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姜黄素后处理通过JAK2/STAT3信号通路拮抗心肌缺血/再灌注损伤(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2012年第3期
页码:
298-302
栏目:
基础研究
出版日期:
2012-06-25

文章信息/Info

Title:
Protective effect of JAK2/STAT3 signaling pathway in curcumin post-treatment against myocardial ischemia/reperfusion injury in rats
作者:
段维勋1; 杨 阳1; 金振晓1; 赫荣智1; 张建英2; 耿晓东3; 易定华1
(第四军医大学：1.西京医院心血管外科，2.基础部生理学教研室，陕西 西安 710032； 3.北京军区北戴河疗养院医务部医疗科，河北 秦皇岛 066100)
Author(s):
DUAN Wei-xun1;  YANG Yang1;  JIN Zhen-xiao1;  HE Rong-zhi1;  ZHANG Jian-ying2;  GENG Xiao-dong3;  YI Ding-hua1
(1.Department of Cardiovascular Surgery, Xijing Hospital, 2.Department of Physiology, School of Basic Medical Sciences, Fourth Military Medical University, Xi’an 710032, Shaanxi, China; 3.Department of Medical Administration, Beidaihe Sanatorium, Beijing Military Area Command, Qinhuangdao 066100, Hebei, China)
关键词:
姜黄素; 心肌; 缺血/再灌注; JAK2/STAT3信号通路; 大鼠
Keywords:
curcumin;  myocardium;  ischemia reperfusion;  JAK2/STAT3 signaling pathway
分类号:
R284.1
DOI:
-
文献标识码:
A
摘要:
目的:观察姜黄素（curcumin，Cur）后处理对离体心肌缺血/再灌注损伤(ischemia and reperfusion injury，I/RI)的拮抗作用及其可能的机制。方法： 40只SD大鼠随机分为5组(n=8)，即空白对照(Ctl组)、缺血/再灌注组(I/R组)、I/R+姜黄素后处理组(I/R+Cur组)、I/R+姜黄素后处理+AG490组(I/R+Cur+AG组)及AG490组（AG组），AG490为JAK2/STAT3信号通路特异性阻断剂。采用离体大鼠心脏Langendoff逆行灌注模型，缺血60 min，再灌注60 min。分别于缺血前及再灌注后15 min、30 min、45 min和60 min，测定血流动力学各项指标，包括：心率（HR）、左心室发展压（LVDP）、左心室内压力上升的最大速率(+dp/dtmax)、冠脉流量（CF）、计算出心率压力指数（DP，LVDP×HR/1000）。用氯化三苯基四氮唑(TTC)染色法测定各组心肌梗死(MI)的面积，用Western blot检测各组JAK2、磷酸化JAK2(p-JAK2)、STAT3以及磷酸化STAT3(p-STAT3)的表达。结果： 与Ctl组比较，I/R组各时间点的收缩及舒张功能均显著降低(P<0.01)，MI面积显著增加(P<0.01)，磷酸化JAK2和STAT3的表达明显升高(P<0.01)。与I/R组比较，I/R+Cur组各时间点的心肌收缩及舒张功能下降程度明显减轻(P<0.01)，MI的面积明显减少(P<0.01)，p-JAK2和STAT3的表达更高(P<0.01)。与I/R+Cur组相比，I/R+Cur+AG组各时间点的收缩及舒张功能显著降低(P<0.01)，MI的面积显著增加(P<0.01)，p-JAK2和STAT3的表达显著下降(P<0.01)；和Ctl组相比，AG组血流动力学和MI的面积无统计学差异。结论： Cur后处理对I/R大鼠心肌具有保护作用，其作用机制与JAK2/STAT3信号通路的活化有关。
Abstract:
AIM:To investigate the protective effect of post-treatment with curcumin on myocardial ischemia reperfusion in adult Sprague Dawley (SD) rats along with the underlying mechanism. METHODS: The hearts of 40 SD rats were isolated and subjected to Langendorff perfusion. Rats were randomized into five groups (n=8): control group, I/R group, I/R+Cur group, I/R+Cur+AG group and AG group. Myocardial injuries in rats were produced by ischemia for 60 min followed by 60 min reperfusion. HR, LVDP, +dp/dtmax, CF and DP were recorded, respectively, before and 15, 30, 45 and 60 min after reperfusion. Myocardial infarct sizes were observed by TTC test and JAK and STAT3 as well as active phosphorylated forms of JAK2 and STAT3 were detected by Western blotting. RESULTS: In I/R group, systolic and diastolic functions were significantly reduced. Myocardial infarct size was increased and the phosphorylated forms of the JAK2 and STAT3 were significantly higher compared with the control group (P<0.01). In I/R+Cur group, systolic and diastolic functions were improved, myocardial infarct size was significantly smaller, and the phosphorylated forms of JAK2 and STAT3 were significantly higher compared with those in the I/R group (P<0.01). All these parameters in the I/R+Cur+AG group were decreased significantly compared with I/R+Cur group (P<0.01). No significant difference was observed in hemodynamic and myocardial infarct size parameters between control group and AG group. CONCLUSION: Post-treatment with curcumin can significantly reduce myocardial ischemia/reperfusion injury partly via JAK2/STAT3 signaling pathway.

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备注/Memo

备注/Memo:
收稿日期：2011-10-17.基金项目：国家自然科学基金项目资助（81102687）；西京医院学科助推计划项目资助（XJZT09M16和XJZT10M12） 通讯作者：易定华，主任医师，主要从事冠心病外科和瓣膜病外科研究 Email：dinghuayi210@126.com 共同通讯作者：金振晓，副主任医师，主要从事心肌保护研究 Email：jinzx@fmmu.edu.cn 作者简介：段维勋，主治医师 Email：yang200214yy@163.com
更新日期/Last Update: 2012-05-02