Calcium Dobesilate (CaD) Attenuates High Glucose and High Lipid-Induced Impairment of Sarcoplasmic Reticulum Calcium Handling in Cardiomyocytes

摘要

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 (Ca 2+ 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 Ca 2+ 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 Ca 2+ spark frequency, and then induced partial reduction of SR Ca 2+ content and subsequently weaken systolic Ca 2+ 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.