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目的探讨达格列净对糖尿病肾病的肾脏保护作用及其可能机制。方法收集糖尿病肾病患者118例,随机分为对照组和观察组,分别予以常规治疗和常规治疗+达格列净治疗12周。检测并比较治疗前后患者的血糖、糖化血红蛋白、尿白蛋白-肌酐比值、肾功能及血清基质金属蛋白酶组织抑制剂1(TIMP-1)、转化生长因子β1(TGF-β1)、单核细胞趋化因子1(MCP-1)、白介素6(IL-6)水平。结果治疗后,2组血糖、糖化血红蛋白、尿白蛋白-肌酐比值、TIMP-1、TGF-β1、MCP-1及IL-6较治疗前降低(P<0.05),且观察组上述指标的降低程度均大于对照组(P<0.05);观察组肾功能治疗后较治疗前下降(P <0.05),而对照组较治疗前无明显变化(P> 0.05)。结论达格列净能降低糖尿病肾病患者的尿蛋白水平,减缓肾损伤,具有肾脏保护作用,这可能与其下调肾脏致纤维化因子及炎性因子的表达有关。
Abstract：AIM To observe the protective effect and possible mechanism of dapagliflozin on early diabetic nephropathy. METHODS A total of 118 patients with diabetic nephropathy were randomly divided into observation group and control group, and they were given routine treatment and routine treatment combined with dapagliflozin for 12 weeks respectively. Blood glucose, glycosylated hemoglobin, urinary albumin-creatinine ratio, renal function and serum matrix tissue inhibitor of metalloproteinase1(TIMP-1), transforming growth factor β1(TGF-β1), monocyte chemotactic protein1(MCP-1) and interleukin 6(IL-6) were measured and compared before and after treatment. RESULTS After treatment, the blood glucose, glycosylated hemoglobin, urinary albumin-creatinine ratio, TIMP-1, TGF-β1, MCP-1 and IL-6 in 2 groups were all lower than those before treatment(P < 0.05), and the degree of reduction of the above indicators in the observation group was greater than that in the control group(P < 0.05); the renal function of the observation group decreased significantly after treatment compared with before treatment(P < 0.05), while the control group had no significant change compared with before treatment(P > 0.05). CONCLUSION Dapagliflozin can decrease proteinuria level, ameliorate kidney damage and protect the kidney in diabetic nephropathy patients, which may be related to slowing the expression of renal fibrotic and inflammatory factors.
[1]De NICOLA L,GABBAI F B,LIBERTI M E,et al.Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy:targeting the renal tubule in diabetes[J].Am J Kidney Dis,2014,64(1):16.
[2]KOWALSKI A,KRIKORIAN A,LERMA E V.Dyslipidemia in chronic kidney disease[J].Disease-a-Month,2015,61(9):396.
[3]TAGAWA A,YASUDA M,KUME S,et al.Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy[J].Diabetes,2016,65(3):755.
[4]GNUDI L,COWARD R J M,LONG D A.Diabetic nephropathy:perspective on novel molecular mechanisms[J].Trends Endocrinol Metab,2016,27(11):820.
[5] CHAN G C,TANG S C.Diabetic nephropathy:landmark clinical trials and tribulations[J].Nephrol Dial Transplant,2016,3 1(3):359.
[6]HA M,CHOI S Y,KIM M,et al.Diabetic nephropathy in type 2diabetic retinopathy requiring panretinal photocoagulation[J].Korean J Ophthalmol,2019,33(1):46.
[7] MA R,REN J M,LI P,et al.Activated YAP causes renal damage of type 2 diabetic nephropathy[J].Eur Rev Med Pharmacol Sci,2019,23(2):755.
[8]LIAO D,MA L,LIU J,et al.Cigarette smoking as a risk factor for diabetic nephropathy:a systematic review and meta-analysis of prospective cohort studies[J].PLoS One,2019,14(2):e0210213.
[9]VALLON V, PLATT K A,CUNARD R, et al.SGLT2 mediates glucose reabsorption in the early proximal tubule[J].J Am Soc Nephrol,2011,22(1):104.
