Department of Pharmacology, School of Pharmacy, Second Military Medical University, Shanghai, China.
CNS Neurosci Ther. 2012 Oct;18(10):834-40. doi: 10.1111/j.1755-5949.2012.00379.x. Epub 2012 Aug 25.
To explore risk factors for stroke independent of hypertension and the relationship between riboflavin kinase (RFK) and stroke.
Gene expression profiling in the brains of spontaneously hypertensive rats (SHR) and stroke-prone spontaneously hypertensive rats (SHRSP) was comparatively analyzed by gene chips. The differentially expressed gene RFK was further verified by q-PCR and Western blot. The protective role of RFK-regulated flavins (including riboflavin, flavin mononucleotide, and flavin adenine dinucleotide) in stroke was observed in middle cerebral artery occlusion (MCAO) mice. Influence of flavins on apoptosis and death in oxygen and glucose deprivation (OGD)-treated neurons was examined by flow cytometry. Bax and Bcl-2 proteins were detected by Western blot.
Of the 76 differentially expressed genes, 41 genes were upregulated, and 35 genes were downregulated in SHRSP as compared with SHR. RFK was significantly downregulated in SHRSP. Flavins markedly decreased infarct area in MCAO mice, inhibited apoptosis and death in OGD-treated neurons, and decreased Bax protein expression.
Physiological downregulation of RFK may be a new potential risk factor for stroke, which probably affects the absorbance and utility of riboflavin and further destroys the protective effect of flavins on stroke. RFK might act as a therapeutic target for stroke.
探讨独立于高血压的中风风险因素以及核黄素激酶 (RFK) 与中风的关系。
通过基因芯片比较分析自发性高血压大鼠 (SHR) 和易发生中风的自发性高血压大鼠 (SHRSP) 大脑中的基因表达谱。进一步通过 q-PCR 和 Western blot 验证差异表达基因 RFK。在大脑中动脉闭塞 (MCAO) 小鼠中观察 RFK 调节的黄素（包括核黄素、黄素单核苷酸和黄素腺嘌呤二核苷酸）对中风的保护作用。通过流式细胞术检测黄素对氧葡萄糖剥夺 (OGD) 处理神经元中凋亡和死亡的影响。通过 Western blot 检测 Bax 和 Bcl-2 蛋白。
在 76 个差异表达基因中，与 SHR 相比，SHRSP 中有 41 个基因上调，35 个基因下调。RFK 在 SHRSP 中显著下调。黄素明显减少 MCAO 小鼠的梗死面积，抑制 OGD 处理神经元中的凋亡和死亡，并降低 Bax 蛋白表达。
RFK 的生理下调可能是中风的一个新的潜在风险因素，它可能影响核黄素的吸收和利用，并进一步破坏黄素对中风的保护作用。RFK 可能成为中风的治疗靶点。
