培马贝特治疗对自发性糖尿病鸟脂鼠糖尿病视网膜病变的保护作用

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY Biological & pharmaceutical bulletin Pub Date : 2024-03-27 Epub Date: 2024-03-01 DOI:10.1248/bpb.b23-00872
Yoshiaki Tanaka, Rina Takagi, Shingen Mitou, Machiko Shimmura, Tetsuya Hasegawa, Jota Amarume, Masami Shinohara, Yasushi Kageyama, Tomohiko Sasase, Takeshi Ohta, Shin-Ichi Muramatsu, Akihiro Kakehashi, Toshikatsu Kaburaki
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引用次数: 0

摘要

糖尿病视网膜病变(DR)可导致视力损伤和失明,而全球糖尿病患病率的不断上升凸显了预防和治疗 DR 的有效疗法的必要性。因此,本研究旨在利用自发性糖尿病托氏(SDT)肥胖 2 型糖尿病大鼠模型,评估培马贝特治疗对 DR 的保护作用。从 SDT 脂肪大鼠 8 周大开始,连续 16 周喂食添加培马贝特(0.3 毫克/千克/天)的食物(Pf SDT 脂肪大鼠:研究组),或喂食普通饲料(SDT 脂肪大鼠:对照组)。为 Sprague-Dawley (SD) 大鼠提供正常饲料(SD:正常对照组)。分别在大鼠8周龄和24周龄时进行视网膜电图(ERG)检查,以评估视网膜神经功能。大鼠牺牲后,对视网膜厚度、视网膜皱褶数量和脉络膜厚度进行评估,并对水孔蛋白-4(AQP4)进行免疫染色。服用培马贝特后,食量、体重和血糖水平均无明显差异。甘油三酯水平降低,高密度脂蛋白胆固醇水平升高。Pf SDT脂肪组的ERG上振荡电位(OP)1和OP3波的延伸受到抑制。Pf SDT 脂肪肝组距视盘 1,500 微米处的视网膜厚度有所改善。脉络膜厚度和视网膜皱褶数量没有明显改善。定量分析显示,Pf SDT 脂肪肝组视网膜中的 AQP4 阳性区域明显大于 SDT 脂肪肝组。研究结果表明,培马贝特治疗可对DR产生保护作用。
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Protective Effect of Pemafibrate Treatment against Diabetic Retinopathy in Spontaneously Diabetic Torii Fatty Rats.

Diabetic retinopathy (DR) can cause visual impairment and blindness, and the increasing global prevalence of diabetes underscores the need for effective therapies to prevent and treat DR. Therefore, this study aimed to evaluate the protective effect of pemafibrate treatment against DR, using a Spontaneously Diabetic Torii (SDT) fatty rat model of obese type 2 diabetes. SDT fatty rats were fed either a diet supplemented with pemafibrate (0.3 mg/kg/d) for 16 weeks, starting at 8 weeks of age (Pf SDT fatty: study group), or normal chow (SDT fatty: controls). Normal chow was provided to Sprague-Dawley (SD) rats (SD: normal controls). Electroretinography (ERG) was performed at 8 and 24 weeks of age to evaluate the retinal neural function. After sacrifice, retinal thickness, number of retinal folds, and choroidal thickness were evaluated, and immunostaining was performed for aquaporin-4 (AQP4). No significant differences were noted in food consumption, body weight, or blood glucose level after pemafibrate administration. Triglyceride levels were reduced, and high-density lipoprotein cholesterol levels were increased. Extension of oscillatory potential (OP)1 and OP3 waves on ERG was suppressed in the Pf SDT fatty group. Retinal thickness at 1500 microns from the optic disc improved in the Pf SDT fatty group. No significant improvements were noted in choroidal thickness or number of retinal folds. Quantitative analyses showed that AQP4-positive regions in the retinas were significantly larger in the Pf SDT fatty group than in the SDT fatty group. The findings suggest that pemafibrate treatment can exert protective effects against DR.

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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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