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木犀草素通过ERK/PP1a/PLB/SERCA2a/JNK通路对缺血/再灌注心肌保护的研究

发表时间:2014-06-15  浏览量:1712  下载量:764
全部作者: 徐通达,吴鑫,李东野,朱莎莎,陈秋平
作者单位: 徐州医学院心血管病研究所
摘 要: 目的:通过建立大鼠心肌细胞缺血/再灌注(ischemia/reperfusion, I/R)模型,以单个心肌细胞的收缩功能、凋亡相关蛋白,以及ERK1/2和JNK通路上相关蛋白的表达变化为指标,验证木犀草素(luteolin, Lut)的心肌保护作用及机制。方法:应用大鼠心肌细胞,模拟I/R过程,并分为以下各组:1) DMSO组;2) I/R组;3) Lut预处理组(Lut+I/R);4) PD98059(PD,ERK1/2抑制剂)预处理组(PD+I/R);5) PD+Lut 预处理组(PD+Lut+I/R);6) SP600125(SP,JNK抑制剂)预处理组(SP+I/R)。检测单个细胞收缩幅度,Western blotting检测Bcl-2,Bax,ERK1/2,p-ERK1/2,JNK,p-JNK,PP1a,p-PP1a,PLB,p-PLB及SERCA2a蛋白表达变化。结果:Lut及SP预处理后能够不同程度地改善细胞收缩幅度,增加Bcl-2/Bax的比值。其中,Lut可影响收缩相关蛋白PP1a,PLB及SERCA2a的表达,SP预处理前后未见对上述收缩蛋白的表达有影响。而在Lut之前用PD干预后其保护作用可部分被阻断。结论:Lut通过ERK1/2通道调节凋亡蛋白Bcl-2,Bax和收缩相关蛋白p-ERK1/2,SERCA2a,p-PLB及p-PP1a的表达,进而发挥心脏保护功能。
关 键 词: 内科学;木犀草素;缺血/再灌注;心肌收缩功能;ERK1/2通路;JNK通路
Title: Protection of luteolin on rat cardiomyocytes following ischemia/reperfusion through ERK/PP1a/PLB/SERCA2a/JNK pathways
Author: XU Tongda, WU Xin, LI Dongye, ZHU Shasha, CHEN Qiuping
Organization: Research Institute of Cardiovascular Diseases, Xuzhou Medical College
Abstract: Objective: In order to analysize the possible molecular mechanisms that luteolin (Lut) improves contractile function of rat cardiomyocytes during ischemia-reperfusion (I/R) through ERK1/2 and JNK pathways by the assay of cardiomyocytes shortening amplitude and some related apoptosis proteins. Methods: The hearts of the normal rats were further isolated into single ventricular myocytes to simulate the I/R process using the following groups: 1) DMSO group; 2) I/R group; 3) Lut+I/R group; 4) PD98059 pretreatment (PD+I/R) group; 5) PD +Lut+I/R group; 6) SP600125 pretreatment (SP+I/R) group. The cells were harvested for measuring of single cardiomyocyte shortening amplitude and Western blotting assay checked the expression of Bcl-2, Bax, ERK1/2, p-ERK1/2, JNK, p-JNK, PP1a, p-PP1a, PLB, p-PLB and sarcoplasmic reticulum calcium-ATPase (SERCA2a). Results: Lut and SP pretrearment could improve the cell cardiomyocyte shortening amplitude and increase the Bcl-2/Bax ration. Lut affected the expression of the shortening relevant proteins PP1a, PLB and SERCA2a. However, SP pretreatment had no effect on contract related proteins. Administration of PD before Lut significantly reversed the protection of Lut. Conclusion: The protect effect of Lut is related to the expression of Bcl-2, Bax, p-ERK1/2, p-PP1a, SERCA2a and p-PLB, at least in part, by activation of the ERK1/2 signal pathway, and thus protects the function of the heart.
Key words: internal medicine; luteolin; ischemia/reperfusion; contraction function; ERK1/2 pathway; JNK pathway
发表期数: 2014年6月第11期
引用格式: 徐通达,吴鑫,李东野,等. 木犀草素通过ERK/PP1a/PLB/SERCA2a/JNK通路对缺血/再灌注心肌保护的研究[J]. 中国科技论文在线精品论文,2014,7(11):1023-1030.
 
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