5-HT2ARB对急性脑损伤致心肌损害及内源性去甲肾上腺素和5-羟色胺的影响

首都医科大学学报 ›› 2010, Vol. 31 ›› Issue (2): 222-227.

5-HT_2ARB对急性脑损伤致心肌损害及内源性去甲肾上腺素和5-羟色胺的影响

郭彩霞¹, 张立克², 芦玲巧², 孙异临³, 杜凤和^1*

1. 首都医科大学附属北京天坛医院心内科;2. 首都医科大学基础医学院病理生理学教研室;3. 首都医科大学附属北京天坛医院电镜室

收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2010-04-21 发布日期:2010-04-21
通讯作者: 杜凤和

Effect of 5-HT2ARB on the Myocardial Damage Caused by Acute Brain Injury and on Endogenous Norepinephrine and 5-hydroxytryptamine

GUO Cai-xia¹, ZHANG Li-ke², LU Ling-qiao², SUN Yi-lin³, DU Feng-he^1*

1. Department of Cardiology Medicine, Beijing Tiantan Hospital, Capital Medical University; 2. Department of Pathophysiology, School of Basic Medical Science, Capital Medical University; 3. Department of Electron Microscope, Beijing Tiantan Hospital, Capital Medical University

Received:1900-01-01 Revised:1900-01-01 Online:2010-04-21 Published:2010-04-21
Contact: DU Feng-he

摘要/Abstract

摘要： 目的通过了解5-羟色胺2A受体阻断剂（5-hydroxytryptamine 2A receptor blocker，5-HT_2ARB）对急性脑损伤致心肌损害的作用及内源性去甲肾上腺素（noradrenaline，NE）和5-羟色胺（5-hydroxytryptamine，5-HT）的影响，探讨NE、5-HT及其5-HT_2AR在急性脑损伤致心肌损害中的作用。揭示急性脑损伤致心肌损害的本质并为临床防治工作提供实验依据。方法采用急性脑损伤动物模型，以心电图、心功能、肌酸激酶-MB同工酶（creatine kinase MB，CK-MB）含量、心肌HE染色及超微结构改变判断心肌损害程度。采用HPLC-ECD测定血浆及心肌组织NE和5-HT水平。采用RT-PCR和real-time RT-PCR方法测定5-HT_2AR。将32只大鼠采用数字表法随机分为正常组、假手术组、急性脑损伤组和5-HT_2AR阻断剂组，每组8只。急性脑损伤后24 h观察大鼠各指标的变化。结果急性脑损伤致心肌损害表现为心电异常增多（P<0.05）；心室收缩舒张功能降低，包括左心室内压上升和下降的最大变化率（±dp/dtmax）和左室发展压（left ventricular developed pressure，LVDP）显著下降（P<0.05），左室舒张末压（left ventricular diastolic end pressure，LVDEP）升高（P<0.05）；CK-MB含量显著增加（P<0.05）；HE染色和超微结构可见心肌灶状变性、坏死及出血等。血浆和心肌组织NE以及血浆5-HT水平显著升高（P<0.05）。应用5-HT_2AR阻断剂后急性脑损伤所致心肌损害的指标明显改善，可降低心肌NE的含量（P<0.05）。结论急性脑损伤可导致心肌损害的发生，可能通过增加内源性5-HT而激活5-HT_2AR引起心肌损害。5-HT_2AR阻断剂可改善急性脑损伤致心肌损害的发生。

关键词: 急性脑损伤, 心肌损害, 5-HT_2ARB, 去甲肾上腺素, 5-羟色胺

Abstract: Objective To understand effects of norepinephrine(NE), 5-hydroxytryptamine(5-HT) and 5-HT_2AR on myocardial damage occurred after acute brain injury(MDABI) through studying role of 5-HT_2ARB in the MDABI and its effect on endogenous NE and 5-HT and to provide further insights into the relationship between the brain and the heart, and the prevention and treatment of MDABI. Methods A rat model of acute brain injury(ABI) was established. ECG, cardiac function(CF), creatine kinase MB(CK-MB) in serum and morphologic changes in myocardium were measured to indicate the degree of myocardial damage. NE and 5-HT in plasma and myocardium were detected by high performance liquid phase chromatography with electrochemical detection(HPLC-ECD). Expression of 5-HT_2AR was determined by RT-PCR and real-time RT-PCR. There were four groups in the experiment including normal, sham, ABI and 5-HT_2ARB group，with 8 rats in each group. Indicators were observed 24 hours after ABI. Results The cardiac abnormalities after acute brain injury included abnormal ECG increased(P<0.05); ventricular systolic and diastolic dysfunction included ±dp/dtmax and left ventricular developed pressure(LVDP) decreased(P<0.05), left ventricular diastolic end pressure(LVDEP) increased(P<0.05); CK-MB increased(P<0.05). Degeneration, necrosis and hemorrhage of myocardium were observed under light and electronic microscope. NE in plasma and myocardium and plasma 5-HT increased significantly(P<0.05). 5-HT_2ARB was beneficial in reducing degree of MDABI and could reduce myocardial NE(P<0.05). Conclusion ABI can lead to myocardial damage. It maybe happen through increasing 5-HT to activate 5-HT_2AR. 5-HT_2ARB can reduce the MDABI.

Key words: acute brain injury, myocardial damage, 5-HT_2ARB, noradrenaline, 5-hydroxytryptamine

中图分类号:

R 54

郭彩霞;张立克;芦玲巧;孙异临;杜凤和. 5-HT_2ARB对急性脑损伤致心肌损害及内源性去甲肾上腺素和5-羟色胺的影响[J]. 首都医科大学学报, 2010, 31(2): 222-227.

GUO Cai-xia;ZHANG Li-ke;LU Ling-qiao;SUN Yi-lin;DU Feng-he. Effect of 5-HT2ARB on the Myocardial Damage Caused by Acute Brain Injury and on Endogenous Norepinephrine and 5-hydroxytryptamine[J]. Journal of Capital Medical University, 2010, 31(2): 222-227.

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