Zhu Ning, Zhu Liuyan, Huang Bingwu, Xiang Wenjun, Zhao Xuyong
Department of Cardiology, The Third Affiliated Hospital of Shanghai University, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, China.
Department of General Practice, The Third Affiliated Hospital of Shanghai University, The Wenzhou Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, China.
Front Cardiovasc Med. 2022 Apr 26;9:868372. doi: 10.3389/fcvm.2022.868372. eCollection 2022.
Diabetic cardiomyopathy (DCM), characterized by cardiomyopathy with the absence of coronary artery disease, hypertension, and valvular heart disease in patients with diabetes, significantly increases the risk of heart failure. Galectin-3 (Gal-3) has been shown to regulate cardiac inflammation and fibrosis, but its role in DCM remains unclear. This study aimed to determine whether Gal-3 inhibition attenuates DCM and NF-κB p65 activation.
Diabetic cardiomyopathy (DCM) was established by intraperitoneal (IP) injection of streptozotocin for 5 consecutive days in mice. Myocardial injury markers, such as creatine kinase isoenzyme (CK-BM) and lactate dehydrogenase, were detected using ELISA. We used non-invasive transthoracic echocardiography to examine cardiac structure and function. Histological staining was used to explore myocardial morphology and fibrosis. Profibrotic markers and inflammatory cytokines were detected by ELISA and real-time PCR . The terminal deoxyribonucleotide transferasemediated dUTP nick end-labeling (TUNEL) and immunofluorescence assays were conducted to examine myocardial apoptosis and oxidative stress. Inflammatory cytokines induced by high glucose (HG) were also found in RAW264.7 macrophages. The underlying molecular mechanisms were determined using immunofluorescence and Western blotting analyses.
The Gal-3 knockdown was observed to ameliorate myocardial apoptosis, oxidative stress, inflammatory cytokines release, macrophage infiltration, and fibrosis, thus, decreasing cardiac dysfunction in DCM mice. In addition, the silence of Gal-3 could suppress macrophage infiltration and inflammatory cytokine release induced by HG. Finally, a Gal-3/NF-κB p65 regulatory network was clarified in the pathogenesis of DCM.
The Gal-3 may promote myocardial apoptosis, oxidative stress, inflammation, and fibrosis and by the mechanism of reduction of NF-κB p65 activation.
糖尿病性心肌病（DCM）的特征是糖尿病患者出现心肌病，且无冠状动脉疾病、高血压和瓣膜性心脏病，它会显著增加心力衰竭的风险。半乳糖凝集素-3（Gal-3）已被证明可调节心脏炎症和纤维化，但其在DCM中的作用仍不清楚。本研究旨在确定抑制Gal-3是否能减轻DCM和NF-κB p65的激活。
通过连续5天腹腔注射链脲佐菌素在小鼠中建立糖尿病性心肌病（DCM）模型。使用酶联免疫吸附测定法（ELISA）检测心肌损伤标志物，如肌酸激酶同工酶（CK-BM）和乳酸脱氢酶。我们使用非侵入性经胸超声心动图检查心脏结构和功能。组织学染色用于探究心肌形态和纤维化。通过ELISA和实时聚合酶链反应检测促纤维化标志物和炎性细胞因子。进行末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）和免疫荧光测定以检查心肌细胞凋亡和氧化应激。在RAW264.7巨噬细胞中也发现了高糖（HG）诱导的炎性细胞因子。使用免疫荧光和蛋白质印迹分析确定潜在的分子机制。
观察到Gal-３基因敲低可改善心肌细胞凋亡、氧化应激、炎性细胞因子释放、巨噬细胞浸润和纤维化，从而减轻DCM小鼠的心脏功能障碍。此外，Gal-３沉默可抑制HG诱导的巨噬细胞浸润和炎性细胞因子释放。最后，在DCM的发病机制中阐明了Gal-3/NF-κB p65调控网络。
Gal-3可能通过降低NF-κB p65激活促进心肌细胞凋亡、氧化应激、炎症和纤维化。
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