Department of Cardiovascular Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032., China.
Diabetes Obes Metab. 2010 Apr;12(4):316-22. doi: 10.1111/j.1463-1326.2009.01166.x.
Diabetes Mellitus (DM) is widely acknowledged to increase the risk of cardiovascular death, which warrants the use of aggressive primary prevention strategies. The aim of the present study was to investigate the pretreatment effects of tanshinone IIA (TSN), a traditional Chinese medicine, on myocardial infarct size, apoptosis, inflammation and cardiac functional recovery in diabetic rats subjected to myocardial ischaemia/reperfusion (I/R).
Streptozocin (STZ) induced diabetic rats (n = 80) were randomized to receive TSN, TSN plus wortmannin [a phosphatidylinositol 3-kinase (PI3K) inhibitor] or saline. They were exposed to a 30-min ischaemia by ligation of the left coronary artery except for the sham group. Haemodynamics, infarct size and myocardial apoptosis were examined 3 h after reperfusion. The effects of TSN on Akt and NF-kappaB phosphorylation and the expression of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in cardiac tissues were examined.
Our results revealed that TSN administration significantly reduced myocardial infarct size (0.252 +/- 0.038 vs. 0.327 +/- 0.027, p < 0.05), improved left ventricular ejection fraction (LVEF) (0.774 +/- 0.058 vs. 0.716 +/- 0.054, p < 0.05), decreased myocardial apoptotic death (0.114 +/- 0.026 vs. 0.191 +/- 0.023, p < 0.05) compared with I/R group. Western blot analysis showed that TSN treatment enhanced Akt phosphorylation and inhibited NF-kappaB phosphorylation in cardiac tissues. Moreover, pretreatment with wortmannin abolished the beneficial effects of TSN: a reduction of infarct size, a decrease in LVEF, inhibition of myocardial apoptosis and Akt phosphorylation, enhancement of NF-kappaB phosphorylation and an increase of cytokine production including TNF-alpha and IL-6 after I/R injury in diabetic rats.
This study indicates that TSN pretreatment reduces infarct size and improves cardiac dysfunction after I/R injury in diabetic rats. This was accompanied with decreased cardiac apoptosis and inflammation. The possible mechanism responsible for the effects of TSN is associated with the PI3K/Akt-dependent pathway.
糖尿病（DM）被广泛认为会增加心血管死亡的风险，因此需要采用积极的一级预防策略。本研究的目的是探讨丹参酮 IIA（TSN）预处理对糖尿病大鼠心肌缺血/再灌注（I/R）后心肌梗死面积、细胞凋亡、炎症和心功能恢复的影响。
链脲佐菌素（STZ）诱导的糖尿病大鼠（n=80）随机分为 TSN 组、TSN+wortmannin 组（PI3K 抑制剂）和生理盐水组。除假手术组外，结扎左冠状动脉 30 分钟造成缺血。再灌注 3 小时后检测血流动力学、梗死面积和心肌细胞凋亡。检测 TSN 对心肌组织中 Akt 和 NF-κB 磷酸化以及肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）表达的影响。
TSN 给药显著减少心肌梗死面积（0.252±0.038 比 0.327±0.027，p<0.05），改善左心室射血分数（LVEF）（0.774±0.058 比 0.716±0.054，p<0.05），减少心肌细胞凋亡（0.114±0.026 比 0.191±0.023，p<0.05），与 I/R 组相比。Western blot 分析显示，TSN 处理增强了心肌组织中 Akt 的磷酸化，抑制了 NF-κB 的磷酸化。此外，wortmannin 预处理消除了 TSN 的有益作用：减少梗死面积、降低 LVEF、抑制心肌细胞凋亡和 Akt 磷酸化、增强 NF-κB 磷酸化以及增加糖尿病大鼠 I/R 损伤后细胞因子（TNF-α和 IL-6）的产生。
本研究表明，TSN 预处理可减少糖尿病大鼠 I/R 损伤后的梗死面积和改善心功能。这伴随着心脏凋亡和炎症的减少。TSN 作用的可能机制与 PI3K/Akt 依赖性途径有关。
