胰岛素受体底物-1、内皮型一氧化氮合酶与胰岛素抵抗、糖尿病下肢血管病变及糖尿病足发病关系的临床研究

The relationship of IRS-1 and endothelial nitric oxide synthase(eNOS) with insulin resistance and the development of diabetic lower extremity arterial lesions and diabetic foot

目的探讨胰岛素受体底物-1(IRS-1)和内皮型一氧化氮合酶(eNOS)与糖尿病下肢血管病变及糖尿病足(DF)的发病关系,为临床预防及治疗糖尿病下肢血管病变提供试验依据。方法采用RT-PCR检测糖尿病足溃疡(DFU)组、糖尿病合并下肢血管病变(T2DM+PAD)组、T2DM组及正常对照(NC)组外周血单个核细胞IRS-1及eNOS mRNA表达,并采集各组临床生化资料,稳态模型评估胰岛素抵抗指数(HOMA-IR)。采用方差分析,秩和检验及直线相关进行组间比较及各指标相关关系的分析。结果 T2DM、T2DM+PAD和DFU组TG、TC、FPG、2hPG、HbA1c、HOMA-IR均高于NC组(P<0.05),T2DM+PAD和DFU组TG,LDL-C及病程高于T2DM组,HDL-C低于T2DM组(P<0.05)。NC组IRS-1mRNA 2-ΔΔCT和eNOS mRNA 2-ΔΔCT表达最高[1.00(0.70,1.41),1.00(0.65,1.53)],DFU组最低[0.26(0.10,0.62),0.18(0.11,0.31)](P<0.05)。T2DM、T2DM+PAD、DFU组IRS-1与eNOS mRNA表达呈直线相关(r=0.4638、0.5471、0.5023,P<0.05)。结论 IRS-1可能通过下调eNOS的表达参与了糖尿病下肢血管病变及DF的发生发展。

Objective To study the relationship of IRS-1 and endothelial nitric oxide synthase （eNOS） with the development of diabetic lower extremity arterial lesions and diabetic foot. Methods The expressions of IRS-1 and eNOS in peripheral blood mononuclear cells were tested by Real-Time PCR in patients with diabetic foot ulcers（DFU）, T2DM peripheral arterial disease（T2DM＋PAD）, T2DM and normal control（NC） groups. Clinical and biochemical data of each group were collected and their HOMA- IR was calculated. Analysis of variance （ANOVA） ,kruskal-wallis test and linear correlation analysis were applied for the intergroup analysis and correlation analysis. Results TG, TC, FPG, 2 hPG, HbA1 c and HOMA-IR were lower in NC group than in T2DM, T2DM＋PAD and DFU groups（P〈0.05）. TG, LDL-C and clinical course were higher in T2DM＋PAD and DFU groups than in T2DM group, while HDL-C was lower（P〈0. 05）. The expressions of IRS-1 and eNOS mRNA were highest in NC group [1.00（0. 70, 1.41）, 1.00 （ 0.65, 1.53 ） ], while the DFU group has the lowest data [- 0.26 （0. 10, 0.62 ）, 0.18 （0.11, 0. 31）]（P〈0.05）. The expression of IRS-1 had linear correlation to that of eNOS in T2DM, T2DM＋PAD,and DFU groups（r=0. 4638,0. 5471,0. 5023,P〈0.05）. Conclusion IRS-1 may participate in the development of diabetic lower extremity arteriallesions and diabetic foot by suppressing eNOS expression.