2型糖尿病足溃疡患者血清Toll样受体9与25羟维生素D的关系
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摘要
目的探讨T2DM糖尿病足溃疡(DFU)患者血清Toll样受体9(TLR9)与25羟维生素D[25(OH)D]的关系。方法选取2017年10月至2018年5月我院门诊内分泌科就诊的T2DM患者80例,其中,并发DFU患者40例(DFU组),无DF患者40例(T2DM组)。同期随机筛选健康体检者50名为正常对照(NC)组。ELISA测定血清TLR9水平,电化学发光法测定25(OH)D水平。结果与T2DM组、NC组比较,DFU组血清TLR9水平升高,25(OH)D水平降低(P<0. 05)。Pearson相关分析显示,血清TLR9水平与HbAlc、TG、LDL-C、FIns、HOMA-IR呈正相关(P<0. 05),与25(OH)D呈负相关(P<0. 05)。Logistic回归分析显示,HbA1c、HOMA-IR、TG、LDL-C、TLR9、25(OH)D为T2DM患者发生DFU的影响因素。结论 DFU患者血清TLR9水平升高及25(OH)D水平降低,可能共同参与了DFU的发生发展。
Objective To investigate the relationship between serum Toll-like receptors 9(TLR9 and 25-hydroxy vitamin D(25-hydroxy vitamin D,25(OH)D)in patients with type 2 diabetes foot ulcer(DFU).MethodsA total of 80 patients with type 2 diabetes mellitus(T2 DM)were selected from our outpatient department of endocrinology during October 2017 to May 2018,and divided into two groups:patients without diabetic foot(T2 DM group,n=40)and patients with diabetic foot ulcer(DFU group,n=40). At the same time,healthy subjects in the health examination center were randomly selected as the normal control(NC group,n=50). The serum level of TLR9 was determined by ELISA,and 25(OH)D was tested by electrochemiluminescence.ResultsSerum TLR9 level was higher[(42. 33 ± 2. 80)vs(35. 81±3. 20)vs(20. 56±3. 60)μg/L,P<0. 05],while 25(OH)D level was lower[(9. 78±2. 52)vs(14. 31±3. 30)vs(27. 67±3. 47)ng/ml,P<0. 05]in DFU group than in T2 DM group and NC group(P<0. 05). Pearson correlation analysis showed that serum TLR9 level was negatively correlated with 25(OH)D(P<0. 05),and positively correlated with HbAlc,TG,LDL-C,FIns and HOMA-IR(P<0. 05). Logistic regression analysis showed that HbA1 c,HOMA-IR,TG,LDL-C,TLR9,25(OH)D were risk factors for DFU.ConclusionThe increase of TLR9 level and the decrease of 25(OH)D level in serum may be involved in the occurrence and development of DFU.
Objective To investigate the relationship between serum Toll-like receptors 9(TLR9 and 25-hydroxy vitamin D(25-hydroxy vitamin D,25(OH)D)in patients with type 2 diabetes foot ulcer(DFU).MethodsA total of 80 patients with type 2 diabetes mellitus(T2 DM)were selected from our outpatient department of endocrinology during October 2017 to May 2018,and divided into two groups:patients without diabetic foot(T2 DM group,n=40)and patients with diabetic foot ulcer(DFU group,n=40). At the same time,healthy subjects in the health examination center were randomly selected as the normal control(NC group,n=50). The serum level of TLR9 was determined by ELISA,and 25(OH)D was tested by electrochemiluminescence.ResultsSerum TLR9 level was higher[(42. 33 ± 2. 80)vs(35. 81±3. 20)vs(20. 56±3. 60)μg/L,P<0. 05],while 25(OH)D level was lower[(9. 78±2. 52)vs(14. 31±3. 30)vs(27. 67±3. 47)ng/ml,P<0. 05]in DFU group than in T2 DM group and NC group(P<0. 05). Pearson correlation analysis showed that serum TLR9 level was negatively correlated with 25(OH)D(P<0. 05),and positively correlated with HbAlc,TG,LDL-C,FIns and HOMA-IR(P<0. 05). Logistic regression analysis showed that HbA1 c,HOMA-IR,TG,LDL-C,TLR9,25(OH)D were risk factors for DFU.ConclusionThe increase of TLR9 level and the decrease of 25(OH)D level in serum may be involved in the occurrence and development of DFU.
引文
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[10]Oliveira CD,Biddulph JP,Hirani V,et al.Vitamin D and inflammatory markers:cross-sectional analyses using data from the English longitudinal study of ageing(ELSA).J Nutr Sci,2017,6:e1.
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[13]Gu JQ,Wang DF,Yan G,et al.A Toll-like receptor 9-mediated pathway stimulates perilipin 3(TIP47)expression and induces lipid accumulation in macrophages.Am J Physiol Endocrinol Metab,2010,299:E593-E600.
