Calcium Dobesilate (CaD) Attenuates High Glucose and High Lipid-Induced Impairment of Sarcoplasmic Reticulum Calcium Handling in Cardiomyocytes.
Calcium Dobesilate (CaD) Attenuates High Glucose and High Lipid-Induced Impairment of Sarcoplasmic Reticulum Calcium Handling in Cardiomyocytes.
复制标题
羟苯磺酸钙 (CaD) 可减轻高血糖和高脂质引起的心肌细胞肌浆网钙处理损伤
DOI：
10.3389/fcvm.2021.637021
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发表时间：
2021
影响因子：
3.6
通讯作者：
Yan D
中科院分区：
文献类型：
--
作者：
Deng J;Cai X;Hao M;Liu X;Chen Z;Li H;Liu J;Liao Y;Fu H;Chen H;Qin G;Yan D
羟苯磺酸钙（CaD）可有效用于糖尿病微血管疾病、视网膜病变和肾病患者。在这里，我们试图确定它是否对糖尿病性心肌病的特征性心肌细胞钙处理不当有影响。无菌分离并培养1 - 3天新生大鼠的心肌细胞，并用溶剂（对照）、25 mM葡萄糖+300 μM棕榈酸（HG+PA）、100 μM CaD（CaD）或HG+PA+CaD处理，以通过共聚焦成像测试对钙信号传导（Ca 2+火花、瞬变和SR负荷）和活性氧（ROS）产生的影响。与对照组相比，HG+PA处理显著降低了场刺激诱导的钙瞬变幅度（2.22 ± 0.19 vs.3.56 ± 0.21，p < 0.01）和咖啡因诱导的钙瞬变水平（3.19 ± 0.14 vs. 3.72 ± 0.15，p < 0.01），然而，在单个心肌细胞中显著增加自发性Ca 2+火花放电水平（自发频率2.65 ± 0.23 vs. 1.72 ± 0.12，p < 0.01）和ROS产生（67.12 ± 4.4 vs.47.65 ± 2.12，p < 0.05），表明HG+PA处理增加自发性Ca 2+火花频率，引起心肌细胞SR内Ca ~（2+）含量的部分降低，进而减弱心肌细胞收缩期Ca ~（2+）瞬变。值得注意的是，这些钙信号传导和ROS产生的损害在很大程度上通过用CaD预处理细胞来防止。因此，CaD可能有助于对糖尿病心肌病相关心肌细胞中钙处理不当和收缩功能障碍的患者具有良好的保护作用。
Calcium dobesilate (CaD) is used effectively in patients with diabetic microvascular disorder, retinopathy, and nephropathy. Here we sought to determine whether it has an effect on cardiomyocytes calcium mishandling that is characteristic of diabetic cardiomyopathy. Cardiomyocytes were sterile isolated and cultured from 1 to 3 days neonatal rats and treated with vehicle (Control), 25 mM glucose+300 μM Palmitic acid (HG+PA), 100 μM CaD (CaD), or HG+PA+CaD to test the effects on calcium signaling (Ca2+ sparks, transients, and SR loads) and reactive oxygen species (ROS) production by confocal imaging. Compared to Control, HG+PA treatment significantly reduced field stimulation-induced calcium transient amplitudes (2.22 ± 0.19 vs. 3.56 ± 0.21, p < 0.01) and the levels of caffeine-induced calcium transients (3.19 ± 0.14 vs. 3.72 ± 0.15, p < 0.01), however significantly increased spontaneous Ca2+ sparks firing levels in single cardiomyocytes (spontaneous frequency 2.65 ± 0.23 vs. 1.72 ± 0.12, p < 0.01) and ROS production (67.12 ± 4.4 vs. 47.65 ± 2.12, p < 0.05), which suggest that HG+PA treatment increases the Spontaneity Ca2+ spark frequency, and then induced partial reduction of SR Ca2+ content and subsequently weaken systolic Ca2+ transient in cardiomyocyte. Remarkably, these impairments in calcium signaling and ROS production were largely prevented by pre-treatment of the cells with CaD. Therefore, CaD may contribute to a good protective effect on patients with calcium mishandling and contractile dysfunction in cardiomyocytes associated with diabetic cardiomyopathy.