糖耐量受损患者血清eNOS mRNA和TRB3mRNA表达与疾病干预的相关性研究
|
摘要
目的探讨血清内皮型一氧化氮合酶(eNOS)mRNA和同源蛋白3(tribbleshomologprotein3,TRB3)mRNA表达在生活方式干预治疗糖耐量受损(IGT)疾病中的应用价值。方法收集58例接受生活方式干预治疗的糖耐量受损患者(治疗前组和治疗后组)和53例健康人群(对照组)的血液及临床资料,采用实时荧光定量PCR(real-time-PCR,RT-PCR)技术检测各组研究对象的血清eNOS mRNA和TRB3mRNA表达。所有研究对象均接受葡萄糖耐量试验和胰岛素释放试验,通过空腹血糖(FPG)及空腹胰岛素(FINS)水平计算得到胰岛素抵抗指数(HOMA-IR)。采用高效液相色谱仪检测糖化血红蛋白(HbA1c)水平。比较分析以上指标的变化与IGT的关系。采用受试者工作特征曲线(ROC曲线)评价血清eNOSmRNA和TRB3mRNA在IGT中的临床意义。结果在对照组、治疗后组和治疗前组中,血清eNOSmRNA和TRB3mRNA的表达量分别为0.93±0.23,0.69±0.20,0.19±0.10和0.35±0.14,0.62±0.21,0.96±0.25。TRB3mRNA在治疗前组的表达显著高于治疗后组,在治疗后组的表达显著高于对照组(F=93.27,P<0.01);而eNOSmRNA在治疗前组的表达显著低于与治疗后组,在治疗后组的表达显著低于对照组(F=89.65,P<0.01),差异均有统计学意义。在对照组、治疗后组和治疗前组中,FPG(mmol/L),FINs(μU/ml),HbA1c(%)水平及HOMA-IR分别为5.07±0.41,7.23±7.57,5.29±0.36,2.13±0.47;5.51±0.47,5.73±0.35,2.87±0.77和6.12±0.59,11.39±11.71,6.17±0.39,3.17±0.83。治疗前组的FPG,FINs,HbA1c水平及HOMA-IR分别与治疗后组比较显著增高,治疗后组的各项指标与对照组比较显著增高,差异均有统计学意义(F=60.03～110.51,均P<0.01)。血清eNOSmRNA和TRB3mRNA在治疗前组和治疗后组中的表达具有负相关性(r=-0.867,-0.826,均P<0.01)。血清eNOSmRNA在治疗前组和治疗后组中的表达与FPG,FINs,HbA1c水平及HOMA-IR呈负相关性(r=-0.779,-0.739,-0.727,-0.755,均P<0.01),(r=-0.726,-0.689,-0.667,-0.696,均P<0.01),而TRB3mRNA在治疗前组和治疗后组中的表达与FPG,FINs,HbA1c水平及HOMA-IR呈正相关性(r=0.823,0.769,0.753,0.797,均P<0.01),(r=0.753,0.697,0.685,0.726,均P<0.01)。ROC曲线分析显示,eNOSmRNA和TRB3mRNA的AUC分别为[0.858(95%CI:0.756～0.960,P<0.01),0.862(95%CI:0.753～0.970,P<0.01)]。结论血清eNOSmRNA和TRB3mRNA的检测可应用于评价生活方式干预治疗IGT疾病的效果,并可能为IGT及2型糖尿病的治疗提供有效的基因学依据。
Objective To explore the clinical value of serum expression of eNOSmRNA and TRB3 mRNA in lifestyle intervention treatment for impaired glucose tolerance.Methods These serumal and clinical data from 58 patients with impaired glucose tolerance,who acquired lifestyle intervention treatment(pre-treatment group and post-treatment group),and 53 normal people(control group)were collected.Detecting expression of eNOSmRNA and TRB3 mRNA in serum was used the method of the real time fluorescence quantitative PCR(real-time-PCR,RT-PCR).All the investigated subjects underwent glucose tolerance tests and insulin release tests.Insulin resistance index(HOMA-IR)was calculated by fasting blood glucose(FPG)and fasting insulin(FINS)levels.The level of glycosylated hemoglobin(HbA1 c)was detected by high performance liquid chromatograph.The relationships between the changes of the above indexes and IGT were comparatively analyzed.Clinical significances of serum eNOSmRNA and TRB3 mRNA in IGT were assessed by ROC curve.Results The expression of serum eNOSmRNA and TRB3 mRNA in the control,posttreatment and pretreatment groups were 0.93±0.23,0.69±0.20,0.19±0.10 and 0.35±0.14,0.62±0.21,0.96±0.25,respectiyely.The expression of TRB3 mRNA was significantly higher and which of eNOSmRNA was significantly lower in the pretreatment group than those in the post treatment group.Similar situations also occurred in the post treatment group than those in the control group for the two markers,their differences were statistically significant(F=93.27,89.65,all P<0.01).The levels of FPG(mmol/L),FINs(μU/ml),HbA1 c(%)and HOMA-IR in the control group,the treatment