Division of Meridian and Structural Medicine, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea.
Int J Mol Med. 2013 Dec;32(6):1303-10. doi: 10.3892/ijmm.2013.1511. Epub 2013 Sep 27.
In this study, we investigated the molecular mechanisms underlying the anti-apoptotic properties of electroacupuncture (EA) in a rat model of middle cerebral artery occlusion (MCAO). Treatment with 2 Hz EA (1 mA) resulted in a markedly reduced infarct area after stroke, particularly in the middle region of the brain. Treatment with EA resulted in a significant decrease in the number of apoptotic cells identified by Hoechst 33342 and TUNEL staining. According to the results of the analysis for proteins involved in apoptosis, treatment with EA resulted in a significantly reduced expression of death receptor (DR)5. Among the members of the Bcl‑2 family, a higher expression of anti-apoptotic Bcl‑2 and Bcl‑xL was observed in the rats treated with EA, compared with the untreated rats with MCAO. As regards the expression of the inhibitor of apoptosis protein (IAP) family, a higher expression of anti-apoptotic cIAP‑1 and ‑2 was also detected in the cortex of the EA‑treated rats. Using western blot analysis, we observed that activated caspase‑3 was only significantly arrested by EA treatment in the rats with MCAO; however, according to the results of the caspase assay, the activities of caspase‑3, ‑8 and ‑9 were markedly inhibited by EA treatment. These results suggest that treatment with EA exerts anti‑apoptotic effects in cerebral ischemia in a rat model of MCAO and that these effects are associated with the inhibition of the DR and mitochondrial apoptotic pathways.
在这项研究中,我们研究了电针(EA)在大脑中动脉闭塞(MCAO)大鼠模型中抗细胞凋亡作用的分子机制。接受 2 Hz EA(1 mA)治疗的大鼠在中风后梗死面积明显减小,尤其是大脑中部。EA 治疗可显著减少 Hoechst 33342 和 TUNEL 染色鉴定的凋亡细胞数量。根据参与凋亡的蛋白分析结果,EA 治疗可显著降低死亡受体(DR)5 的表达。在 Bcl-2 家族成员中,与未经 EA 治疗的 MCAO 大鼠相比,EA 治疗的大鼠中抗凋亡 Bcl-2 和 Bcl-xL 的表达更高。关于凋亡抑制蛋白(IAP)家族的表达,经 EA 治疗的大鼠皮质中抗凋亡 cIAP-1 和 cIAP-2 的表达也更高。通过 Western blot 分析,我们观察到激活的 caspase-3 仅在 MCAO 大鼠的 EA 治疗中被显著抑制;然而,根据 caspase 测定的结果,caspase-3、caspase-8 和 caspase-9 的活性被 EA 治疗明显抑制。这些结果表明,EA 治疗在 MCAO 大鼠模型中的脑缺血中发挥抗细胞凋亡作用,这些作用与抑制 DR 和线粒体凋亡途径有关。