Anthocyanin Protects Cardiac Function and Cardiac Fibroblasts From High-Glucose Induced Inflammation and Myocardial Fibrosis by Inhibiting IL-17.

Anthocyanin Protects Cardiac Function and Cardiac Fibroblasts From High-Glucose Induced Inflammation and Myocardial Fibrosis by Inhibiting IL-17.
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花青素通过抑制 IL-17 保护心脏功能和心脏成纤维细胞免受高糖诱导的炎症和心肌纤维化的影响

DOI:
10.3389/fphar.2020.593633
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发表时间:
2020
影响因子:
5.6
通讯作者:
Yang B
Yang B
中科院分区:
医学2区
文献类型:
--
作者:
Yue E;Yu Y;Wang X;Liu B;Bai Y;Yang B

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糖尿病心肌病(DCM)是糖尿病患者死亡的主要原因之一。其发病机制涉及炎症和纤维化,损害心脏组织并损害心脏功能。白细胞介素 (IL)-17 是一种促炎细胞因子,在多种慢性炎症过程中发挥重要作用,可作为有吸引力的治疗靶点。花青素是一种水溶性天然色素,具有令人印象深刻的抗炎活性。然而,其在 DCM 中的作用尚不清楚。因此,我们利用链脲佐菌素诱导的小鼠 1 型糖尿病模型研究了花青素对糖尿病心血管并发症的保护作用。通过超声心动图、苏木精和伊红染色以及马森三色染色来测试糖尿病小鼠的心脏功能和结构改变。采用免疫组织化学方法评估糖尿病小鼠左心室组织中 IL-17 以及胶原蛋白 I 和 III 的分布和沉积。使用甲基噻唑基四唑测定法测量细胞活力。使用酶联免疫吸附测定法测定 IL-17、肿瘤坏死因子 α、IL-1β 和 IL-6 的蛋白水平。通过蛋白质印迹和免疫荧光检测IL-17以及胶原蛋白I和III,并使用定量逆转录PCR定量它们的mRNA水平。我们观察到花青素可以降低糖尿病小鼠的血糖,改善心脏功能,减轻心脏组织的炎症和纤维化。同时,花青素降低高糖处理的心脏成纤维细胞中IL-17的表达,并表现出抗炎作用。花青素还可以减少 I 型和 III 型胶原蛋白的沉积,表明花青素有助于减轻心肌纤维化。综上所述,花青素可以保护心脏功能并抑制IL-17相关的炎症和纤维化,这表明其在治疗糖尿病相关并发症方面具有治疗潜力。
Diabetic cardiomyopathy (DCM) is one of the major causes of death in diabetic patients. Its pathogenesis involves inflammation and fibrosis that damages the heart tissue and impairs cardiac function. Interleukin (IL)-17, a pro-inflammatory cytokine that plays an important role in a variety of chronic inflammatory processes can serve as an attractive therapeutic target. Anthocyanin, a water-soluble natural pigment, possesses impressive anti-inflammatory activity. However, its role in DCM is unclear. Hence, we investigated the protective effect of anthocyanin on the cardiovascular complications of diabetes using a mouse type 1 diabetes mellitus model induced by streptozotocin. Cardiac function and structural alterations in diabetic mice were tested by echocardiography, hematoxylin and eosin staining, and Masson trichrome staining. Immunohistochemistry was performed to evaluate the distribution and deposition of IL-17 and collagen I and III from the left ventricular tissues of diabetic mice. Cell viability was measured using the methyl thiazolyl tetrazolium assay. Protein levels of IL-17, tumor necrosis factor α, IL-1β, and IL-6 were determined using enzyme-linked immunosorbent assay. IL-17 and collagen I and III were detected by western blotting and immunofluorescence, and their mRNA levels were quantified using quantitative reverse transcription PCR. We observed that anthocyanin lowered blood glucose, improved cardiac function, and alleviated inflammation and fibrosis in the heart tissue of diabetic mice. Meanwhile, anthocyanin reduced the expression of IL-17 in high-glucose-treated cardiac fibroblasts and exhibited an anti-inflammatory effect. Deposition of collagen I and III was also decreased by anthocyanin, suggesting that anthocyanin contributes to alleviating myocardial fibrosis. In summary, anthocyanin could protect cardiac function and inhibit IL-17-related inflammation and fibrosis, which indicates its therapeutic potential in the treatment of diabetes mellitus-related complications.
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