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柚皮素通过 EETs-PPARs 激活对链脲佐菌素诱导的糖尿病小鼠的心脏肥大发挥保护作用。

Naringenin exhibits the protective effect on cardiac hypertrophy via EETs-PPARs activation in streptozocin-induced diabetic mice.

机构信息

Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing, 400016, China.

Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Guizhou, 563003, China.

出版信息

Biochem Biophys Res Commun. 2018 Jul 7;502(1):55-61. doi: 10.1016/j.bbrc.2018.05.119. Epub 2018 May 24.

Abstract

Cardiac hypertrophy is one of the key structural changes in diabetic cardiomyopathy. Naringenin, a dihydroflavonoid extracted from citrus plants with multiple pharmacological activities, yet the underlying effects on diabetic cardiac hypertrophy remain unclear. This study aimed to evaluate the potential effects of naringenin on cardiac hypertrophy in diabetic mice. Long-term high-fat feeding combined with streptozotocin resulted in cardiac hypertrophy after a diabetic model has been established for 4 weeks in mice, which were improved by naringenin supplementation (25 or 75 mg/kg/day, i. g.) for another 4 weeks. The protein and mRNA expressions of PPARs were down-regulated, the protein express of CYP2J3 and level of 14, 15-EET were decreased following diabetic cardiac hypertrophy. Naringenin administration up-regulated PPARs expression, elevated CYP2J3 protein and 14,15-EET content. In conclusion, naringenin can improve cardiac hypertrophy in diabetic mice, which may be related to up-regulate the expression of CYP2J3, elevate the level of EETs, and activate the expression of PPARs.

摘要

心肌肥厚是糖尿病心肌病的关键结构改变之一。柚皮素是从柑橘类植物中提取的二氢黄酮类化合物,具有多种药理活性,但对糖尿病性心肌肥厚的潜在作用尚不清楚。本研究旨在评估柚皮素对糖尿病小鼠心肌肥厚的潜在影响。长期高脂喂养联合链脲佐菌素(streptozotocin)处理 4 周后,建立了糖尿病小鼠模型,随后给予柚皮素(25 或 75mg/kg/天,灌胃)补充 4 周,改善了心肌肥厚。糖尿病性心肌肥厚时,PPARs 的蛋白和 mRNA 表达下调,CYP2J3 蛋白表达和 14、15-EET 水平降低。柚皮素给药可上调 PPARs 表达,增加 CYP2J3 蛋白和 14、15-EET 含量。总之,柚皮素可改善糖尿病小鼠的心肌肥厚,这可能与上调 CYP2J3 的表达、提高 EETs 的水平以及激活 PPARs 的表达有关。

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