Yu Huan, Zhou Dan, Wang Wei, Wang Qingxia, Li Min, Ma Xiaoyun
Graduate School of Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Zhoupu Hospital, Shanghai University of Medicine and Health Sciences, Shanghai, China.
Front Pharmacol. 2024 Oct 31;15:1443472. doi: 10.3389/fphar.2024.1443472. eCollection 2024.
The damage or apoptosis of retinal ganglion cells (RGCs) is one of the leading causes of various blinding eye diseases, such as glaucoma, diabetic retinopathy, optic neuritis, and ischemic optic neuropathy. Oxidative stress is involved in RGCs death. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis, has various beneficial effects, including anti-inflammatory, anti-apoptotic, and antioxidant properties. However, the effects of baicalin on RGCs and the underlying mechanisms require further investigation.
In this study, a glutamate-induced oxidative stress damage model of R28 cells and a rat retinal injury model were established to investigate the effects of baicalin on oxidative stress damage to RGCs and try to elucidate the underlying mechanism.
experiments demonstrated that the survival rate of R28 cells after glutamate treatment dropped to 33.4%, while 10 μM baicalin significantly inhibited glutamate-induced damage in RGCs ( < 0.001) and enhanced cell viability through decreasing ROS levels, increasing antioxidant enzyme activity, and suppressing the expression of inflammatory factors iNOS, TNF-α, IL-6, and IL-1β ( < 0.001). , baicalin effectively mitigated structural damage to retinal tissue and RGCs morphology induced by glutamate, increasing the thickness of the retinal ganglion cell layer, improving RGCs density, and reducing overall retinal thinning in rats ( 0.001) in a time- and dose-dependent effects. Mechanistic studies revealed that glutamate evaluated the phosphorylation levels of JAK/STAT, while baicalin effectively inhibited the activation of the JAK/STAT signaling pathway.
This study confirmed that baicalin protects against glutamate-induced oxidative stress damage in RGCs. It effectively alleviates oxidative stress and inflammatory responses, reduces cell apoptosis, and improves the pathological changes in the retina of rat models of RGCs damage, thereby decreasing RGCs death. Further exploration of its mechanism revealed that baicalin effectively inhibits the JAK/STAT signaling pathway, protecting RGCs from oxidative stress damage. This provides an experimental basis for the application of baicalin in the treatment of RGCs damage.
视网膜神经节细胞（RGCs）的损伤或凋亡是青光眼、糖尿病视网膜病变、视神经炎和缺血性视神经病变等各种致盲眼病的主要原因之一。氧化应激参与RGCs的死亡过程。黄芩苷是从黄芩中提取的一种黄酮类化合物，具有多种有益作用，包括抗炎、抗凋亡和抗氧化特性。然而，黄芩苷对RGCs的影响及其潜在机制尚需进一步研究。
本研究建立了谷氨酸诱导的R28细胞氧化应激损伤模型和大鼠视网膜损伤模型，以研究黄芩苷对RGCs氧化应激损伤的影响，并试图阐明其潜在机制。
实验表明，谷氨酸处理后R28细胞的存活率降至33.4%，而10 μM黄芩苷显著抑制谷氨酸诱导的RGCs损伤（P<0.001），并通过降低活性氧水平、增加抗氧化酶活性和抑制炎症因子iNOS、TNF-α、IL-6和IL-1β的表达来提高细胞活力（P<0.001）。此外，黄芩苷有效地减轻了谷氨酸诱导的视网膜组织结构损伤和RGCs形态改变，增加了视网膜神经节细胞层的厚度，提高了RGCs密度，并在大鼠中减少了整体视网膜变薄（P<0.001），呈现出时间和剂量依赖性效应。机制研究表明，谷氨酸评估了JAK/STAT的磷酸化水平，而黄芩苷有效地抑制了JAK/STAT信号通路的激活。
本研究证实黄芩苷可保护RGCs免受谷氨酸诱导的氧化应激损伤。它有效地减轻氧化应激和炎症反应，减少细胞凋亡，并改善RGCs损伤大鼠模型视网膜的病理变化，从而减少RGCs死亡。对其机制的进一步探索表明，黄芩苷有效地抑制JAK/STAT信号通路，保护RGCs免受氧化应激损伤。这为黄芩苷在治疗RGCs损伤中的应用提供了实验依据。
