肌钙蛋白I（cTnI）活性，血浆去甲肾上腺素（NE）、肾上腺素（E）、多巴胺（DA）等儿茶酚胺（CA）水平，血清丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性以及心肌组织ATP含量。结果电镜下力竭组大鼠心肌线粒体嵴断裂，空泡变性，部分重度水肿，肌节紊乱，尼可地尔组线粒体损伤程度较轻，尼可地尔中剂量和高剂量组改善最为明显。力竭组血浆CA水平分别为NE（4185.28±683.48）pg/mL，E（4119.34±766.76）pg/mL，DA（814.03±411.02）pg/mL，血清cTnI（18.65±4.41）ng/mL，较对照组[分别为NE（739.50±336.68）pg/mL，E（2225.81±442.77）pg/mL，DA（95.11±23.44）pg/mL，cTnI（0.65±0.25）ng/mL]明显升高（P<0.05）。力竭组较对照组心肌组织ATP含量[（283.19±128.35） vs （509.21±76.18）μmol/g]明显降低，血浆SOD活性[（402.88±53.94） vs （528.81±76.98）U/mL]降低，MDA水平[（11.34±2.44） vs （4.68±0.41）nmol/mL ]明显升高（P＜0.05）。尼可地尔低、中、高剂量组血清cTnI均低于力竭组（P＜0.05）。尼可地尔低、中、高剂量组NE水平均低于力竭组，尼可地尔高剂量组E和DA水平低于力竭组（P<0.05）。尼可地尔中、高剂量组ATP含量[分别为（310.71±74.12）μmol/g 和（312.01±101.07）μmol/g] 高于力竭组，但仅尼可地尔中剂量组差异有统计学意义（P＜0.05）。结论 力竭运动导致心肌超微结构损伤，但尼可地尔能减轻心肌损伤，其机制可能与降低氧化应激损伤和儿茶酚胺水平，提高心肌组织ATP含量有关。结论力竭运动导致心肌超微结构损伤，但尼可地尔能减轻心肌损伤，其机制可能与降低氧化应激损伤和儿茶酚胺水平，提高心肌组织ATP含量有关。
Abstract:
ObjectiveTo investigate the effects of different doses of nicorandil on myocardial injury in rats after exhaustive exercise.MethodsThirty-five male Sprague Dawley rats were randomly divided into 5 groups: control group, exhaustive exercise group, low-dose nicorandil group [1 mg/(kg·d)], medium-dose nicorandil group [3 mg/(kg·d)], high-dose nicorandil group [9mg/(kg·d)]. Nicorandil groups were given different doses of nicorandil while control group and exhaustive exercise group were given saline [3 mg/(kg·d)] by gavage for 4 weeks. Except for the control group, the other groups were given one-time exhaustive exercise after pretreatment. Histopathological changes were observed under electron microscope. The activities of serum aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and cardiac troponin I (cTnI), plasma catecholamine (CA) levels such as adrenaline (E), norepinephrine (NE), dopamine (DA), the content of serum malondialdehyde (MDA), the activity of superoxide dismutase (SOD), and the content of ATP in myocardial tissue were detected.ResultsUnder an electron microscope, mitochondrial cristae were broken. Vacuolar degeneration, some severe edema and sarcomere disorder were found in exhausted group. The damage degree of mitochondria in nicorandil group was milder, and the improvement was most obvious in medium-dose nicorandil group and high-dose nicorandil group. The levels of plasma CA and cTnI in exhaustive exercise group were significantly higher than those in control group, NE (4185.28± 683.48) vs (739.50±336.68) pg/mL, E (4119.34±766.76) vs (2225.81±442.77) pg/mL, DA (814.03±411.02) vs (95.11±23.44) pg/mL, cTnI(18.65±4.41）vs (0.65±0.25) ng/mL, respectively (P<0.05). Compared with control group, the content of ATP in exhaustive exercise group was significantly decreased [(283.19±128.35) vs (509.21±76.18) μ mol/g], the activity of SOD was decreased [(402.88±53.94) vs (528.81±76.98) U/mL], and the level of MDA was significantly increased [(11.34±2.44) vs (4.68±0.41) nmol/mL] (all P<0.05). The serum cTnI of low, medium and high dose nicorandil groups were (10.86±3.61) ng/mL, (9.57±2.78) ng/mL and (10.15±2.27) ng/mL respectively, which were significantly lower than those of exhaustive exercise group (all P<0.05). The levels of CA in high-dose nicorandil group were significantly lower than those in exhaustive exercise group [NE (1856.81±964.98) pg/mL, E (3384.27±956.33) pg/mL and DA (421.47±194.43) pg/mL, all P<0.05]. The ATP contents of medium-dose and high-dose nicorandil group were (310.71±74.12) μ mol/g and (312.01±101.07) μ mol/g respectively, which were higher than that of exhaustive exercise group. The difference was significant in medium-dose nicorandil group (P<0.05).ConclusionExhaustive exercise leads to myocardial ultrastructural damage, increase of myocardial enzymes and CA levels, and decrease of myocardial ATP content. Nicorandil can alleviate myocardial injury, which may be related to the decrease of oxidative stress injury and catecholamine level, and increase of myocardial ATP content.

