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.
引文
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