Wang Jing, Wang Ru, Li Jiali, Yao Zhuhua
Department of Cardiology, Tianjin Union Medical Center, Tianjin 300121, P.R. China.
Exp Ther Med. 2021 Sep;22(3):944. doi: 10.3892/etm.2021.10376. Epub 2021 Jul 1.
Diabetic cardiomyopathy is a common complication of diabetes, in which endoplasmic reticulum stress (ERS) serves an important role. Rutin can treat the myocardial dysfunction of diabetic rats. However, to the best of our knowledge, studies on the effects of Rutin on myocardial injury caused by diabetes from the perspective of ERS have not previously been reported. In the present study, the role of rutin in the regulation of ERS in myocardial injury was assessed. Different high glucose concentrations were used to treat H9C2 myoblast cells to establish a myocardial damage model. A cell counting kit-8 assay was used to determine cell viability. A lactate dehydrogenase kit was used to detect cytotoxicity. Apoptosis levels were determined using a TUNEL assay. Western blotting was used to determine the expression levels of apoptosis-related proteins and ERS-related proteins, including heat shock protein A family member 5, inositol-requiring enzyme-1α, X-box binding protein 1, activating transcription factor 6, C/EBP-homologous protein (CHOP), cleaved caspase-12 and caspase-12. The anti-apoptotic and anti-ERS effects of Rutin on H9C2 cardiac cells induced by high glucose were examined after the administration of the ERS activator thapsigargin (TG). The results indicated that rutin could dose-dependently inhibit the level of apoptosis and ERS induced by high glucose in H9C2 cells. After administration of the ERS activator TG, it was demonstrated that TG could reverse the anti-apoptotic and anti-ERS effects of rutin on H9C2 cells stimulated with high glucose. Collectively, the present results suggested that rutin may alleviate cardiomyocyte model cell injury induced by high glucose through the inhibition of apoptosis and ERS.
糖尿病性心肌病是糖尿病常见的并发症，其中内质网应激（ERS）起重要作用。芦丁可治疗糖尿病大鼠的心肌功能障碍。然而，据我们所知，以前尚未有从ERS角度研究芦丁对糖尿病所致心肌损伤影响的报道。在本研究中，评估了芦丁在心肌损伤中对ERS的调节作用。使用不同的高糖浓度处理H9C2成肌细胞以建立心肌损伤模型。采用细胞计数试剂盒-8法测定细胞活力。使用乳酸脱氢酶试剂盒检测细胞毒性。采用TUNEL法测定凋亡水平。通过蛋白质印迹法测定凋亡相关蛋白和ERS相关蛋白的表达水平，包括热休克蛋白A家族成员5、肌醇需求酶-1α、X盒结合蛋白1、活化转录因子6、C/EBP同源蛋白（CHOP）、裂解的半胱天冬酶-12和半胱天冬酶-12。在给予ERS激活剂毒胡萝卜素（TG）后，检测芦丁对高糖诱导的H9C2心肌细胞的抗凋亡和抗ERS作用。结果表明，芦丁可剂量依赖性地抑制高糖诱导的H9C2细胞凋亡水平和ERS。给予ERS激活剂TG后，证明TG可逆转芦丁对高糖刺激的H9C2细胞的抗凋亡和抗ERS作用。总体而言，本研究结果表明，芦丁可能通过抑制凋亡和ERS来减轻高糖诱导的心肌细胞模型损伤。
