摘要
目的:研究JAK2/STAT3信号通路在河豚毒素(Tetrodotoxin,TTX)心脏停搏液心肌保护中的作用。方法:24只Wistar大鼠随机分为对照组、TTX组和TTX+AG490组,每组8只。对照组:开胸取左心室肌作为缺血前对照。TTX组:建立离体心脏Langendorff-Neely灌注模型,预灌注K-H缓冲液30min后,灌注4℃TTX心脏停搏液,停搏心脏并低温维持60min,复灌K-H缓冲液60min后,取左心室肌备用。TTX+AG490组:操作同TTX组,但预灌和复灌时均在K-H缓冲液中加入JAK2抑制剂AG490(5μmol/L)。采用免疫组化法测定心肌组织中p-STAT3(磷酸化STAT3)和Bcl-2表达量(Protein expression index,PEI),TUNEL检测心肌细胞凋亡指数(Apoptosis index,AI),比较2组间的变化。结果:与对照组相比,TTX组和TTX+AG490组心肌组织中p-STAT3和Bcl-2的表达量均明显增加(P<0.05);予以AG490处理后,p-STAT3和Bcl-2的表达量较TTX组明显下降(P<0.05)。Bcl-2蛋白表达与p-STAT3蛋白表达呈正相关(r=0.743,P<0.05)。经历缺血再灌注后,TTX组和TTX+AG490组心肌细胞AI明显高于对照组(P<0.05);与TTX组相比,TTX+AG490组AI显著增加(P<0.05)。结论:JAK2/STAT3信号通路通过上调Bcl-2的表达,抑制心肌细胞凋亡,介导TTX心脏停搏液对缺血心肌的保护作用。
Objective:To investigate the effect of JAK2/STAT3 pathway on myocardial protection of tetrodotoxin (TTX) cardioplegia in rat hearts. Methods:A total of 24 Wistar rats were randomly divided into Group Control,Group TTX and Group TTX+AG490(n=8). The left ventricular samples in Group Control were collected as pre-ischemia control through thoracotomy. After isolated heart Langendorff and Neely models were established, the rat hearts in Group TTX were continuously perfused with Krebs-Henseleit(K-H) buffer solution for 30 minutes, arrested by TTX cardioplegia(4℃) for 60 minutes,and underwent reperfusion with K-H buffer solution for 60 minutes,then the left ventricular samples were collected for detections. The rat hearts in Group TTX+AG490 were perfused and reperfused with JAK2 inhibitor AG490(5μmol/L) and K-H buffer solution under the same procedure as Group TTX. The protein expression indexes(PEI) of phosphorylated-STAT3(p-STAT3) and B-cell lymphoma-2( Bcl-2 ) in myocardium were detected by immunohistochemical assay(IHC ). The apoptosis index(AI ) of cardiomyocyte was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL). The changes of these indexes in three groups were used for comparison. Results:Compared with Group Control,the PEI of p-STAT3 and Bcl-2 in Group TTX and Group TTX+AG490 increased significantly(P〈0.05);Treated with AG490,the PEI of p-STAT3 and Bcl-2 in Group TTX+AG490 was lower than that in Group TTX(P〈0.05). The PEI of Bcl-2 had a positive correlation with the PEI of p-STAT3 (r=0.743,P〈0.05). After ischemia/reperfusion,AI in Group Trx and Group TTX+AG490 were significantly higher than that in Group Control(P〈0.05);compared with Group TTX,AI in Group TTX+AG490 increased significantly(P〈0.05). Conclutions:JAK2/STAT3 pathway could mediate myocardial protection of TTX cardioplegia in rat hearts via upregulating the protein expression of Bcl-2 and suppressing cardiomyocytes apoptosis.
出处
《重庆医科大学学报》
CAS
CSCD
2008年第2期169-172,共4页
Journal of Chongqing Medical University
关键词
信号转导及转录激活因子3
Bcl-2
凋亡
河豚毒素
心肌保护
Signal transducer and activator of transcription 3
Bcl-2
Apoptosis
Tetrodotoxin
Myocardial protection