达格列净对2型糖尿病合并慢性心力衰竭患者微小RNA-423-5p的调控作用及心功能的影响研究

Effects of Dapagliflozin on the Expression of MicroRNA-423-5p and Cardiac Function in Patients with Type 2 Diabetes Mellitus and Chronic Heart Failure

背景糖尿病合并心力衰竭的患者数量庞大,达格列净作为新型降糖药物,目前已被指南推荐用于心力衰竭的治疗,但其改善心功能的作用机制还未完全明确。目的研究达格列净对2型糖尿病(T2DM)合并慢性心力衰竭(CHF)患者血浆微小RNA-423-5p(miRNA-423-5p)表达的影响及其与心功能之间的相关性。方法纳入2021-04-01至2021-11-30就诊于解放军第九六〇医院的T2DM合并CHF患者50例为研究对象,分为达格列净组(n=25)和对照组(n=25),达格列净组给予达格列净10 mg/d,对照组给予其他降糖药物,余治疗原则相同,治疗6个月。另纳入同一时期于本院健康体检的心功能正常者为健康人群组(n=25)。通过数字病历系统收集患者的基本资料,包括年龄、性别、吸烟史、高血压史、血压水平、体质指数(BMI)、血脂、血糖、肌酐(Cr)、氨基末端脑钠肽前体(NT-proBNP)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、纽约心脏病协会(NYHA)心功能分级、心脏彩超、合并用药情况,并留取血液标本进行miRNA-423-5p的检测。治疗4周进行门诊随访,收集患者心功能指标及miRNA-423-5p的结果。治疗6个月进行门诊随访,收集患者心功能指标、血压水平、ALT、AST、Cr。采用Pearson相关分析或Spearman秩相关分析探究miRNA-423-5p表达水平与患者心功能指标的相关性。结果干预6个月达格列净组患者左心室射血分数(LVEF)、每搏输出量(SV)、左心室短轴缩短率(LVFS)高于对照组,左心室舒张末期内径(LVEDD)低于对照组(P<0.05);两组干预4周、干预6个月LVEDD较同组干预前降低,LVEF、SV、LVFS较同组干预前升高(P<0.05)。干预4周达格列净组NT-proBNP、miRNA-423-5p水平低于对照组(P<0.05),两组干预后NT-proBNP、miRNA-423-5p水平较同组干预前降低(P<0.05)。相关性分析结果显示,干预4周血浆miRNA-423-5p表达水平与NT-proBNP水平呈正相关(r_(s)=0.609,P<0.05),与LVEF水平呈负相关(r=-0.406,P<0.05)。结论达格列净可改善T2DM合并CHF患者的心功能,降低NT-proBNP及LVEDD,提高LVEF、SV、LVFS,其作用机制可能与调控血浆miRNA-423-5p表达水平有关。

Background There are numerous patients with diabetes complicated with heart failure. Dapagliflozin is a new hypoglycemic drug that has been used for heart failure according to guideline recommendation,however,its mechanism of improving heart function has not been fully defined. Objective To study the effects of dapagliflozin on the expression of plasma miRNA-423-5p and cardiac function in patients with type 2 diabetes mellitus(T2DM) and chronic heart failure(CHF).Methods Fifty patients with T2DM complicated with CHF admitted to the 960th Hospital of PLA from April 1 to November 30,2021 were enrolled and randomly divided into dapagliflozin group(n=25)and control group(n=25). Both groups received the same treatment for six months except that dapagliflozin group received dapagliflozin 10 mg/d per day,and the control group received other hypoglycemic drugs. They were compared to healthy physical examinees with normal cardiac function(healthy group,n=25). Basic data of the patients were collected through the electronic medical record system,including age,sex,smoking history,hypertension,blood pressure level,body mass index(BMI),blood lipid,blood glucose,creatinine(Cr),amino-terminal pro-B-type natriuretic peptide precursor(NT-proBNP),alanine aminotransferase(ALT),aspartate aminotransferase(AST),NYHA class,results of cardiac color ultrasound and drug combination. Blood samples were collected for the detection of miRNA-423-5p. A six-month follow-up was given to the patients with the time of first administration of dapagliflozin after inclusion as the starting point,during which patients’ cardiac function indices and miRNA-423-5p were measured and collected at the end of four weeks of treatment,and their cardiac function indices,blood pressure level,ALT,AST,and Cr were measured at six months of treatment. Pearson correlation analysis or Spearman rank correlation analysis was used to analyze the correlation between miRNA-423-5p expression level and cardiac function indices of the patients. Results After 6 months of intervention, left ventricular ejection fraction(LVEF),stroke output(SV)and left ventricular short-axis shortening rate(LVFS)in daglizin group were higher than those in control group,while left ventricular end-diastolic diameter(LVEDD)was lower than those in control group(P<0.05). After 4 weeks and 6 months of intervention,LVEDD in 2 groups was lower than before intervention,while LVEF,SV and LVFS in 2 groups were higher than before intervention(P<0.05).After 4 weeks of intervention, the level of NT-proBNP and miRNA-423-5p in Dagliegine group was lower than that in control group(P<0.05),the level of NT-proBNP and miRNA-423-5p in two groups after intervention was lower than that before intervention in the same group(P<0.05). The results of correlation analysis showed that the expression level of miRNA-423-5p was positively correlated with the level of NT-proBNP(r_(s)=0.609,P<0.05),and negatively correlated with the level of LVEF(r=-0.406,P<0.05). Conclusion Dapagliflozin could improve cardiac function,reduce the levels of NT-proBNP and LVEDD,and increase the levels of LVEF,SV and LVFS in patients with T2DM and CHF,and the mechanism of action may be related to its regulation of the expression of plasma miRNA-423-5p.