Centre for Research and Biological Evaluations (CEIEB), Institute of Pharmacy and Food, University of Havana, Ave. 23 e/ 214 y 222, La Lisa, PO Box: 430, Havana, Cuba.
Toxicol Appl Pharmacol. 2013 Oct 1;272(1):49-60. doi: 10.1016/j.taap.2013.05.021. Epub 2013 Jun 2.
Since the inflammatory response and oxidative stress are involved in the stroke cascade, we evaluated here the effects of Phycocyanobilin (PCB, the C-Phycocyanin linked tetrapyrrole) on PC12 cell survival, the gene expression and the oxidative status of hypoperfused rat brain. After the permanent bilateral common carotid arteries occlusion (BCCAo), the animals were treated with saline or PCB, taking samples 24h post-surgery. Global gene expression was analyzed with GeneChip Rat Gene ST 1.1 from Affymetrix; the expression of particular genes was assessed by the Fast SYBR Green RT-PCR Master Mix and Bioplex methods; and redox markers (MDA, PP, CAT, SOD) were evaluated spectrophotometrically. The PCB treatment prevented the H2O2 and glutamate induced PC12 cell injury assessed by the MTT assay, and modulated 190 genes (93 up- and 97 down-regulated) associated to several immunological and inflammatory processes in BCCAo rats. Furthermore, PCB positively modulated 19 genes mostly related to a detrimental pro-inflammatory environment and counteracted the oxidative imbalance in the treated BCCAo animals. Our results support the view of an effective influence of PCB on major inflammatory mediators in acute cerebral hypoperfusion. These results suggest that PCB has a potential to be a treatment for ischemic stroke for which further studies are needed.
由于炎症反应和氧化应激参与了中风级联反应,我们在此评估藻蓝蛋白(PCB,与 C-藻蓝蛋白相连的四吡咯)对 PC12 细胞存活、基因表达和低灌注大鼠大脑氧化状态的影响。在永久性双侧颈总动脉闭塞(BCCAo)后,动物用生理盐水或 PCB 处理,在手术后 24 小时取样。Affymetrix 的 GeneChip Rat Gene ST 1.1 分析了全局基因表达;通过 Fast SYBR Green RT-PCR Master Mix 和 Bioplex 方法评估了特定基因的表达;并通过分光光度法评估了氧化还原标志物(MDA、PP、CAT、SOD)。PCB 处理可预防 H2O2 和谷氨酸诱导的 PC12 细胞损伤,通过 MTT 测定评估,并调节了 190 个基因(93 个上调和 97 个下调),这些基因与 BCCAo 大鼠的几种免疫和炎症过程有关。此外,PCB 还积极调节了 19 个主要与有害促炎环境相关的基因,并纠正了治疗 BCCAo 动物的氧化失衡。我们的研究结果支持 PCB 对急性脑低灌注主要炎症介质的有效影响的观点。这些结果表明 PCB 具有治疗缺血性中风的潜力,需要进一步研究。