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Rho激酶在急性心肌梗死大鼠中的表达及其对心肌细胞凋亡的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2011年第1期
页码:
16-19,26
栏目:
基础研究
出版日期:
2010-10-27

文章信息/Info

Title:
Expression of Rho-kinase in rats with acute myocardial infarction and its relationship to apoptosis
作者:
潘娜娜1; 谭丽娟1; 马建英1; 孙志萍1; 于希娟2
1.青岛大学医学院附属医院心内科，山东 青岛 266061；2.即墨市田横镇计生办，山东 即墨 266219
Author(s):
PAN Na-na1;  TAN Li-juan1;  MA Jian-ying1;  SUN Zhi-ping1;  YU Xi-juan2
1.Department of Cardiology, Affiliated Hospital, Medical College, Qingdao University, Qingdao 266000, Shandong, China; 2.Family Planning Office of Tian Heng Town, Jimo 266219, Shandong, China
关键词:
心肌梗死; Rho激酶; 细胞凋亡; 大鼠
Keywords:
myocardial infarction;  fasudil;  cell apoptosis
分类号:
R542.22
DOI:
-
文献标识码:
A
摘要:
目的: 分析心肌梗死(MI)后大鼠心肌组织中Rho激酶表达的变化，探讨Rho激酶信号通路与心肌细胞凋亡的关系及其选择性抑制剂法舒地尔对MI后心肌的保护作用。 方法： 选取雄性Wistar大鼠，结扎其左前降支建立急性心肌梗死(AMI)模型。将术后24 h存活的24只大鼠随机分为治疗组（n=12）和AMI组（n=12），另随机选取10只大鼠作为假手术组，只在其左前降支下穿线不结扎。治疗组腹腔注射法舒地尔5 mg/kg，每日两次；AMI组和假手术组给予等量的生理盐水。4周后，用Evens蓝及四唑氮蓝试验(NBT)双染确定缺血及梗死面积；用RT-PCR法测定Rho激酶mRNA的表达；DNA片段分析观察心肌细胞凋亡的情况；用免疫组化染色法测定凋亡相关蛋白bcl-2及bax表达的变化。结果： 与AMI组相比，治疗组的梗死面积显著减小(P<0.05)。AMI大鼠缺血心肌组织中DNA片段分析显示，有DNA梯状条带(ladder)形成，假手术组大鼠却没有。AMI组大鼠中Rho激酶mRNA及凋亡相关蛋白bax的表达明显增加(P<0.01，P<0.01)；bcl-2的表达明显减少(P<0.01)。以法舒地尔治疗4周后，Rho激酶mRNA及bax的表达均显著减少，bcl-2的表达显著增加(均P<0.01)。结论: MI大鼠心肌组织中Rho激酶的表达升高，心肌细胞凋亡增加。法舒地尔能够减少Rho激酶的表达，减少心肌细胞凋亡，发挥对心肌的保护作用。
Abstract:
AIM: To analyze the changes of Rho-kinase expression in rats with acute myocardial infarction (AMI) and to study the relationship between cardiac myocyte apoptosis and Rho/Rock signaling pathway and the effect of fasudil, a Rho kinase selective inhibitor, on cardiac protection after AMI. METHODS: Male Wistar rats were subjected to left anterior descending coronary artery (LAD) ligation for 24 h and the surviving rats were randomly divided into two groups: treatment group (n=12) and AMI group (n=12). Another ten rats were randomly selected as the sham-operated group (n=10), with no ligation of LAD. Fasudil (5 mg/kg) was given to rats of the treatment group twice a day by IP injection. Rats of the AMI group and sham-operated group during the same period were given an equivalent normal of saline. Rats were sacrificed 4 weeks after and the infarct size and ischemia size were determined by Evans-blue and NBT double staining. The Rho kinase mRNA expression in the ischemia region was measured by RT-PCR and the apoptotic cardiocytes in the ischemia region were determined by DNA ladder analysis. Bcl-2 and Bax protein expressions were measured by immunohistochemical staining. RESULTS: Infarct size was obviously reduced in treatment group compared with AMI group (P<0.05) and no significant difference was observed in the ischemic area. The expression of Rho kinase increased significantly in AMI group compared with sham group. Expression of apoptosis-related protein and bax increased whereas bcl-2 decreased (P<0.01). Compared with those in AMI group, the expression of Rho kinase significantly attenuated, bax decreased and bcl-2 increased in the treatment group (P<0.01). DNA agarose gel electrophoresis of both AMI group and treatment group formed ladders, but no ladders were observed in sham group. CONCLUSION: In the myocardium of rats with AMI, the expression of Rho kinase and the apoptosis of myocardial cells are increased. Fasudil, a Rho kinase inhibitor, attenuates the expression of Rho kinase and apoptosis of myocardial cells and decreases infarct size, therefore playing an important role in cardiac protection after AMI.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2009-10-26.通讯作者：谭丽娟，副主任医师，主要从事冠心病及心力衰竭研究 Email：qdtanlijuan@126.com 作者简介：潘娜娜，硕士生Email：sarapan2007@126.com
更新日期/Last Update: 2010-10-27