达格列净联合西格列汀对老年糖尿病肾脏疾病患者肾功能及外周血清核苷酸结合寡聚化结构域样受体蛋白3炎性小体影响的研究

Effect of Dapagliflozin combined with Sitagliptin on renal function and nucleotide-binding oligomeric domain-like receptor protein 3 inflammasome in peripheral serum in patients with elderly diabetic kidney disease

目的探讨达格列净联合西格列汀对老年DKD患者肾功能及外周血清核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体的影响。方法选取2021年8月至2022年6月于徐州医科大学附属医院老年医学科及内分泌科住院治疗的老年DKD患者120例,随机分为达格列净组(Dap)、西格列汀组(Sit)和联合治疗组(Com),每组各40例,各组在基础降糖治疗上分别加用达格列净、西格列汀、两药联合治疗,疗程12周,观察各组治疗前后糖代谢指标、肾功能相关指标及NLRP3炎性小体水平。结果各组治疗后FPG、2 hPG、HbA1c、UACR、血尿酸(SUA)、胱抑素C(CysC)、血尿素(UREA)、NLRP3低于治疗前(P<0.05)。治疗后Dap、Com组血肌酐(Scr)低于治疗前(P<0.05),eGFR高于治疗前(P<0.05)。Com组FPG、2 hPG、HbA1c、UACR、CysC、UREA、NLRP3低于Dap、Sit组(P<0.05)。Spearman相关分析显示,NLRP3炎性小体与治疗前DM病程、FPG、2 hPG、HbA1c、Scr、SUA、UREA、CysC、UACR呈正相关(P<0.05),与eGFR呈负相关(P<0.05)。多元线性回归分析显示,FPG、SUA是NLRP3炎性小体的影响因素。结论达格列净联合西格列汀可减少老年DKD患者血清NLRP3炎性小体,延缓肾功能恶化,且抗炎效果达格列净优于西格列汀,二者联合治疗优于单药治疗。

Objective To explore the effect of Dapagliflozin combined with Sitagliptin on renal function and the expression of peripheral serum nucleotide-binding oligomeric domain-like receptor protein 3(NLRP3)inflammasome in patients with elderly diabetic kidney disease(DKD),as well as the influencing factors for NLRP3 inflammasome and its correlation with renal function.Methods A total of 120 elderly hospitalized patients with DKD were enrolled in this study from the Department of Geriatrics and Endocrinology,Affiliated Hospital of Xuzhou Medical University from August 2021 to June 2022.All the participants were divided into dapagliflozin group(Dap),Sitagliptin group(Sit)and combined treatment group(Com),with 40 cases in each group.Participants in each group was additionally treated with Dapagliflozin,Sitagliptin or combination of two drugs on their current hypoglycemia treatment,respectively,and followed up for 12 weeks.Glucose metabolism indexes,renal function related indexes and NLRP3 inflammasome levels were evaluatedat baseline and after treatment.Results After treatment,FPG,2 hPG,HbA_1c,UACR,CysC,SUA,UREA and NLRP3 inflammasome were lower in all groups than baseline(P<0.05).The Scr was lower and eGFR was higher than baseline in Dap and Com groups(P<0.05).FPG,2 hPG,HbA_1c,UACR,CysC,UREA and NLRP3 inflammasome were lowerin Com group than in Dap and Sit group(P<0.05).Spearman correlation analysis showed that NLRP3 inflammasomes were positively correlated with the DM duration,FPG,2 h PG,HbA_1c,Scr,SUA,UREA,CysC and UACR(P<0.05),and negatively correlated with eGFR(P<0.05).Multiple linear regression analysis showed that FPG and SUA were the influencing factors for serum NLRP3inflammasome.Conclusion Dapagliflozin combined with Sitagliptin can reduce the levels of serum NLRP3 inflammasome,delay the deterioration of renal function.The anti-inflammatory effect of Dapagliflozin is better than sitagliptin,and the dual combination treatment was better than monotherapy.