Wang Chen, Sun Hourong, Song Yi, Ma Zengshan, Zhang Gong, Gu Xinghua, Zhao Lei
School of Clinical Medicine, Fourth Military Medical University Xi'an 710032, China.
Department of Cardiovascular Surgery, Qilu Hospital of Shandong University Jinan 250012, China.
Int J Clin Exp Med. 2015 Feb 15;8(2):1737-46. eCollection 2015.
The aim of the present study was to investigate whether pterostilbene could modulate the TLR4/NF-κB signaling, reduce neutrophil accumulation and TNF-α induction in an ischemia/reperfusion injured rat heart model.
Rats were randomly exposed to sham operation, myocardial ischemia and reperfusion (MI/R), MI/R + pterostilbene, MI/R + pterostilbene + L-NAME. And myocardial infarct size, apoptosis, TLR4 expression, NF-κB expression, MPO level and TNF-α level were detected.
The results demonstrated that after MI/R, the expressions of myocardial TLR4, NF-κB and caspase-3 increased significantly in ischemia area. Compared with MI/R, pterostilbene significantly attenuated the expressions of TLR4, NF-κB and caspase-3. In addition, it also reduced myeloperoxidase (MPO) levels, both serum and myocardial TNF-α production, myocardial infarct sizes (INF/AAR%) and myocardial apoptosis induced by MI/R. All the effects of pterostilbene were abolished by L-NAME, a nitric oxide synthase inhibitor.
These data provide evidence that pterostilbene inhibits TLR4/NF-κB signaling and apoptosis in the rat heart subjected to MI/R, which is associated with NO production.
本研究旨在探讨紫檀芪是否能够调节Toll样受体4/核因子κB(TLR4/NF-κB)信号通路,减少缺血/再灌注损伤大鼠心脏模型中的中性粒细胞聚集和肿瘤坏死因子-α(TNF-α)的诱导。
将大鼠随机分为假手术组、心肌缺血再灌注组(MI/R)、MI/R + 紫檀芪组、MI/R + 紫檀芪 + N-硝基-L-精氨酸甲酯(L-NAME)组。检测心肌梗死面积、细胞凋亡、TLR4表达、NF-κB表达、髓过氧化物酶(MPO)水平和TNF-α水平。
结果表明,MI/R后,缺血区域心肌TLR4、NF-κB和半胱天冬酶-3(caspase-3)的表达显著增加。与MI/R组相比,紫檀芪显著减弱了TLR4、NF-κB和caspase-3的表达。此外,它还降低了髓过氧化物酶(MPO)水平、血清和心肌TNF-α的产生、心肌梗死面积(INF/AAR%)以及MI/R诱导的心肌细胞凋亡。紫檀芪的所有作用均被一氧化氮合酶抑制剂L-NAME消除。
这些数据表明,紫檀芪抑制MI/R大鼠心脏中的TLR4/NF-κB信号通路和细胞凋亡,这与一氧化氮的产生有关。