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|本期目录/Table of Contents|

RIP3-CaMKII通路激活程序性坏死在糖尿病心肌缺血/再灌注损伤中的作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2018年第2期
页码:
125-129
栏目:
基础研究
出版日期:
2018-02-15

文章信息/Info

Title:
RIP3-CaMKII pathway is involved in activating necroptosis in diabetic myocardial ischemia/reperfusion injury
作者:
薛 涵1; 李 晨2; 杨 铮2; 石曌玲1; 刘曼玲2; 殷 玥1; 2; 马 恒1; 2
（第四军医大学基础部：1.生理学教研室，2.病理生理学教研室，陕西 西安 710032）
Author(s):
XUE Han1;  LI Chen2;  YANG Zheng2;  SHI Zhao-ling1;  LIU Man-ling2;  YIN Yue1; 2;  MA Heng1; 2
(1.Department of Physiology, 2.Department of Pathophysiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
糖尿病; 心肌缺血/再灌注; 程序性坏死; RIP3; CaMKII
Keywords:
diabetes;  myocardial ischemia reperfusion;  necroptosis;  RIP3;  CaMKII
分类号:
R331.3
DOI:
-
文献标识码:
A
摘要:
目的 本研究旨在探讨受体相互作用蛋白(RIP)3-钙离子/钙调蛋白依赖蛋白激酶(CaMK)II通路激活的程序性坏死(necroptosis)在糖尿病心肌缺血/再灌注(I/R)损伤中的作用。方法 成年(3~4月龄)雄性C57BL/6小鼠70只，随机分为正常组（n=30）与STZ诱导的糖尿病组（n=40）。随后采用小鼠急性心肌I/R在体模型(缺血30 min再灌注4 h)。再灌注后取心肌组织，一部分应用Western blot法检测RIP3-CaMKII信号的表达及修饰变化，另一部分做冰冻切片组织免疫荧光，通过伊文氏蓝阳性区域的面积占比反映程序性坏死的程度。结果 与正常组相比，糖尿病组小鼠I/R后心肌程序性坏死程度显著升高（P<0.05）；在糖尿病I/R心肌中RIP3表达水平和磷酸化CaMKII水平较正常组I/R心肌均显著升高（P<0.05）。对糖尿病小鼠再灌注前给予CaMKII抑制剂KN-93处理可以显著降低糖尿病心肌I/R后的程序性坏死比例（P<0.05）。结论 本研究证实在糖尿病心肌I/R损伤中程序性坏死显著增加，提示RIP3-CaMKII信号增强引发心肌程序性坏死在糖尿病心肌缺血易损中起重要作用。
Abstract:
AIM To investigate the role of necroptosis activated by RIP3-CaMKII pathway under conditions of diabetic myocardial ischemia/reperfusion. METHODS Male C57BL/6 mice (aged 3-4 months) were randomized into diabetes and normal control groups. For the diabetes group, a model of type 1 diabetes mellitus was employed. Mice were subjected to a myocardial I/R model utilizing anterior descending artery ligation for 30 minutes followed by 4-hour reperfusion. Myocardial tissue was excised after reperfusion. Western blot was used to detect RIP3 and phospho-CaMKII expression and cryosection and immunofluorescence were used to evaluate necroptosis by Evans-blue dye positive area percentage. RESULTS Compared with the normal I/R group, the diabetic I/R group showed enhanced necroptosis indicated by a higher EBD-positive area percentage (P<0.05) and increased expression of RIP3 and phospho-CaMKII (P<0.05). KN-93, an inhibitor of CaMKII, significantly reduced necroptosis in the diabetic I/R group (P<0.05). CONCLUSION Necroptosis is enhanced in diabetic myocardial I/R injury, implying that enhanced the RIP3-CaMKII pathway, which activates myocardial necroptosis, plays an important role in diabetic myocardial I/R.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2017-10-16.基金项目：国家自然科学基金项目资助（81322004，31671424）；陕西省社发攻关项目资助（2011KJXX66，2015KW-050） 通讯作者：马恒，副教授，主要从事心肌内源性保护机制研究 Email:hengma@fmmu.edu.cn 作者简介：薛涵，硕士生 Email：362703437@qq.com
更新日期/Last Update: 1900-01-01