Academic Journal
R-(+)-WIN55212-2 protects pericytes from ischemic damage and restores retinal microcirculatory patency after ischemia/reperfusion injury
العنوان: | R-(+)-WIN55212-2 protects pericytes from ischemic damage and restores retinal microcirculatory patency after ischemia/reperfusion injury |
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المؤلفون: | Jiaojiao Wei, Lili Zhang, Kaicheng Wu, Jian Yu, Fengjuan Gao, Jingyi Cheng, Ting Zhang, Xujiao Zhou, Yuan Zong, Xiaojing Huang, Chunhui Jiang |
المصدر: | Biomedicine & Pharmacotherapy, Vol 166, Iss , Pp 115197- (2023) |
بيانات النشر: | Elsevier |
سنة النشر: | 2023 |
المجموعة: | Directory of Open Access Journals: DOAJ Articles |
مصطلحات موضوعية: | Cannabinoid, Ischemia/reperfusion injury, Retinal microcirculatory, Pericytes, Therapeutics. Pharmacology, RM1-950 |
الوصف: | Background and purpose: Cannabinoids are vasoactive substances that act as key regulators of arterial tone in the blood vessels supplying peripheral tissues and the central nervous system. This study aimed to investigate the potential of R-(+)-WIN55212-2 (WIN), a cannabinoid receptor 1 agonist (CB1), as a treatment for retinal ischemia/reperfusion (I/R) injury. Experimental approach: Male Wistar rats were subjected to retinal I/R injury by increasing intraocular pressure in the anterior chamber. The rats were randomly divided into four groups: normal control, I/R, vehicle (pre-treated with dimethyl sulfoxide [DMSO] via intraperitoneal injection), and experimental (pre-treated with WIN at a dose of 1 ml/kg via intraperitoneal injection). The rats were sacrificed at different time points of reperfusion (1 hour, 3 hours, 6 hours, and 1 day) after inducing retinal I/R injury, and their retinas were collected for analysis. Oxygen-glucose deprived/reperfusion (OGD/R) was performed by initially perfusing the retinas with oxygenated artificial cerebrospinal fluid (ACSF), then switching to an OGD solution to simulate ischemia, followed by another perfusion with ACSF. Pericyte contraction and the ''no-reflow'' phenomenon were observed using infrared differential interference contrast (IR-DIC) microscopy and immunohistochemistry. Western blot, enzyme-linked immunosorbent assay (ELISA), and nitric oxide (NO) detection were used to explore the potential mechanism. Key results: In both the OGD/R and I/R models, retinal pericytes exhibited persistent contraction even after reperfusion. The ability of WIN to regulate the tone of retinal pericytes and capillaries was specifically blocked by the BKCa inhibitor iberiotoxin (100 nM). WIN demonstrated a protective effect against retinal I/R injury by preserving blood flow in vessels containing pericytes. Pretreatment with WIN alleviated the persistent contraction and apoptosis of retinal pericytes in I/R-induced rats, accompanied by a reduction in intracellular calcium ion (Ca2+) ... |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 0753-3322 |
Relation: | http://www.sciencedirect.com/science/article/pii/S0753332223009885; https://doaj.org/toc/0753-3322; https://doaj.org/article/3205b9a7674c4b3b946a1ed4f2016e68 |
DOI: | 10.1016/j.biopha.2023.115197 |
الاتاحة: | https://doi.org/10.1016/j.biopha.2023.115197 https://doaj.org/article/3205b9a7674c4b3b946a1ed4f2016e68 |
رقم الانضمام: | edsbas.3C25C216 |
قاعدة البيانات: | BASE |
تدمد: | 07533322 |
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DOI: | 10.1016/j.biopha.2023.115197 |