Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats.
Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats.
复制标题
DOI：
10.3390/ijms24010240
复制
发表时间：
2022-12-23
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
氧化应激、神经退行性变、神经炎症和血管渗漏被认为在糖尿病视网膜病变（ESDR）的早期阶段起关键作用。本研究的目的是研究大麻素受体1（CB 1 R）的阻断和大麻素受体2（CB 2 R）的激活作为治疗DR早期毒性事件的假定疗法。（20 μL，10 mg/mL），每日一次，持续14天（早期DR模型），与SR 141716（CB 1 R拮抗剂）、AM 1710（CB 2 R激动剂）和双重治疗SR 141716/AM 1710联合给药。进行免疫组织化学-组织学、ELISA和Evans-Blue分析以评估药物治疗对糖尿病诱导的视网膜毒性的神经保护和血管保护特性。激活CB 2 R或阻断CB 1 R，以及双重治疗，减轻糖尿病引起的硝化应激。两种单一治疗都保护了神经元件（例如，RGC轴突）和减少血管渗漏。AM 1710单独逆转所有毒性损伤。这些发现提供了关于大麻素在局部给药时在治疗ESDR中的不同功效的新知识。大麻素对ESDR中糖尿病视网膜的神经保护作用可能被证明在延迟疾病晚期发展方面具有治疗作用。
Oxidative stress, neurodegeneration, neuroinflammation, and vascular leakage are believed to play a key role in the early stage of diabetic retinopathy (ESDR). The aim of this study was to investigate the blockade of cannabinoid receptor 1 (CB1R) and activation of cannabinoid receptor 2 (CB2R) as putative therapeutics for the treatment of the early toxic events in DR. Diabetic rats [streptozotocin (STZ)-induced] were treated topically (20 μL, 10 mg/mL), once daily for fourteen days (early stage DR model), with SR141716 (CB1R antagonist), AM1710 (CB2R agonist), and the dual treatment SR141716/AM1710. Immunohistochemical-histological, ELISA, and Evans-Blue analyses were performed to assess the neuroprotective and vasculoprotective properties of the pharmacological treatments on diabetes-induced retinal toxicity. Activation of CB2R or blockade of CB1R, as well as the dual treatment, attenuated the nitrative stress induced by diabetes. Both single treatments protected neural elements (e.g., RGC axons) and reduced vascular leakage. AM1710 alone reversed all toxic insults. These findings provide new knowledge regarding the differential efficacies of the cannabinoids, when administered topically, in the treatment of ESDR. Cannabinoid neuroprotection of the diabetic retina in ESDR may prove therapeutic in delaying the development of the advanced stage of the disease.