中国医科大学学报

中国医科大学学报
  • 中文核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
  • BA、CA收录

中国医科大学学报 ›› 2018, Vol. 47 ›› Issue (12): 1123-1127.doi: 10.12007/j.issn.0258-4646.2018.12.016

• 论著 • 上一篇    下一篇

β受体拮抗剂对脓毒症大鼠心肌细胞线粒体损伤的保护作用

洪澄英, 陈怀生, 曹静, 杜玉洛, 刘雪燕, 李威   

  1. 暨南大学附属第二临床医院, 深圳市人民医院重症医学科, 广东 深圳 518020
  • 收稿日期:2017-10-25 出版日期:2018-12-06 发布日期:2018-12-06
  • 通讯作者: 李威 E-mail:liweiszyy@163.com
  • 作者简介:洪澄英(1979-),女,副主任医师,硕士.
  • 基金资助:
    深圳市科技研发资金知识创新计划(JCY20140416122811971)

Protective Effect of a β-Receptor Antagonist on the Impairment of Cardiocyte Mitochondria in a Rat Sepsis Model

HONG Chengying, CHEN Huaisheng, CAO Jing, DU Yuluo, LIU Xueyan, LI Wei   

  1. Intensive Care Unit, Shenzhen People's Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen 518020, China
  • Received:2017-10-25 Online:2018-12-06 Published:2018-12-06

摘要: 目的 探讨β受体拮抗剂对脓毒症大鼠心肌细胞线粒体功能的影响。方法 取SD大鼠20只,随机分为4组,每组5只。对照组不做处理,剩余3组采用小剂量内毒素持续注射法建立脓毒症大鼠模型,并分为模型组,美托洛尔组和艾司洛尔组。治疗前(0 h)、治疗24 h和48 h后检测各组大鼠心率、平均动脉血压;并于治疗48 h后处死大鼠,取心肌组织切片行病理学检测:HE染色,电子显微镜下观察线粒体;qPCR和Western blotting检测各组线粒体内膜特异的腺甘酸转移酶(ANT)mRNA和蛋白表达水平。结果 内霉素建模后,模型组、美托洛尔组和艾司洛尔组大鼠与对照组比较均出现精神萎靡不振、竖毛、嗜睡、眼鼻渗血、稀便等脓毒症症状,体温和白细胞均显著下降(均P < 0.001),而血清TNF-α及IL-6表达水平均显著升高(均P < 0.05),表明脓毒症大鼠模型建立成功。治疗48 h后,美托洛尔组和艾司洛尔组心率低于模型组,而平均动脉压高于模型组(均P < 0.05)。模型组大鼠心肌细胞排列疏松,电镜下细胞肌纤维断裂,线粒体、肌浆网形态辨认困难,而美托洛尔组和艾司洛尔组大鼠心肌细胞形态接近对照组,电子显微镜下可见心肌细胞肌纤维束排列有序,线粒体、肌浆网形态可见但有部分异常。美托洛尔组和艾司洛尔组ANT mRNA和蛋白表达水平均显著高于模型组(均P < 0.05)。结论 β受体拮抗剂对脓毒症心肌细胞线粒体损伤具有一定保护作用。

关键词: 脓毒症, 心肌损伤, 线粒体, β受体拮抗剂, 大鼠

Abstract: Objective To investigate the protective effect of a β-receptor antagonist on the impairment of cardiocyte mitochondria in a rat sepsis model. Methods Twenty SD rats were randomized into control,model,metoprolol,and esmolol groups. Continuous lipopolysaccharide (LPS) injection was used to establish a rat sepsis models. Heart rate (HR),mean arterial pressure (MAP),and mitochondrial-specific expression of adenosine transferase (ANT) were measured. Mitochondrial morphology was observed by hematoxylin and eosin staining. Results After LPS stimulation,rats in the model,metoprolol,and esmolol groups presented with sepsis symptoms,decreased body temperature and white blood cell counts,and increased serum tumor necrosis factor-α and interleukin-6 expression compared with those in the control group (all P < 0.05). After treatment for 48 h,HR decreased,while MAP increased in metoprolol and esmolol groups relative to those in the model group (all P < 0.05). Rats in the model group showed loosely arranged cardiocytes,and abnormal unrecognized mitochondria and sarcoplasmic pattern under the microscope. In contrast,rats in the metoprolol and esmolol groups showed orderly aligned cardiocytes,and recognizable but still abnormal mitochondria and sarcoplasmic pattern. In addition,ANT mRNA and protein expression were both elevated in the metoprolol and esmolol groups compared to those in the model group (all P < 0.05). Conclusion β-receptor antagonists had a protective effect on the impairment of cardiocyte mitochondria in a rat sepsis model to some extent.

