卡格列净对2型糖尿病患者肾功能、血清微RNA-126和微RNA-101表达的影响及临床意义

Effect and clinical significance of canagliflozin on renal function and expressions of serum miRNA-126 and miRNA-101 in patients with type 2 diabetes mellitus

目的探讨卡格列净对2型糖尿(T2DM)患者肾功能、血清微RNA(miRNA)-126和miRNA-101表达的影响及临床意义。方法选取2017年9月至2019年12月长治医学院附属和济医院收治的408例T2DM患者作为研究对象,分为对照组(200例)和研究组(208例)。两组均给予饮食运动干预及胰岛素等常规治疗,对照组患者在常规治疗基础上给予安慰剂,研究组患者则在常规治疗基础上给予卡格列净治疗,两组患者均采用糖尿病饮食、运动锻炼、调整作息、血糖监测、糖尿病健康宣教等基础干预,并根据血糖监测结果,调整皮下注射门冬胰岛素30剂量。采用实时荧光定量聚合酶链反应(RT-qPCR)检测不同组别患者血清miRNA-126和miRNA-101表达水平,用药4周后评价对患者的治疗效果。结果对照组治疗后空腹血糖(FPG)、餐后2 h血糖(2 h PBG)、糖化血红蛋白(HbA1c)较治疗前降低(P<0.05),但24 h尿蛋白定量(24 h Upr)、尿白蛋白/肌酐比值(UACR)、肾小球滤过率(eGFR)及血清miRNA-126和miRNA-101表达水平无明显变化(P>0.05)。研究组治疗后FPG、2 h PBG、HbA1c及24 h Upr、UACR及血清miRNA-101表达水平较治疗前显著降低(P<0.05),eGFR及miRNA-126表达水平较治疗前显著升高(P<0.05)。与对照组比较,研究组治疗后FPG、2 h PBG、HbA1c、24 h Upr、UACR及血清miRNA-101表达水平显著降低(P<0.05);eGFR及miRNA-126表达水平显著升高(P<0.05)。研究总有效率明显高于对照组(85.10%比28.50%,P<0.05),不良事件总发生率显著低于对照组(8.18%比34.50%,P<0.05)。结论卡格列净不仅能改善T2DM患者糖代谢,还能发挥肾保护作用,其作用机制可能与调节血清miRNA-126和miRNA-101的表达水平有关。

Objective To explore the effect and clinical significance of canagliflozin on the renal function and expressions of serum miRNA-126 and miRNA-101 in patients with type 2 diabetes mellitus(T2DM).Methods 408 patients with T2DM who were admitted to Heji Hospital Affiliated to Changzhi Medical College from September 2017 to December 2019 were selected as the research subjects,and they were divided into control group(200 cases)and study group(208 cases).Both groups were given routine treatment methods such as diet and exercise intervention and insulin,and patients in the control group were given placebo on the basis of routine treatment,and patients in the study group were treated with canagliflozin based on routine treatment.Patients in both groups were given diabetic diet,exercise,adjustment of work and rest,blood glucose monitoring,diabetes health education and other basic interventions,and dose of subcutaneous insulin aspart 30 were adjusted according to the results of blood glucose monitoring.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression levels of serum miRNA-126 and miRNA-101 in different groups,and the therapeutic effect was evaluated after 4 weeks of medication.Results After treatment,the expression levels of fasting plasma glucose(FPG),2 h postprandial blood glucose(2 h PBG),glycosylated hemoglobin(HbA1c),24-hour urinary protein quantification(24 h Upr),urinary albumin/creatinine ratio(UACR)and serum miRNA-101 in study group were significantly decreased compared with those before treatment(P<0.05)while the expression levels of eGFR and miRNA-126 after treatment were significantly enhanced compared to before treatment(P<0.05).After treatment,FBG,PBG and HbA1c in control group were declined compared with those before treatment(P<0.05),but there were no significant changes in 24 h Upr,UACR,estimated glomerular filtration rate(eGFR)and serum miRNA-126 and miRNA-101 in control group before and after treatment(P>0.05).The expression levels of FBG,PBG,HbA1c,24 h Upr,UACR and serum miRNA-101 in study group after treatment were significantly lower than those in control group(P<0.05)while the expression levels of eGFR and miRNA-126 were higher than those in control group(P<0.05).The total effective rate in study group was 85.10%,which was significantly higher than 28.50%in control group(P<0.05).The total incidence rate of adverse events in study group was significantly lower than that in control group(8.18%vs 34.50%)(P<0.05).Conclusion Canagliflozin can not only improve the glucose metabolism in patients with T2DM,but also play a protective role in kidney,and its role mechanism may be related to the regulations of expression levels of serum miRNA-126 and miRNA-101.