血清Sirt1、Sestrin2与2型糖尿病并发糖尿病周围神经病变患者的关系研究

Relationship between serum Sirt1,Sestrin 2 and type 2 diabetes patients complicated with diabetes peripheral neuropathy

目的 探究血清沉默信息调节因子1(Sirt1)、Sestrin2与2型糖尿病(T2DM)并发周围神经病变(DPN)的关系。方法 选取2020年3月至2022年3月新疆医科大学第一附属医院收治的T2DM患者142例,根据DPN发生情况分为非DPN组(85例)和DPN组(57例),另选取同期体检健康者为健康对照组(50例),对比健康对照组、非DPN组、DPN组血清Sirt1、Sestrin2水平,对比非DPN组与DPN组氧化应激指标[丙二醛(MDA)、总抗氧化能力(T-AOC)、超氧化物歧化酶(SOD)]及外周血单核细胞Toll样受体4(TLR-4)、核转录因子(NF)-κB信使核糖核酸(mRNA)表达水平,分析血清Sirt1、Sestrin2与DPN患者氧化应激指标、外周血单核细胞TLR-4和NF-κB mRNA表达水平的相关性,采用单因素和多因素分析T2DM发生DPN的影响因素。结果 与健康对照组比较,非DPN组和DPN组血清Sirt1水平降低(P<0.05),血清Sestrin2水平升高(P<0.05);与非DPN组比较,DPN组血清Sirt1、Sestrin2水平降低(P<0.05)。与非DPN组比较,DPN组血清MDA及外周血单核细胞TLR-4、NF-κB mRNA表达水平升高(P<0.05),血清SOD水平降低(P<0.05),血清T-AOC水平差异无统计学意义(P>0.05)。Pearson检验结果显示,DPN患者血清Sirt1、Sestrin2与SOD呈正相关(P<0.05),与MDA、TLR-4、NF-κB呈负相关(P<0.05)。多因素分析显示,年龄增大(≥63岁)、T2DM病程偏长(≥8年)、糖化血红蛋白(HbA1c)水平升高(≥9%)、糖尿病视网膜病变(DR)、高密度脂蛋白(HDL)水平降低(<1 mmol/L)、Sirt1降低(<8 ng/mL)、Sestrin2降低(<14 ng/mL)是DPN的危险因素(P<0.05)。结论 DPN患者血清Sirt1、Sestrin2水平下降,可能与氧化应激、炎症反应过度激活有关,有望成为预测DPN风险的分子标志物。

Objective To explore the relationship between serum silent information regulator 1(Sirt1),Sestrin 2 and type 2 diabetes mellitus(T2DM)patients complicated with diabetes peripheral neuropathy(DPN).Methods A total of 142 patients with T2DM who were admitted to the First Affiliated Hospital of Xinjiang Medical University from March 2020 to March 2022 were selected.According to the occurrence of DPN,they were divided into non-DPN group(85 cases)and DPN group(57 cases).In addition,healthy people in physical examination during the same period were selected as healthy control group(50 cases),the serum Sirt1 and Sestrin2 levels in the healthy control group,non-DPN group and DPN group were compared,the oxidative stress indicators[malondialdehyde(MDA),total antioxidant capacity(T-AOC),superoxide dismutase(SOD)],peripheral blood mononuclear cells Toll-like receptor 4(TLR-4)and nuclear transcription factor(NF)-κB messenger ribonucleic acid(mRNA)expression levels between non-DPN group and DPN group were compared,the correlation between serum Sirt1 and Sestrin2 and oxidative stress indicators,peripheral blood mononuclear cells TLR-4 and NF-κB mRNA expression levels in patients with DPN was analyzed.Univariate and multivariate analysis were used to analyze the influencing factors of DPN in T2DM.Results Compared with the healthy control group,the serum Sirt1 level in the non-DPN group and DPN group was lower significantly(P<0.05),and the serum Sestrin2 level was higher significantly(P<0.05).Compared with the non-DPN group,the serum Sirt1 and Sestrin2 levels in the DPN group were significantly lower(P<0.05).Compared with non-DPN group,serum MDA and peripheral blood mononuclear cells TLR-4 and NF-κB mRNA expression levels in the DPN group was significantly higher(P<0.05),serum SOD was significantly lower(P<0.05),and the difference in serum T-AOC in two groups was not statistically significant(P>0.05).Pearson test results showed that serum Sirt1,Sestrin2 were positively correlated with SOD in patients with DPN(P<0.05),and they were negatively correlated with MDA,TLR-4,NF-κB(P<0.05).Multivariate analysis showed that increased age(≥63 years),longer duration of T2DM(≥8 years),increased glycated hemoglobin(HbA1c)(≥9%),decreased diabetes retinopathy(DR),high-density lipoprotein(HDL)(<1 mmol/L),decreased Sirt1(<8 ng/mL),and decreased Sestrin2(<14 ng/mL)were the risk factors for DPN(P<0.05).Conclusion The serum Sirt1 and Sestrin2 levels in patients with DPN decreased significantly,which may be related to oxidative stress and over activation of inflammatory reaction,and which may become molecular markers to predict the risk of DPN.