Key words: sepsis, myocardial injury, mitochondria, β-receptor antagonist, rat

中图分类号: 

  • R541.9
[1] VAN DER POLL T,VAN DE VEERDONK FL,SCICLUNA BP,et al. The immunopathology of sepsis and potential therapeutic targets[J]. Nat Rev Immunol,2017,17(7):407-420. DOI:10.1038/nri.2017.36.
[2] POLAT G,UGAN RA,CADIRCI E,et al. Sepsis and septic shock:current treatment strategies and new approaches[J]. Eurasian J Med,2017,49(1):53-58. DOI:10.5152/eurasianjmed.2017.17062.
[3] FATTAHI F,WARD PA. Complement and sepsis-induced heart dysfunction[J]. Mol Immunol,2017,84:57-64. DOI:10.1016/j.molimm.2016.11.012.
[4] CELES MR,PRADO CM,ROSSI MA. Sepsis:going to the heart of the matter[J]. Pathobiology,2013,80(2):70-86. DOI:10.1159/000341640.
[5] RUDIGER A,SINGER M. The heart in sepsis:from basic mechanisms to clinical management[J]. Curr Vascular Pharmacol,2013,11(2):187-195. DOI:10.2174/1570161111311020008.
[6] ACUNA-CASTROVIEJO D,RAHIM I,ACUNA-FERNANDEZ C,et al. Melatonin,clock genes and mitochondria in sepsis[J]. Cell Mol Life Sci,2017,74(21):3965-3987. DOI:10.1007/s00018-017-2610-1.
[7] SANFILIPPO F,SANTONOCITO C,MORELLI A,et al. Beta-blocker use in severe sepsis and septic shock:a systematic review[J]. Cur Med Res Opinion,2015,31(10):1817-1825. DOI:10.1185/03007995.2015.1062357.
[8] BALIK M,RULISEK J,LEDEN P,et al. Concomitant use of beta-1 adrenoreceptor blocker and norepinephrine in patients with septic shock[J]. Wiener klin Wochenschr,2012,124(15/16):552-556. DOI:10.1007/s00508-012-0209-y.
[9] SINGER KE,COLLINS CE,FLAHIVE JM,et al. Outpatient beta-blockers and survival from sepsis:results from a national cohort of medicare beneficiaries[J]. Am J Surg,2017,214(4):577-582. DOI:10.1016/j.amjsurg.2017.06.007.
[10] 秦延军,于悦卿,闫雁,等. 艾司洛尔对早期脓毒症大鼠炎症因子及心功能的影响[J]. 中国现代医学杂志,2014,24(1):13-19. DOI:10.3969/j.issn.1005-8982.2014.01.004.
[11] 温妙云,郑侠,邓医宇,等. 内毒素诱导大鼠建立脓毒症脑损伤模型[J]. 广东医学,2014,35(2):198-200. DOI:10.13820/j.cnki.gdyx.2014.02.011.
[12] 李志强,张印纲,程爱斌,等. 美托洛尔对脓毒症大鼠心肌细胞凋亡的影响[J]. 实用医学杂志,2011,27(3):399-402. DOI:10.3969/j.issn.1006-5725.2011.03.015.
[13] 张璐瑶,聂垚,柯路,等. 艾司洛尔对脓毒症大鼠肠黏膜屏障的影响[J]. 肠外与肠内营养,2014,21(5):305-308. DOI:10.16151/j.1007-810x.2014.05.036.