参考文献/References:

[1]公雪，李晓燕. 力竭运动对心肌组织结构及功能影响的研究进展[J]. 心血管病学进展，2016, 37(4):435-440.
[2]Tarkin JM, Kaski JC. Vasodilator therapy: nitrates and nicorandil[J]. Cardiovasc Drugs Ther,2016,30(4):367-378.
[3]王志清，陈梅贤，刘东林，等. 预防性冠状动脉内注射尼可地尔对急性ST段抬高型心肌梗死介入治疗后心肌血流灌注及预后的影响[J].中华心血管病杂志, 2017,45(1):26-33.
[4]Wang S, Fan Y, Feng X, et al. Nicorandil alleviates myocardial injury and post-infarction cardiac remodeling by inhibiting Mst1[J]. Biochem Biophys Res Commun, 2018,495(1):292-299.
[5]Bedford TG, Tipton CM, Wilson NC, et al. Maximum oxygen consumption of rats and its changes with various experimental procedures[J]. J Appl Physiol Respir Environ Exerc Physiol, 1979,47(6):1278-1283.
[6]马宏，田攀，李俊峡，等.力竭运动和运动预适应对大鼠心脏跨室壁复极离散度和缝隙连接蛋白43影响的研究[J].中国循证心血管医学杂志，2018,10(3):292-296.
[7]Oláh A, Németh BT, Mátyás C, et al. Cardiac effects of acute exhaustive exercise in a ratmodel[J]. Int J Cardiol,2015,182(5):258-266.
[8]程训民，江时森. 心血管病新的治疗靶点——线粒体通透转运孔开放[J].医学研究生学报，2011, 24(10):1103-1107.
[9]Kuznetsov AV, Javadov S, Margreiter R, et al. The role of mitochondria in the mechanisms of cardiac ischemia-reperfusioninjury[J]. Antioxidants (Basel), 2019,8(10):454.
[10]吴金斌，邹德学，周逵，等. 高敏肌钙蛋白T和普通肌钙蛋白I在急性心肌梗死早期诊断中的临床应用价值[J]. 国际检验医学杂志，2016,37(13):1799-1803.
[11]双田，丁雪燕，马丽萍，等. 急性心肌梗死患者血清肌钙蛋白I抗体检测的临床意义[J]. 东南国防医药，2013,15(1):14-17.
[12]方雯，李泽，刘晓华，等. 一次性力竭运动对大鼠PHB1表达及线粒体功能的影响[J].中国应用生理学杂志，2017,33(6):544-549.
[13]Cadenas S. Mitochondrial uncoupling, ROS generation andcardioprotection[J]. Biochim Biophys Acta Bioenerg, 2018, 1859(9):940-950.
[14]Suzuki K, Tominaga T, Ruhee RT,et al. Characterization and modulation of systemic inflammatory response to exhaustive exercise in relation to oxidative stress[J]. Antioxidants (Basel), 2020,9(5):401-420.
[15]Ono H, Osanai T, Ishizaka H, et al. Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation[J]. Am Heart J, 2004,148(4):E15.
[16]李晓霞，杨涛，陈鲁沂，等. 有氧运动对心力衰竭大鼠循环儿茶酚胺的影响及机制[J]. 北京体育大学学报，2018,41(11):69-73.
[17]Zouhal H, Jacob C, Delamarche P, et al. Catecholamines and the effects of exercise, training and gender[J]. Sports Med, 2008, 38(5):401-423.

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备注/Memo

备注/Memo:
基金项目：军委后勤保障部卫生局保健专项课题（18BJZ13）；中国博士后科学基金（2018M633765）
更新日期/Last Update: 2021-06-17