[10]中华医学会糖尿病学分会.中国2型糖尿病防治指南[M].北京:北京大学医学出版社,2014.
[11]KOJIMA N, WILLIAMS J M,TAKAHASHI T,et al.Effects of a new SGLT2 inhibitor,luseogliflozin,on diabetic nephropathy in T2DN rats[J].J Pharmacol Exp Ther,2013,345(3):464.
[12]NAGATA T,FUKUZAWA T,TAKEDA M,et al.Tofogliflozin,a novel sodium-glucose co-transporter 2 inhibitor,improves renal and pancreatic function in db/db mice[J].Br J Pharmacol,2013,170(3):519.
[13]JIAN X,YANG Q L,XIAO S,et al.The effects of a sodiumglucose cotransporter 2 inhibitor on diabetic nephropathy and serum oxidized low-density lipoprotein levels[J].Eur Rev Med Pharmacol Sci,2018,22(12):3994.
[14]HEERSPINK H J,DESAI M,JARDINE M,et al.Canagliflozin slows progression of renal function decline independently of glycemic effects[J].J Am Soc Nephrol,2017,28(1):368.
[15]CAO T,XU R C,XU Y,et al.The protective effect of Cordycepin on diabetic nephropathy through autophagy induction in vivo and in vitro[J].Int Urol Nephrol,2019,51(10):1883.
[16]SHEN Y L,JIANG Y P,LI X Q,et al.ErHuang formula improves renal fibrosis in diabetic nephropathy rats by inhibiting CXCL6/JAK/STAT3 signaling pathway[J].Front Pharmacol,2020,10:1596.
[17]JOHN P,YADLA M.Noninvasive method of differentiating diabetic nephropathy and nondiabetic renal disease using serum bone morphogenetic protein-7 and transforming growth factor-beta1 levels in patients with type-2 diabetes mellitus[J].Saudi J Kidney Dis Transpl,2019,30(6):1300.
[18]CAKIRCA G,TURGUT F H.Serum matrix metalloproteinase-9,tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin complex levels in patients with early-stage diabetic nephropathy[J].Iran J Kidney Dis,2018,12(5):299.
[19]CZIROK S,FANG L,RADOVITS T,et al.Cinaciguat ameliorates glomerular damage by reducing ERK1/2 activity and TGF-βexpression in type-1 diabetic rats[J].Sci Rep,2017,7(1):11218.
[20]KUNDU A,RICHA S, DEY P, et al.Protective effect of EX-527against high-fat diet-induced diabetic nephropathy in Zucker rats[J].Toxicol Appl Pharmacol,2020,390:114899.
[21]ZABAD I E M, AMIN M N, EL-SHISHTAWY M M.Protective effect of vanillin on diabetic nephropathy by decreasing advanced glycation end products in rats[J].Life Sci,2019,239:117088.
[22]OMIDIAN M,MAHMOUDI M,JAVANBAKHT M H, et al.Effects of vitamin D supplementation on circulatory YKL-40 and MCP-1 biomarkers associated with vascular diabetic complications:a randomized,placebo-controlled,double-blind clinical trial[J].Diabetes Metab Syndr,2019,13(5):2873.
[23]KONDO M,TAHARA A,HAYASHI K,et al.Therapeutic effects of interleukin-1 receptor-associated kinase 4 inhibitor AS2444697on diabetic nephropathy in type 2 diabetic mice[J].Naunyn Schmiedebergs Arch Pharmacol,2020,393(7):1197.
[24]XIE C,WU W,TANG A,et al.lncRNA GAS5/miR-452-5p reduces oxidative stress and pyroptosis of high-glucose-stimulated renal tubular cells[J].Diabetes Metab Syndr Obes,2019,12:2609.
基本信息:
DOI：10.19577/j.1007-4406.2021.05.003
中图分类号:R587.2;R692.9
引用信息:
[1]付强,刘丽秋.达格列净对早期糖尿病肾病的保护作用及其可能机制[J].中国临床药学杂志,2021,30(05):330-334.DOI:10.19577/j.1007-4406.2021.05.003.
基金信息:
山东省自然科学基金(编号R2010HM055)
2021-09-25
2021-09-25