Resveratrol attenuates retinal ganglion cell loss in a mouse model of retinal ischemia reperfusion injury via multiple pathways
Resveratrol attenuates retinal ganglion cell loss in a mouse model of retinal ischemia reperfusion injury via multiple pathways
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白藜芦醇通过多种途径减轻视网膜缺血再灌注损伤小鼠视网膜神经节细胞丢失
DOI：
10.1016/j.exer.2021.108683
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发表时间：
2021-06-30
影响因子：
3.4
通讯作者：
Xing, Yiqiao
中科院分区：
文献类型：
--
作者：
Ji, Kaibao;Li, Zongyuan;Xing, Yiqiao
背景资料：白藜芦醇（RES）是一种天然多酚，已被证明可以保护视网膜缺血再灌注（I/R）损伤后的视网膜神经节细胞（RGC）。然而，白藜芦醇功能的分子机制尚未完全阐明。因此，本研究探讨了白藜芦醇在体内的潜在机制。方法：建立成年雄性C57 BL/6 J小鼠视网膜缺血再灌注损伤模型。腹腔注射白藜芦醇连续5天。通过Brn 3a免疫荧光染色确定RGC存活。闪光视网膜电图（ERG）进行评估的视觉功能。Western blot检测HIF-1a、VEGF、p38、p53、PI 3 K、Akt、Bax、Bcl 2、Cleaved Caspase 3蛋白表达。结果：RES治疗可明显改善I/R损伤后7 d视网膜厚度损伤，增加Brn 3a染色的RGCs。我们还发现，管理RES显着抑制上调线粒体凋亡相关蛋白Bax和切割Caspase 3，以及增加Bcl 2的表达。此外，RES给药显著抑制I/R损伤诱导的HIF-1a/ VEGF和p38/p53通路的上调，同时激活I/R损伤诱导的PI 3 K/Akt通路的下调。此外，RES给药显著改善I/R损伤诱导的功能障碍后的视网膜功能。结论：我们的数据表明，白藜芦醇可以通过抑制HIF-1 α/VEGF和p38/p53通路，同时激活PI 3 K/ Akt通路来减轻视网膜缺血损伤诱导的RGC丢失和视网膜功能损害。因此，我们的研究结果进一步证实了白藜芦醇具有治疗青光眼的潜力。
Background: Resveratrol (RES) is a natural polyphenol that has been shown to protect retinal ganglion cells (RGCs) following retinal ischemia reperfusion (I/R) injury. However, the molecular mechanisms of resveratrol function are yet to be fully elucidated. Thus, this study explored the potential mechanisms of resveratrol in vivo. Methods: A retinal ischemia reperfusion injury model was established in adult male C57BL/6 J mice. Intraperitoneal injection of resveratrol was administered continuously for 5 days. RGC survival was determined by immunofluorescence staining with Brn3a. Flash electroretinography (ERG) was conducted to assess visual function. Proteins of HIF-1a, VEGF, p38, p53, PI3K, Akt, Bax, Bcl2, and Cleaved Caspase3 were detected using Western blot. Results: RES administration significantly ameliorated retinal thickness damage and increased Brn3a stained RGCs 7 days after I/R injury. We also found that administration of RES remarkably inhibited the upregulation of mitochondrial apoptosis-related protein Bax and Cleaved Caspase3, as well as increased the expression of Bcl2. Furthermore, RES administration significantly suppressed the I/R injury-induced upregulation of the HIF-1a/ VEGF and p38/p53 pathways, while activating the I/R injury-induced downregulation of the PI3K/Akt pathway. Moreover, RES administration remarkably improved retinal function after I/R injury-induced functional impairment. Conclusions: Our data demonstrated that resveratrol can mitigate retinal ischemic injury induced RGC loss and retinal function impairment by inhibiting the HIF-1a/VEGF and p38/p53 pathways while activating the PI3K/ Akt pathway. Therefore, our results further reinforce that resveratrol has potential for treating glaucoma.