group and the pre-treatment group were(5.07±0.41,7.23±7.57,5.29±0.36,2.13±0.47),(5.51±0.47,8.53±7.49,5.73±0.35,2.87±0.77),(6.12±0.59,11.39±11.71,6.17±0.39,3.17±0.83),respectively,which of them in the pre-treatment group were significantly higher than those in the post-treatment group,as were similar in the post-treatment group compared with those in the control group.The above differences were statically significant(F=60.03～110.51,all P<0.001).It was observed that expression of eNOSmRNA and TRB3 mRNA in the pretreatment and posttreatment groups was inversely correlated(r=-0.867,-0.826,all P <0.01)and eNOSmRNA in the pretreatment and posttreatment groups,respectively,help these significant negative correlations with FPG,FINs,HbA1 cand HOMA-IR[r=-0.779,-0.739,-0.727,-0.755,P<0.01),(r=-0.726,-0.689,-0.667,-0.696,all P<0.01)respectively,while TRB3 mRNA had these positive correlations[(r=0.823,0.769,0.753,0.797,all P<0.01),(r=0.753,0.697,0.685,0.726,all P<0.01)].The ROC curve analysis showed that the AUC of eNOSmRNA and TRB3 mRNA were[0.858(95%CI:0.756 to 0.960,P<0.01)and 0.862(95%CI:0.753 to 0.970,P<0.01)].Conclusion Detection of serum eNOSmRNA and TRB3 mRNA can be used evaluating the effect of lifestyle intervention for IGT and may provide an effective genetic basis for treatment of IGT and type 2 diabetes.
Objective To explore the clinical value of serum expression of eNOSmRNA and TRB3 mRNA in lifestyle intervention treatment for impaired glucose tolerance.Methods These serumal and clinical data from 58 patients with impaired glucose tolerance,who acquired lifestyle intervention treatment(pre-treatment group and post-treatment group),and 53 normal people(control group)were collected.Detecting expression of eNOSmRNA and TRB3 mRNA in serum was used the method of the real time fluorescence quantitative PCR(real-time-PCR,RT-PCR).All the investigated subjects underwent glucose tolerance tests and insulin release tests.Insulin resistance index(HOMA-IR)was calculated by fasting blood glucose(FPG)and fasting insulin(FINS)levels.The level of glycosylated hemoglobin(HbA1 c)was detected by high performance liquid chromatograph.The relationships between the changes of the above indexes and IGT were comparatively analyzed.Clinical significances of serum eNOSmRNA and TRB3 mRNA in IGT were assessed by ROC curve.Results The expression of serum eNOSmRNA and TRB3 mRNA in the control,posttreatment and pretreatment groups were 0.93±0.23,0.69±0.20,0.19±0.10 and 0.35±0.14,0.62±0.21,0.96±0.25,respectiyely.The expression of TRB3 mRNA was significantly higher and which of eNOSmRNA was significantly lower in the pretreatment group than those in the post treatment group.Similar situations also occurred in the post treatment group than those in the control group for the two markers,their differences were statistically significant(F=93.27,89.65,all P<0.01).The levels of FPG(mmol/L),FINs(μU/ml),HbA1 c(%)and HOMA-IR in the control group,the treatment group and the pre-treatment group