[14]Ye L,Feng Z,Doycheva D,et al.CpG-ODN exerts a neuroprotective effect via the TLR9/pAMPK signaling pathway by activation of autophagy in a neonatal HIE rat model.Exp Neurol,2017,301:70-80.
[15]Singh K,Agrawal NK,Gupta SK,et al.Increased expression of TLR9 associated with pro-inflammatory S100A8 and IL-8 in diabetic wounds could lead to unresolved inflammation in type 2 diabetes mellitus(T2DM)cases with impaired wound healing.J Diabetes Complications,2016,30:99-108.
[16]Narumi K,Miyakawa R,Ueda R,et al.Proinflammatory proteins S100A8/S100A9 activate NK cells via interaction with RAGE.JImmunol,2015,194:5539-5548.
[17]Singh K,Agrawal NK,Gupta SK,et al.Increased expression of endosomal members of toll-like receptor family abrogates wound healing in patients with type 2 diabetes mellitus.Int Wound J,2016,13:927-935.
[18]Wifi MA,Assem M,Elsherif RH,et al.Toll-like receptors-2 and-9(TLR2andTLR9)gene polymorphism in patients with type 2diabetes and diabetic foot.Medicine,2017,96:e6760.
[2]Sridharan K,Sivaramakrishnan G.Growth factors for diabetic foot ulcers:mixed treatment comparison analysis of randomized clinical trials.Br J Clin Pharmacol,2018,84:434-444.
[3]Falck-Hansen M,Kassiteridi C,Monaco C.Toll-like receptors inatherosclerosis.Int J Mol Sci,2013,14:14008-14023.
[4]Christakos S,Dhawan P,Verstuyf A,et al.Vitamin D:metabolism,molecular mechanism of action,and pleiotropic effects.Physiol Rev,2016,96:365-408.
[5]Karásek D,VaverkováH.Diabetic dyslipidemia and microvascular complications of diabetes.Vnitrni lekarstvi,2018,64:17-24.
[6]Sheth JJ,Shah A,Sheth FJ,et al.Does vitamin D play a significant role in type 2 diabetes?.BMC Endocrine Disorders,2015,15:1-7.
[7]Lu Y,Zheng Y,Wang N,et al.The Relationship between vitamin D and type 2 diabetes is intriguing:glimpses from the spectchina study.Ann Nutr Metab,2017,71:195-202.
[8]He S,Yu S,Zhou Z,et al.Effect of vitamin D supplementation on fasting plasma glucose,insulin resistance and prevention of type 2 diabetes mellitus in non-diabetics:a systematic review and meta-analysis.Biomed Rep,2018,8:475-484.
[9]Stafeev IS,Michurina SS,Podkuychenko NV,et al.Interleukin-4restores insulin sensitivity in lipid-induced insulin-resistant adipocytes.Biochemistry,2018,83:498-506.
[10]Oliveira CD,Biddulph JP,Hirani V,et al.Vitamin D and inflammatory markers:cross-sectional analyses using data from the English longitudinal study of ageing(ELSA).J Nutr Sci,2017,6:e1.
[11]Elenius V,Palomares O,Waris M,et al.The relationship of serum vitamins A,D,E and LL-37 levels with allergic status,tonsillar virus detection and immune response.PLoS One,2017,12:e0172350.
[12]József L,Khreiss T,El K D,et al.Activation of TLR-9 induces IL-8 secretion through peroxynitrite signaling in human neutrophils.J Immunol,2006,176:1195-1202.
[13]Gu JQ,Wang DF,Yan G,et al.A Toll-like receptor 9-mediated pathway stimulates perilipin 3(TIP47)expression and induces lipid accumulation in macrophages.Am J Physiol Endocrinol Metab,2010,299:E593-E600.
[14]Ye L,Feng Z,Doycheva D,et al.CpG-ODN exerts a neuroprotective effect via the TLR9/pAMPK signaling pathway by activation of autophagy in a neonatal HIE rat model.Exp Neurol,2017,301:70-80.
[15]Singh K,Agrawal NK,Gupta SK,et al.Increased expression of TLR9 associated with pro-inflammatory S100A8 and IL-8 in diabetic wounds could lead to unresolved inflammation in type 2 diabetes mellitus(T2DM)cases with impaired wound healing.J Diabetes Complications,2016,30:99-108.
[16]Narumi K,Miyakawa R,Ueda R,et al.Proinflammatory proteins S100A8/S100A9 activate NK cells via interaction with RAGE.JImmunol,2015,194:5539-5548.
[17]Singh K,Agrawal NK,Gupta SK,et al.Increased expression of endosomal members of toll-like receptor family abrogates wound healing in patients with type 2 diabetes mellitus.Int Wound J,2016,13:927-935.
[18]Wifi MA,Assem M,Elsherif RH,et al.Toll-like receptors-2 and-9(TLR2andTLR9)gene polymorphism in patients with type 2diabetes and diabetic foot.Medicine,2017,96:e6760.