We investigated whether low-dose phloretin served as daily dietary supplements could ameliorate diabetic atherosclerosis and the role of kruppel-like factor 2 (KLF2). HUVECs cultured in high glucose medium were treated with different concentrations of phloretin and KLF2 mRNA, and protein level was detected. Diabetes was induced using streptozotocin in Apoe-/- mice after which they were fed a high-cholesterol diet for 8 weeks. Diabetic mice injected with KLF2 shRNA-lentivirus or control virus were treated with 20 mg/kg phloretin. Glucose, lipid profile, aortic atheroma, and endothelial nitric oxide synthase (eNOS) expression were detected. Phloretin retained endothelial function by KLF2-eNOS activation under hyperglycemia. Low-dose phloretin helped with lipid metabolism, and blocked the acceleration of atherosclerosis in STZ-induced diabetic mice since the early stage, which was diminished by KLF2 knockdown. Low-dose phloretin exhibited athero-protective effect in diabetic Apoe-/- mice dependent on KLF2 activation. This finding makes phloretin for diabetic atherosclerosis.

中文翻译：

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低剂量的促肾上腺皮质激素通过内皮KLF2修复减轻糖尿病性动脉粥样硬化。

我们调查了低剂量的促胰泌素激素是否可以作为每日膳食补充剂来改善糖尿病性动脉粥样硬化和kruppel样因子2（KLF2）的作用。在高葡萄糖培养基中培养的HUVECs用不同浓度的促绿素和KLF2 mRNA处理，并检测蛋白质水平。在Apoe-/-小鼠中使用链脲佐菌素诱导糖尿病，然后给它们喂高胆固醇饮食8周。注射了KLF2 shRNA慢病毒或对照病毒的糖尿病小鼠用20 mg / kg促肾上腺皮质激素治疗。检测到葡萄糖，脂质分布，主动脉粥样硬化和内皮型一氧化氮合酶（eNOS）的表达。在高血糖情况下，磷脂通过KLF2-eNOS激活保留了内皮功能。低剂量的促性腺激素有助于脂质代谢，并从早期开始就阻止了STZ诱导的糖尿病小鼠动脉粥样硬化的加速，而后者被KLF2抑制作用减弱了。低剂量的促肾上腺皮质激素在依赖于KLF2激活的糖尿病Apoe-/-小鼠中表现出动脉粥样硬化保护作用。这一发现使phloretin可用于糖尿病动脉粥样硬化。