Quercetin ameliorates myocardial injury in diabetic rats by regulating L-type calcium channels

doi:10.12122/j.issn.1673-4254.2025.03.11

Abstract

Abstract:

Objective To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. Methods Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. Results The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. Conclusion Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.

Key words: quercetin, diabetic cardiomyopathy, L-type calcium currents, cuproptosis

Hongyan SUN, Guoqing LU, Chengwen FU, Mengwen XU, Xiaoyi ZHU, Guoquan XING, Leqiang LIU, Yufei KE, Lemei CUI, Ruiyang CHEN, Lei WANG, Pinfang KANG, Bi TANG. Quercetin ameliorates myocardial injury in diabetic rats by regulating L-type calcium channels[J]. Journal of Southern Medical University, 2025, 45(3): 531-541.

Figures/Tables 6

Fig.1 Effect of quercetin on blood glucose (A) and weight (B) in diabetic rats (Mean±SD, n=6). **P<0.01 vs Con, ##P<0.01 vs DM.

Fig.2 Effect of quercetin on cardiac function in diabetic rats. A: Comparison of echocardiographic findings in each group. B-G: LVEF%, LVFS%, LVEDD, LVESD, CO and HR of SD rats in each group. Data are presented as Mean±SD (n=6), **P<0.01 vs Con; #P<0.05, ##P<0.01 vs DM.

Fig.3 Effect of quercetin on myocardial structure in diabetic rats. A: HE, Sirius Red, and WGA staining results of SD rats in each group. B: Analysis of the results of Sirius Red staining in each group. C: Analysis of WGA staining in each group. Data are presented as Mean±SD (n=3). **P<0.01 vs Con, #P<0.05, ##P<0.01 vs DM.

Fig.4 Effect of quercetin on myocardial FDX1 expression and serum copper level in diabetic rats. A: Immunohistochemical staining of FDX1. B: Quantitative analysis of FDX1 expression levels; C: Serum Cu levels in each group. D, E: FDX1 protein expression levels of SD rats in different groups detected by Western blotting. Data are presented as Mean±SD (n=3). **P<0.01 vs Con; #P<0.05, ##P<0.01 vs DM; △P<0.05, △△P<0.01 vs DM+Empa.

Fig.5 Effect of quercetin on high glucose-induced injury in rat H9C2 cardiomyocytes. A, B: FDX1 protein expression levels of FDX1 protein in each group detected by Westernblotting. C, D: FDX1 expression levels in each group detected by immunofluorescence assay. E, F: CK-MB and LDH levels in each group. Data are presented as Mean±SD (n=3). **P<0.01 vs Con; #P<0.05, ##P<0.01 vs HG.

Fig.6 Effects of quercetin on myocardial ICa-L and action potentials (AP) in diabetic rats. A: Representative recording traces ICa-L currents in different groups. B: Current-voltage relationship of ICa-L currents in different groups. C: Representative action potentials (AP) in APD60 and APD90 repolarization and APA recorded in different groups. D, E: APDs and APA in different groups. Data are presented as Mean±SD (n=12), *P<0.05, **P<0.01 vs Con, #P<0.05, ##P<0.01 vs DM, △P<0.05 vs DM+Empa.

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