[14] AVLAS O,FALLACH R,SHAINBERG A,et al. Toll-like receptor 4 stimulation initiates an inflammatory response that decreases cardiomyocyte contractility[J]. Antioxidants Redox Signal,2011,15(7):1895-1909. DOI:10.1089/ars.2010.3728.
[15] PARACHA RZ,AHMAD J,ALI A,et al. Formal modelling of toll like receptor 4 and JAK/STAT signalling pathways:insight into the roles of SOCS-1,interferon-beta and proinflammatory cytokines in sepsis[J]. PLoS One,2014,9(9):e108466. DOI:10.1371/journal.pone.0108466.
[16] BAUERFELD CP,RASTOGI R,PIROCKINAITE G,et al. TLR4-mediated AKT activation is MyD88/TRIF dependent and critical for induction of oxidative phosphorylation and mitochondrial transcription factor A in murine macrophages[J]. J Immunol,2012,188(6):2847-2857. DOI:10.4049/jimmunol.1102157.
[17] DADA LA,SZNAJDER JI. Mitochondrial Ca (2) + and ROS take center stage to orchestrate TNF-alpha-mediated inflammatory responses[J]. J Clin Invest,2011,121(5):1683-1685. DOI:10.1172/JCI57748.
[18] CHAGNON F,METZ CN,BUCALA R,et al. Endotoxin-induced myocardial dysfunction:effects of macrophage migration inhibitory factor neutralization[J]. Circulation Res,2005,96(10):1095-1102. DOI:10.1161/01.RES.0000168327.22888.4d.
[19] CHACKO CJ,GOPAL S. Systematic review of use of beta-blockers in sepsis[J]. J Anaesthesiol Clin Pharmacol,2015,31(4):460-465. DOI:10.4103/0970-9185.169063.
[20] GOMEZ A,SANCHEZ-ROMAN I,GOMEZ J,et al. Lifelong treatment with atenolol decreases membrane fatty acid unsaturation and oxidative stress in heart and skeletal muscle mitochondria and improves immunity and behavior,without changing mice longevity[J]. Aging Cell,2014,13(3):551-560. DOI:10.1111/acel.12205.
[21] SANCHEZ-ROMAN I,GOMEZ A,NAUDI A,et al. Independent and additive effects of atenolol and methionine restriction on lowering rat heart mitochondria oxidative stress[J]. J Bioenergetics Biomembranes,2014,46(3):159-172. DOI:10.1007/s10863-013-9535-7.
[1] 吴越, 周祖华, 闻庆平, 苗壮. 葛根素对大鼠背根神经节神经病理性疼痛的镇痛作用[J]. 中国医科大学学报, 2018, 47(9): 803-806.
[2] 刘畅, 柯艳, 赵丽, 崇巍. 急性消化道出血患者心肌损伤的危险因素分析[J]. 中国医科大学学报, 2018, 47(9): 834-837.
[3] 解丽丽, 吕洪涛, 许瑞雪. 磷酸化P38在神经病理性疼痛大鼠背根神经节中的作用机制[J]. 中国医科大学学报, 2018, 47(4): 308-311.
