The present investigation evaluated the effect of inhibiting the P2Y12 gene on anaesthetic-induced neuronal injury in a rat model. Neuronal injury was induced by exposing the animals for 6 h to 30% oxygen containing 0.75% isoflurane and 1.2 mg/kg prasugrel (a P2Y12 inhibitor) p.o. for 14 days. Cognitive function was determined by the Morris water maze, and the neurological severity score was determined. Enzyme-linked immunosorbent assay was used to estimate the level of oxidative stress and mediators of inflammation in brain tissues of isoflurane-induced neuronal injury rats. Apoptosis of neuronal cells was estimated by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and western blot assays. Real time-polymerase chain reaction was performed to estimate the expression levels of several proteins. The data revealed that inhibiting the P2Y12 gene ameliorated changes in the modified neurological severity score and cognitive function in neuronal injury rats. Moreover the levels of proinflammatory mediators, oxidative stress, and cyclic AMP, and the number of TUNEL-positive cells, decreased significantly (p < 0.01) in the prasugrel-treated group compared to the negative control group. In addition, apoptosis of neuronal cells decreased in the prasugrel-treated group, as it ameliorated expression of the PI3K, Bcl-2, Bad, and Akt proteins in the isoflurane-induced neuronal injury rats. Expression of brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) proteins was enhanced, whereas the Toll-like receptor-4 (TLR-4) and nuclear factor κB (NF-κB) proteins decreased in the brain tissues of the prasugrel-treated group compared to the negative control group of rats. These results suggest that inhibiting the P2YR12 gene protects against neuronal injury in isoflurane-induced neuronal injury rats. Inhibiting the P2YR12 gene ameliorated neuronal apoptosis by regulating the BDNF/TLR-4/TNF-α pathway.

中文翻译：

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P2YR12的失活通过改变TLR-4 / BDNF /TNF-α促进异氟烷诱导的神经元损伤。

本研究评估了在大鼠模型中抑制P2Y12基因对麻醉药诱导的神经元损伤的作用。将动物暴露于含0.75％异氟烷和1.2 mg / kg普拉格雷（一种P2Y12抑制剂）的30％氧气中6小时，可引起神经元损伤，持续14天。莫里斯水迷宫确定认知功能，并确定神经系统严重程度评分。酶联免疫吸附法用于评估异氟烷诱导的神经元损伤大鼠脑组织中的氧化应激水平和炎症介质。神经元细胞的凋亡通过末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）和Western blot分析进行评估。进行实时聚合酶链反应以估计几种蛋白质的表达水平。数据显示，抑制P2Y12基因可改善神经元损伤大鼠神经功能严重程度评分和认知功能的改变。此外，普拉格雷治疗组与阴性对照组相比，促炎介质，氧化应激和环状AMP的水平以及TUNEL阳性细胞的数量显着降低（p <0.01）。另外，普拉格雷治疗组神经元细胞凋亡减少，因为它改善了异氟烷诱导的神经元损伤大鼠中PI3K，Bcl-2，Bad和Akt蛋白的表达。脑源性神经营养因子（BDNF）和原肌球蛋白受体激酶B（TrkB）蛋白的表达增强，与普拉提格雷治疗组相比，普拉格雷治疗组的脑组织中Toll样受体4（TLR-4）和核因子κB（NF-κB）蛋白降低。这些结果表明，抑制P2YR12基因可防止异氟烷诱导的神经元损伤大鼠的神经元损伤。抑制P2YR12基因可通过调节BDNF / TLR-4 /TNF-α途径改善神经元凋亡。