摘要
目的比较胰岛素样生长因子-1后处理(IGF-1-POST)与缺血后处理(I-POST)对缺血再灌注心肌的保护作用,探讨两者抑制缺血再灌注心肌凋亡的可能机制。方法采用垫扎球囊法建立模型,将48只SD大鼠随机均分成4组(n=12):假手术组、I/R组I、-POST组I、GF-1-POST组。除假手术组外其余各组均缺血45min再灌注120min。记录再灌注30min期间心脏电活动情况和再灌注120min时的血流动力学指标;用ELISA法检测血清TNF-αI、L-6和IL-10含量,HE染色观察心肌病理损伤情况,TUNEL法检测心肌凋亡情况,免疫组化及Western blotting检测Pser-133-CREB和Bcl-2蛋白表达。结果与I/R组比较,I-POST组及IGF-1-POST组心功能改善;血清TNF-α,IL-6含量下降,IL-10含量升高;ST段抬高程度、室性早搏次数、室性心律失常持续时间均减少;心肌病理损伤减轻,凋亡数量下降;Pser-133-CREB和Bcl-2蛋白表达升高,差异均有统计学意义(P<0.05)。与I-POST组比较,IGF-1-POST组TNF-α减少,IL-10增加,差异有统计学意义(P<0.05);ST段抬高程度、室性早搏次数、室性心律失常持续时间均增加,差异有统计学意义(P<0.05);两组的其他各项指标无统计学差异(P>0.05)。结论 IGF-1对缺血再灌注心肌具有后处理保护作用,其保护作用和保护程度可能与缺血后处理相似。IGF-1后处理和缺血后处理抗心肌凋亡作用可能均与Pser-133-CREB和Bcl-2蛋白高表达有关。
Objective To compare the protective effect of insulin-like growth factor-1（IGF-1） and ischemic postconditioning on ischemia-reperfusion myocardium apoptosis,and explore the possible mechanisms of inhibition of apoptosis of myocardial cells.Methods Forty eight SD rats were randomly divided into 4 groups（12 each）： sham-operation group（sham）,ischemic/reperfusion group（I/R）,ischemic postconditioning group（I-POST） and IGF-1 postconditioning group（IGF-1-POST）.The rat model was established by repeated ligation.Except the sham group,rats in the other three groups subjected to 45min of ischemia followed by 120min of reperfusion.During the first 30min of the reperfusion period,the cardiac electrical activity was recorded.In the 120th minute of the reperfusion,the hemodynamic parameters were monitored.The serous TNF-α,IL-6 and IL-10 levels were detected by ELISA.The degree of myocardial damage was observed by HE staining.Apoptosis was detected by TUNEL,and the expressions of Pser-133-CREB and Bcl-2 protein were monitored by Western blotting and immunohistochemical methods.Results Compared with that in I/R group,the cardiac function of rats in I-POST group and IGF-1-POST group was improved;the serous TNF-α and IL-6 levels were lower while IL-10 level was higher;the elevation degree of ST segment,the ventricular premature beats and the duration of ventricular arrhythmia decreased at the same time;the degree of myocardial damage lessened and the number of apoptosis cells increased;the expressions of Pser-133-CREB and Bcl-2 protein increased significantly（P0.05）.In comparison with the I-POST group,TNF-α decreased but IL-10 increased significantly in IGF-1-POST group（P0.05）;the elevation degree of ST segment,the ventricular premature beats and the duration of ventricular arrhythmia increased significantly（P0.05）.As the other aspects mentioned above,no statistical difference was found between the two groups（P0.05）.Conclusions IGF-1 may play a protective effect on ischemia-reperfusion myocardium in a similar extent to that of ischemic postconditioning.The anti-apoptosis effect of IGF-1 and ischemic postconditioning may be related with the high expressions of Pser-133-CREB and t Bcl-2 protein.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2011年第8期808-812,共5页
Medical Journal of Chinese People's Liberation Army
关键词
药物后处理
缺血后处理
缺血再灌注
凋亡
pharmacological postconditioning
ischemic postconditioning
ischemia-reperfusion
apoptosis