[4] 李晓彤, 秦宇, 赵江月, 张劲松. 线粒体功能障碍与年龄相关性眼部疾病的关系[J]. 中国医科大学学报, 2018, 47(4): 358-363.
[5] 邢海会, 丁晓慧, 解辉, 王忠华, 谢菊华, 陈丰洋, 罗崟洲, 周胜男. Toll样受体4对大鼠脑缺血再灌注损伤的作用[J]. 中国医科大学学报, 2018, 47(3): 206-211.
[6] 张雷, 邢静, 李润玖. 转化生长因子β1对脓毒症大鼠模型免疫功能的影响[J]. 中国医科大学学报, 2018, 47(12): 1111-1115.
[7] 姜晓晓, 周祖华, 常栋, 齐中华. 白藜芦醇对急性心肌梗死大鼠心脏神经重塑的影响及其机制[J]. 中国医科大学学报, 2018, 47(12): 1077-1080.
[8] 曲慧玲, 赵传胜. 强制性运动疗法结合抗抑郁治疗对脑梗死大鼠神经功能的影响[J]. 中国医科大学学报, 2018, 47(12): 1085-1088.
[9] 刘洪祥, 赵彦楠, 霍佳宁, 李达, 马晓欣. 脱氢表雄酮联合高脂饮食诱导大鼠多囊卵巢综合征模型的研究[J]. 中国医科大学学报, 2018, 47(11): 961-963,974.
[10] 徐春卓, 辛颖. 宫内发育迟缓对大鼠胰腺中Ngn3表达及内分泌细胞发育的影响[J]. 中国医科大学学报, 2018, 47(10): 891-894,899.
[11] 赵彦楠,刘洪祥,马晓欣. 晚期糖基化终产物受体在多囊卵巢综合征大鼠模型中的表达[J]. 中国医科大学学报, 2017, 46(9): 769-772.
[12] 张忠霞,马晓伟,王彦永,邱会卿,王铭维. 雷帕霉素对老龄帕金森病模型小鼠线粒体损伤的改善作用[J]. 中国医科大学学报, 2017, 46(9): 783-786.
[13] 白冰 ,宋宏伟 ,刘志. CURB-65 改良评分评估脓毒症预后的研究[J]. 中国医科大学学报, 2017, 46(8): 734-738.
[14] 刘晓颖 ,姚俊洁 ,刘文. 白藜芦醇对链脲霉素诱导的糖尿病大鼠神经病理性疼痛的作用[J]. 中国医科大学学报, 2017, 46(7): 591-594.
[15] 李思琦 ,张哲 ,杨关林 ,宋囡 ,闵冬雨 ,王凤荣. 益气健脾方对脾气虚证模型大鼠心肌细胞线粒体呼吸链酶 复合物活性的影响[J]. 中国医科大学学报, 2017, 46(6): 515-518.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 尚海,郝志强,傅熙博,华向东,马作红,艾福录,冯照强,王坤,李文心,李博. 中介素通过经典Wnt信号途径促进肝癌细胞增殖[J]. 中国医科大学学报, 2014, 43(7): 631 -634 .
[2] 滕浩, 薛一雪, 王萍, 刘云会. miR-194对人脑胶质瘤U87细胞恶性生物学行为的影响[J]. 中国医科大学学报, 2018, 47(8): 673 -677 .
[3] 盖晴, 冷昶木, 丛树艳. 颅神经受累的吉兰-巴雷谱系疾病35例临床分析[J]. 中国医科大学学报, 2018, 47(9): 769 -772 .
[4] 杜国强, 王立银, 王晓凤, 李君, 张明明, 王瑾. APE1通过NF-κB通路调节PD-L1在喉鳞状细胞癌中的表达[J]. 中国医科大学学报, 2018, 47(10): 865 -870 .
[5] 李羽思, 陈旭. 外泌体调控受体细胞DNA甲基化的研究进展[J]. 中国医科大学学报, 2018, 47(12): 1133 -1136 .
[6] 吴鑫, 石晶, 李智, 李贺明, 曲秀娟, 刘云鹏, 张凌云. 中国东北地区人群饮用绿茶与结直肠癌发病关系的病例对照研究[J]. 中国医科大学学报, 2018, 47(12): 1057 -1062 .
[7] 赵滢, 王晓非. 1 757例住院类风湿关节炎患者临床特点分析[J]. 中国医科大学学报, 2018, 47(12): 1107 -1110,1115 .
[8] 叶茂, 张晓春, 张波. 护理预警体系在院内静脉血栓栓塞症防治中的构建与效果评价[J]. 中国医科大学学报, 2018, 47(12): 1140 -1143 .
[9] 窦磊, 庞晓燕, 李奇, 尚海, 张颐. 去酰基化ghrelin抑制上皮性卵巢癌细胞的增殖[J]. 中国医科大学学报, 2018, 47(12): 1102 -1106 .
[10] 贡鸣, 何天宇, 裘敬平, 李光. 6种常见肿瘤患者初治时外周血T淋巴细胞亚群数量及临床特征[J]. 中国医科大学学报, 2018, 47(12): 1119 -1122 .

中国医科大学学报版权所有©2018

未经允许,严禁擅自转载本站图文资料

地址:中国 沈阳市沈北新区蒲河路77号 110122

辽ICP备05014850

JOURNAL OF CHINA MEDICAL UNIVERSITY

ADDRESS: NO.77 PUHE ROAD

SHENYANG NORTH NEW AREA, SHENYANG

LIAONING PROVINCE, P.R. CHINA