陈彦平,张金苹
CHEN Yanping,ZHANG Jinping

• 1:北京市门头沟区中医医院内分泌科
• 2:中日友好医院内分泌科

摘要(Abstract)：

目的:探究循环miRNA-26a水平对沙格列汀治疗糖尿病伴非酒精性脂肪肝(NAFLD)疗效的影响。方法:113例2型糖尿病伴NAFLD患者,采用沙格列汀治疗6个月;以患者治疗1 d时的血清miR-26a相对表达中位数为临界值,将患者分为miR-26a高表达组(n=49)及miR-26a低表达组(n=64);比较两组患者治疗前及治疗6个月时的空腹血糖(FPG)、餐后2 h血糖(2hPPG)、糖化血红蛋白(Hb A1c)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、γ-谷氨酰转肽酶(GGT)、总胆固醇(TC)及甘油三酯(TG)水平;比较沙格列汀对两组患者NAFLD的治疗效果。结果:治疗前两组患者血清FPG、2hPPG、HBA1c、ALT、AST、GGT、TC及TG水平比较,差异无统计学意义(P> 0. 05);治疗后两组患者血清FPG、2hPPG、HBA1c、ALT、AST、GGT、TC及TG水平均较治疗前显著降低(P <0. 05),但治疗后两组患者血清FPG、2hPPG、HBA1c、ALT、AST、GGT、TC及TG水平比较,差异无统计学意义(P> 0. 05); 113例患者治疗NAFLD的总有效率为73. 5%,miR-26a高表达组治疗NAFLD的总有效率显著高于miR-26a低表达组,差异有统计学意义(P <0. 05)。结论:高miR-26a表达的糖尿病伴NAFLD患者对沙格列汀治疗的敏感性更高。
Objective: To investigate the effect of circulating miRNA-26 a on the efficacy of saxagliptin in the treatment of patients with type 2 diabetes mellitus( T2 D) complicated with non-alcoholic fatty liver disease( NAFLD). Methods: A total of 113 T2 D patients complicated with NAFLD admitted to the Mentougou district traditional Chinese medicine hospital hospital from January 2015 to December2017 were selected as the study subjects and treated with saxagliptin for 6 months. Based on the median relative expression of serum miR-26 a as a critical value,patients were divided into miR-26 a high expression group( n = 49) and low expression group( n = 64). The improvement of blood glucose,liver function and blood lipid level before/after treatment and the therapeutic effect of NAFLD were compared in the two groups. Results: The blood glucose levels in both groups had no significant difference( P > 0. 05),but the treatment remarkably decreased blood glucose levels in both groups( P < 0. 05).Interestingly,the patients with high expression of miR-26 a had more significant reduction in ALT,AST,GGT,TC and TG( P < 0. 05). The total effective rate of miR-26 a high expression group was83. 7%,while the total effective rate of low expression group was 65. 6%,the difference was statistically significant( P < 0. 05). Conclusion: Monitoring serum miR-26 a expression may provide the basis for the evaluation of the therapeutic effect of saxagliptin on T2 D patients complicated NAFLD.

关键词(KeyWords)： 微小RNA;miR-26a;糖尿病;酒精性脂肪肝;肝功能;血糖;血脂
micro RNA;miR-26a;diabetes;alcoholic fatty liver disease;liver function;blood glucose;blood fat

Abstract:

Keywords:

基金项目(Foundation): 北京市科学技术委员会基金资助项目(2017YKSJ04)

作者(Author): 陈彦平,张金苹
CHEN Yanping,ZHANG Jinping

DOI: 10.19367/j.cnki.1000-2707.2019.02.023

参考文献(References)：

• [1] SU Q,KUMAR V,SUD N,et al. MicroRNAs in thepathogenesis and treatment of progressive liver injury inNAFLD and liver fibrosis[J]. Adv Drug Deliv Rev,2018,3(3):159-165.
• [2]CHALASANI N,YOUNOSSI Z,LAVINE J E,et al. Thediagnosis and management of non-alcoholic fatty liver dis-ease:practice Guideline by the American Association forthe Study of Liver Diseases,American College of Gastro-enterology,and the American Gastroenterological Associ-ation[J]. Hepatology,2012,55(6):2005-2023.
• [3]WILLIAMS C D,STENGEL J,ASIKE M I,et al. Preva-lence of nonalcoholic fatty liver disease and nonalcoholicsteatohepatitis among a largely middle-aged population u-tilizing ultrasound and liver biopsy:a prospective study[J]. Gastroenterology,2011,140(1):124-131.
• [4] YAMADA H,SUZUKI K,ICHINO N,et al. Associa-tions between circulating microRNAs(miR-21,miR-34a,miR-122 and miR-451)and non-alcoholic fatty liver[J].Clin Chim Acta,2013,424:99-103.
• [5] CERMELLI S,RUGGIERI A,MARRERO J A,et al.Circulating microRNAs in patients with chronic hepatitisC and non-alcoholic fatty liver disease[J]. PLo S One,2011,6(8):e23937.
• [6]LIU Y,ZHANG Z,CHEN R,et al. Therapeutic effect ofsaxagliptin in rat models of nonalcoholic fatty liver andtype 2 diabetes[J]. Nan Fang Yi Ke Da Xue Xue Bao,2014,34(6):862-868.
• [7]MALMSTROM H,WALLDIUS G,CARLSSON S,et al.Elevations of metabolic risk factors 20 years or more be-fore diagnosis of type 2 diabetes-experience from theAMORIS study[J]. Diabetes Obes Metab,2018,8(7):e24937.
• [8]KAMADA Y,ONO M,HYOGO H,et al. Use of Mac-2binding protein as a biomarker for nonalcoholic fatty liverdisease diagnosis[J]. Hepatol Commun,2017,1(8):780-791.
• [9]WONG C M,TSANG F H,NG I O. Non-coding RNAs inhepatocellular carcinoma:molecular functions and patho-logical implications[J]. Nat Rev Gastroenterol Hepatol,2018,33(15):1500-1510.
• [10]WU Y L,ZHU Y B,HUANG R D,et al. Multiple Mi-croRNAs ameliorate hepatocyte steatosis and injury bysuppressing FABP1 expression[J]. Cell Physiol Bio-chem,2017,44(6):2243-2255.
• [11]ZHUGE B,LI G. MiR-150 deficiency ameliorated hepa-tosteatosis and insulin resistance in nonalcoholic fatty liv-er disease via targeting CASP8 and FADD-like apoptosisregulator[J]. Biochem Biophys Res Commun,2017,494(3-4):687-692.
• [12]DRUCKER D J. The biology of incretin hormones[J].Cell Metab,2006,3(3):153-165.
• [13]SHIRAKAWA J,FUJII H,OHNUMA K,et al. Diet-in-duced adipose tissue inflammation and liver steatosis areprevented by DPP-4 inhibition in diabetic mice[J]. Dia-betes,2011,60(4):1246-1257.
• [14]ZHENG L,LIN S,LV C. MiR-26a-5p regulates cardiacfibroblasts collagen expression by targeting ULK1[J].Sci Rep,2018,8(1):2104.
• [15]WANG H,LUO J,ZHANG T,et al. MicroRNA-26a/band their host genes synergistically regulate triacylglycerolsynthesis by targeting the INSIG1 gene[J]. RNA Biol,2016,13(5):500-510.

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