were(5.07±0.41,7.23±7.57,5.29±0.36,2.13±0.47),(5.51±0.47,8.53±7.49,5.73±0.35,2.87±0.77),(6.12±0.59,11.39±11.71,6.17±0.39,3.17±0.83),respectively,which of them in the pre-treatment group were significantly higher than those in the post-treatment group,as were similar in the post-treatment group compared with those in the control group.The above differences were statically significant(F=60.03～110.51,all P<0.001).It was observed that expression of eNOSmRNA and TRB3 mRNA in the pretreatment and posttreatment groups was inversely correlated(r=-0.867,-0.826,all P <0.01)and eNOSmRNA in the pretreatment and posttreatment groups,respectively,help these significant negative correlations with FPG,FINs,HbA1 cand HOMA-IR[r=-0.779,-0.739,-0.727,-0.755,P<0.01),(r=-0.726,-0.689,-0.667,-0.696,all P<0.01)respectively,while TRB3 mRNA had these positive correlations[(r=0.823,0.769,0.753,0.797,all P<0.01),(r=0.753,0.697,0.685,0.726,all P<0.01)].The ROC curve analysis showed that the AUC of eNOSmRNA and TRB3 mRNA were[0.858(95%CI:0.756 to 0.960,P<0.01)and 0.862(95%CI:0.753 to 0.970,P<0.01)].Conclusion Detection of serum eNOSmRNA and TRB3 mRNA can be used evaluating the effect of lifestyle intervention for IGT and may provide an effective genetic basis for treatment of IGT and type 2 diabetes.
引文
[1]龚清海,应焱燕,李辉,等.生活方式干预对成年糖耐量受损患者血糖影响的系统评价及meta分析[J].中华内分泌代谢杂志,2014,30(7):576-581.GONG Qinghai,YIN Yanyan,LI Hui,et al.Relationship between lifestyle interventions and glycemic level in adults with impaired glucose tolerance:asystematic review and meta-analysis[J].Chinese Journal of Endocrinology and Metabolism,2014,30(7):576-581.
[2]李金梁,杨兆颖,陈海军,等.瑞舒伐他汀改善胰岛素抵抗的内皮细胞功能的研究[J].中国医刊,2015,50(10):56-59.LI Jingliang,YANG Zhaoying,CHEN Haijun,et al.Studies on the improvement of endothelial cell function in insulin resistance[J].Chinese Journal of Medicine,2015,50(10):56-59.
[3]董少婷.TRIB3基因的研究进展[J].中国基层医药,2016,23(4):625-627.DONG Shaoting.Progress of TIRB3gene research[J].Chinese Journal of Primary Medicine and Pharmacy,2016,23(4):625-627.
[4]孙涛,张熊,张涛.血清chemerinmRNA和TRB3mR-NA检测在2型糖尿病患者胰岛素抵抗预测中的应用价值[J].临床和实验医学杂志,2017,16(19):1922-1925.SUN Tao,ZHANG Xiong,ZHANG Tao.The application of detecting the levels of serum chemerinmR-NA and TRB3mRNA in type 2diabetes with insulin resistance[J].Journal of Clinical and Experimental Medicine,2017,16(19):1922-1925.
[5]TABAK A G,JOKELA M,AKBARALY T N,et al.Trajectories of glycaemia,insulin sensitivity,and insulin secretion before diagnosis of type 2diabetes:an analysis from the Whitehall II study[J].Lancet(London England),2009,373(9682):2215-2221.
[6]LUTZ A H,BLUMENTHAL J B,LANDERS RAM-OS R Q,et al.Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2diabetes[J].J Appl Physiol,2016,121(1):36-41.
[7]WALDMAN B,JENKINS AJ,DAVIS TM,et al.HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes[J].Diabetes Care,2014,37(8):2351-2358.
[8]李晓媚,付四海,雷艳萍,等.一氧化氮合酶抑制物在糖尿病大鼠骨骼肌收缩功能损害中的作用[J].中国医师杂志,2017,19(10);1462-1468.LI Xiaomei,FU Sihai,LEI Yanping,et al.Role of nitric oxide synthase inhibitor in the skeletal muscle contractile dysfunction of type 2 diabetic rats[J].Journal of Chinese Physician,2017,19(10);1462-1468.
