Lin Na, Lin Hui, Yang Qi, Lu Wenqiang, Sun Zhenzhu, Sun Shimin, Meng Liping, Chi Jufang, Guo Hangyuan
Department of Cardiology, Shaoxing People's Hospital (Shaoxing Hospital, Zhejiang University School of Medicine), Shaoxing, China.
Department of Cardiology, The First Clinical Medical College, Wenzhou Medical University, Wenzhou, China.
Front Pharmacol. 2021 Jan 12;11:598353. doi: 10.3389/fphar.2020.598353. eCollection 2020.
Recent studies have revealed that a novel selective sodium-glucose cotransporter 1 (SGLT1) inhibiton has shown beneficial effects in cardiovascular diseases. However, the question of whether SGLT1 inhibition influences diabetic cardiomyopathy (DCM) remains unanswered. In this study, we investigated the influence and underlying mechanism of SGLTI inhibition on DCM. SGLT1 levels were measured in diabetic patients with similar conditions who visited our hospital from January to December 2019. Wistar male rats (n = 50) were divided into five groups: control, diabetes induced by streptozotocin infusion, and diabetes treated with 0.5, 1.0, or 1.5 mg/kg mizagliflozin via stomach gavage for 12 weeks. H9C2 cardiomyocytes were treated with mizagliflozin and then exposed to a high glucose concentration (30 mmol/L). TUNEL assays were performed, and bcl2, bax, p-p38, p-Erk, p-JNK and caspase-3 levels were measured. We used siRNA and an SGLT1 overexpression plasmid to detect the effects of SGLT1. SGLT1 levels were significantly elevated in DCM patients, and receiver operating characteristic (ROC) curve analysis identified SGLT1 as influencing DCM. The area under the curve (AUC) was 0.705 ( < 0.05), with 65.8% sensitivity, and 62.2% specificity. SGLT1 inhibition appeared to attenuate apoptosis in DCM via the JNK and p38 pathway. SGLT1 can be used as a marker for the diagnosis of DCM, and SGLT1 inhibition can attenuate apoptosis, thereby suppressing DCM development via the JNK and p38 pathway.
最近的研究表明，一种新型选择性钠-葡萄糖协同转运蛋白1（SGLT1）抑制剂在心血管疾病中显示出有益作用。然而，SGLT1抑制是否影响糖尿病性心肌病（DCM）的问题仍未得到解答。在本研究中，我们调查了SGLT1抑制对DCM的影响及其潜在机制。对2019年1月至12月来我院就诊的病情相似的糖尿病患者测量SGLT1水平。将50只雄性Wistar大鼠分为五组：对照组、链脲佐菌素诱导糖尿病组，以及通过胃管饲法用0.5、1.0或1.5mg/kg米格列净治疗糖尿病12周的组。用米格列净处理H9C2心肌细胞，然后将其暴露于高葡萄糖浓度（30mmol/L）下。进行TUNEL检测，并测量bcl2、bax、p-p38、p-Erk、p-JNK和caspase-3水平。我们使用小干扰RNA（siRNA）和SGLT1过表达质粒来检测SGLT1的作用。DCM患者的SGLT1水平显著升高，受试者工作特征（ROC）曲线分析确定SGLT1对DCM有影响。曲线下面积（AUC）为0.705（P<0.05），灵敏度为65.8%，特异性为62.2%。SGLT1抑制似乎通过JNK和p38途径减轻DCM中的细胞凋亡。SGLT1可作为DCM诊断的标志物，SGLT1抑制可减轻细胞凋亡，从而通过JNK和p38途径抑制DCM的发展。
