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U50,488H抑制中性粒细胞在大鼠缺血/再灌注心肌中的聚集和TNF-α 生成

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第4期
页码:
491-495
栏目:
基础研究
出版日期:
2010-06-10

文章信息/Info

Title:
U50,488H inhibits ischemia/reperfusion-induced neutrophil accumulation and TNF-α production in rat hearts
作者:
童光1; 魏旭峰1; 顾春虎1; 张权宇2; 李娟2; 易定华1; 裴建明2
第四军医大学：1.西京医院心外科，2.基础部生理教研室，陕西 西安 710032
Author(s):
TONG Guang1;  WEI Xu-feng1;  GU Chun-hu1;  ZHANG Quan-yu2;  LI Juan2;  YI Ding-hua1;  PEI Jian-ming2
1.Department of Cardiovascular Surgery, Xijing Hospital, 2.Department of Physiology, School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
U50; 488H; 缺血/再灌注损伤; 中性粒细胞; 肿瘤坏死因子-α; 大鼠
Keywords:
κ-opioid receptor;  U50; 488H;  ischemia-reperfusion injury;  nitric oxide;  neutrophil;  TNF-α
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的: 观察К-阿片受体激活对大鼠心肌缺血/再灌注（MI/R）局部心肌中性粒细胞聚集的影响及其相关机制。方法: 将60只成年健康SD大鼠随机分为假手术组、缺血/再灌注(I/R)生理盐水组、К-阿片受体激动剂(U50,488H)组、U50,488H+Nor-BNI组、U50,488H+Wortmannin组及U50,488H+L-精氨酸甲酯(L-NAME)组，每组9~10只大鼠。使心肌局部缺血30 min再灌注3 h后处死动物，检测大鼠心梗面积并按相应试剂盒提供方法检测血清肌酸激酶（CK）、心肌中髓过氧化物酶（MPO）活性、一氧化氮（NO）及心肌和血清中肿瘤坏死因子-α（TNF-α）的水平。结果: 与I/R生理盐水组相比较， U50,488H组的心梗面积（P<0.05）、血清CK活性（P<0.05）、心肌MPO（P<0.05）及心肌和血清TNF-α（P<0.05）的水平明显下降，同时心肌中NO（P<0.05）的水平上升；而К-阿片受体的选择性阻断剂(Nor-BNI)、PI3K的选择性抑制剂(Wortmannin)及NO合成酶(NOS)抑制剂(L-NAME)均可消除U50,488H的上述作用（P<0.05）。结论: U50,488H可通过激活К-阿片受体，发挥对心脏的保护作用。U50,488H的保护作用可能与其激活PI3-激酶， 增加心肌中NO的合成，减少中性粒细胞向I/R损伤心肌的聚集和MI/R诱导的TNF-α生成有关。
Abstract:
AIM: To investigate alterations in neutrophil accumulation and TNF-α levels after activation of kappa (κ)-opioid receptor by U50,488H in ischemia/reperfusion-injured rat hearts and the possible mechanism involved. METHODS: Rats were randomly exposed to sham operation, myocardial ischemia/reperfusion (MI/R) alone, MI/R+U50,488H, MI/R+U50,488H+Wortmannin, and MI/R+U50,488H+L-NAME. RESULTS: Compared with those in MI/R group, U50,488H reduced myocardial infarction area, myocardial myeloperoxidase (MPO) level, serum creatinine kinase (CK) level and serum and myocardial TNF-α production. U50,488H also increased the NOx level in myocardium subjected to I/R injury. All the effects of U50,488H were abolished by Nor-BNI, a selective κ-opioid antagonist, by Wortmannin, a specific PI3K inhibitor; and by L-NAME, a nitric oxide synthase (NOS) inhibitor. CONCLUSION: U50,488H is cardioprotective through the activation of κ-opioid receptor. This protective effect may be associated with the increase in NO production caused by activation of PI3K pathway and the inhibition of neutrophil accumulation and TNF-α introduction caused by U50,488H treatment in myocardium subjected to I/R.

参考文献/References

［1］Gross GJ. Role of opioids in acute and delayed preconditioning ［J］. J Mol Cell Cardiol, 2003, 35(7):709-718.

［2］Walker JS. Anti-inflammatory effects of opioids［J］. Adv Exp Med Biol, 2003, 521:148-160.

［3］Meldrum DR, Cleveland JC Jr, Cain BS, et al. Increased myocardial tumor necrosis factor-alpha in a crystalloid-perfused model of cardiac ischemia-reperfusion injury［J］. Ann Thorac Surg, 1998, 65(2):439-443.

［4］Gurevitch J, Frolkis I, Yuhas Y, et al. Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion［J］. J Am Coll Cardio, 1997, 30(6):1554-1561.

［5］Lefer AM, Ma XL, Weyrich A, et al. Endothelial dysfunction and neutrophil adherence as critical events in the development of reperfusion injury［J］. Agents Actions Suppl, 1993, 41:127-135.

［6］Ma XL, Lefer DJ, Lefer AM, et al. Coronary endothelial and cardiac protective effects of a monoclonal antibody to intercellular adhesion molecule-1 in myocardial ischemia and reperfusion［J］. Circulation, 1992, 86(3):937-946.

［7］Chandrasekar B, Smith JB, Freeman GL. Ischemia-reperfusion of rat myocardium activates nuclear factor-KappaB and induces neutrophil infiltration via lipopolysaccharide-induced CXC chemokine［J］. Circulation, 2001, 103(18):2296-2302.

［8］ Li J, Wu F, Zhang H, et al. Insulin inhibits leukocyte-endothelium adherence via an Akt-NO-dependent mechanism in myocardial ischemia/reperfusion［J］. J Mol Cell Cardiol, 2009, 47(4):512-529.

［9］Li J, Zhang H, Wu F, et al. Insulin inhibits tumor necrosis factor-alpha induction in myocardial ischemia/reperfusion: role of Akt and endothelial nitric oxide synthase phosphorylation［J］. Crit Care Med, 2008, 36(5):1551-1558.

［10]Li J, Zhang P, Zhang QY, et al. Effects of U50,488H on hypoxia pulmonary hypertension and its underlying mechanism［J］. Vascul Pharmacol, 2009, 51(2-3):72-77.

备注/Memo

备注/Memo:
收稿日期：2009-12-17.通讯作者：易定华， 主任医师，主要从事冠心病、复杂先心病、心脏移植的研究Email:yidh@fmmu.edu.cn 共同通讯作者：裴建明，教授，主要从事心血管生理学的研究Email:jmpei8@fmmu.edu.cn 作者简介：童光，硕士生Email:sniperparatrooper@yahoo.com
更新日期/Last Update: 2010-05-20