[9]FENG Xiaomeng,XIA Gao,ZHI Yao,et al.Low apoA-I is associated with insulin resistance in patients with impaired glucose tolerance:a cross-sectional study[J].Lipids Health Disease,2017,16(1):69.
[10]HASEGAWA Y,SAITO T,OGIHARA T,et al.Blockade of the nuclear factor-κB pathway in the endothelium prevents insulin resistance and prolongs life spans[J].Circulation,2012,125(9):1122-1133.
[11]HUANG P L.eNOS,metabolic syndrome and cardiovascular disease[J].Trends Endocrinol Metab,2009,20(6):295-302.
[12]张鹏程,兰崴,刘竹青,等.有氧运动联合抗阻力运动对糖尿病大鼠血管内皮功能的作用及其对磷脂酰肌醇-3激酶/蛋白激酶B/内皮型一氧化氮合酶通路的影响[J].中国糖尿病杂志,2017,25(3):264-271.ZHANG Pengcheng,LAN Wei,LIU Zhuqing,et al.Effects of aerobic exercise combined with resistive exercise on vascular endothelial function and its impact on Phosphatidylinositol-3 Kinase/Protein Kinase B/Endothelial nitric oxide synthase pathway for diabetic rats[J].Chinese Journal of Diabetes,2017,25(3):264-271.
[13]ONYANGO A N.The contribution of singlet oxygen to insulin resistance[J].Oxid Med Cell Longev,2017,7:8765972.
[14]曹梅,赵一卉,韩睿,等.EGCG调控骨骼肌组织TRB3表达改善胰岛素抵抗[J].西南师范大学学报(自然科学版),2017,42(11):37-43.CAO Mei,ZHAO Yihui,HAN Rui,et al.EGCG improves insulin resistance by regulating the expression of TRB3in muscle tissue[J].Journal of Southwest China Normal University(Natural Science E-dition),2017,42(11)37-43.
[15]董静,刘尊,赵林杰.TRB3在运动改善胰岛素抵抗中的作用[J].医学综述,2012,18(14):2172-2174.DONG Jing,LIU Zun,ZHAO Linjie.The role of TRB3in exercise improving insulin resistance[J].Medical Recapitulate,2012,18(14):2172-2174.
[16]李琳,徐瑜.生活方式干预对2型糖尿病患者血糖控制的影响[J].上海交通大学学报(医学版),2017,37(6):871-875.LI Lin,XU Yu.Effects of lifestyle intervention on glucose control in people with type 2diabetes[J].Journal of Shanghai Jiaotong University(Medical Science),2017,37(6):871-875.
[17]李全双,邓演超,吴燕,等.初诊2型糖尿病患者综合干预后血栓前状态分子标志物的变化[J].现代检验医学杂志,2015,30(2):36-38.LI Quanshuang,DENG Yanchao,WU Yan,et al.Changes in molecular markers of prethrombotic state for newly diagnosed Type 2diabetic patients after comprehensive intervention[J].Journal of Modern Laboratory Medicine,2015,30(2):36-38.
[2]李金梁,杨兆颖,陈海军,等.瑞舒伐他汀改善胰岛素抵抗的内皮细胞功能的研究[J].中国医刊,2015,50(10):56-59.LI Jingliang,YANG Zhaoying,CHEN Haijun,et al.Studies on the improvement of endothelial cell function in insulin resistance[J].Chinese Journal of Medicine,2015,50(10):56-59.
[3]董少婷.TRIB3基因的研究进展[J].中国基层医药,2016,23(4):625-627.DONG Shaoting.Progress of TIRB3gene research[J].Chinese Journal of Primary Medicine and Pharmacy,2016,23(4):625-627.
[4]孙涛,张熊,张涛.血清chemerinmRNA和TRB3mR-NA检测在2型糖尿病患者胰岛素抵抗预测中的应用价值[J].临床和实验医学杂志,2017,16(19):1922-1925.SUN Tao,ZHANG Xiong,ZHANG Tao.The application of detecting the levels of serum chemerinmR-NA and TRB3mRNA in type 2diabetes with insulin resistance[J].Journal of Clinical and Experimental Medicine,2017,16(19):1922-1925.
[5]TABAK A G,JOKELA M,AKBARALY T N,et al.Trajectories of glycaemia,insulin sensitivity,and insulin secretion before diagnosis of type 2diabetes:an analysis from the Whitehall II study[J].Lancet(London England),2009,373(9682):2215-2221.
[6]LUTZ A H,BLUMENTHAL J B,LANDERS RAM-OS R Q,et al.Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2diabetes[J].J Appl Physiol,2016,121(1):36-41.
[7]WALDMAN B,JENKINS AJ,DAVIS TM,et al.HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes[J].Diabetes Care,2014,37(8):2351-2358.
[8]李晓媚,付四海,雷艳萍,等.一氧化氮合酶抑制物在糖尿病大鼠骨骼肌收缩功能损害中的作用[J].中国医师杂志,2017,19(10);1462-1468.LI Xiaomei,FU Sihai,LEI Yanping,et al.Role of nitric oxide synthase inhibitor in the skeletal muscle contractile dysfunction of type 2 diabetic rats[J].Journal of Chinese Physician,2017,19(10);1462-1468.
[9]FENG Xiaomeng,XIA Gao,ZHI Yao,et al.Low apoA-I is associated with insulin resistance in patients with impaired glucose tolerance:a cross-sectional study[J].Lipids Health Disease,2017,16(1):69.
[10]HASEGAWA Y,SAITO T,OGIHARA T,et al.Blockade of the nuclear factor-κB pathway in the endothelium prevents insulin resistance and prolongs life spans[J].Circulation,2012,125(9):1122-1133.
[11]HUANG P L.eNOS,metabolic syndrome and cardiovascular disease[J].Trends Endocrinol Metab,2009,20(6):295-302.
[12]张鹏程,兰崴,刘竹青,等.有氧运动联合抗阻力运动对糖尿病大鼠血管内皮功能的作用及其对磷脂酰肌醇-3激酶/蛋白激酶B/内皮型一氧化氮合酶通路的影响[J].中国糖尿病杂志,2017,25(3):264-271.ZHANG Pengcheng,LAN Wei,LIU Zhuqing,et al.Effects of aerobic exercise combined with resistive exercise on vascular endothelial function and its impact on Phosphatidylinositol-3 Kinase/Protein Kinase B/Endothelial nitric oxide synthase pathway for diabetic rats[J].Chinese Journal of Diabetes,2017,25(3):264-271.
[13]ONYANGO A N.The contribution of singlet oxygen to insulin resistance[J].Oxid Med Cell Longev,2017,7:8765972.
[14]曹梅,赵一卉,韩睿,等.EGCG调控骨骼肌组织TRB3表达改善胰岛素抵抗[J].西南师范大学学报(自然科学版),2017,42(11):37-43.CAO Mei,ZHAO Yihui,HAN Rui,et al.EGCG improves insulin resistance by regulating the expression of TRB3in muscle tissue[J].Journal of Southwest China Normal University(Natural Science E-dition),2017,42(11)37-43.
[15]董静,刘尊,赵林杰.TRB3在运动改善胰岛素抵抗中的作用[J].医学综述,2012,18(14):2172-2174.DONG Jing,LIU Zun,ZHAO Linjie.The role of TRB3in exercise improving insulin resistance[J].Medical Recapitulate,2012,18(14):2172-2174.
[16]李琳,徐瑜.生活方式干预对2型糖尿病患者血糖控制的影响[J].上海交通大学学报(医学版),2017,37(6):871-875.LI Lin,XU Yu.Effects of lifestyle intervention on glucose control in people with type 2diabetes[J].Journal of Shanghai Jiaotong University(Medical Science),2017,37(6):871-875.
[17]李全双,邓演超,吴燕,等.初诊2型糖尿病患者综合干预后血栓前状态分子标志物的变化[J].现代检验医学杂志,2015,30(2):36-38.LI Quanshuang,DENG Yanchao,WU Yan,et al.Changes in molecular markers of prethrombotic state for newly diagnosed Type 2diabetic patients after comprehensive intervention[J].Journal of Modern Laboratory Medicine,2015,30(2):36-38.