目的：探讨血清长链非编码RNA(lncRNA)无远端同源框6反义1(DLX6-AS1)、微小RNA-335-3p(miR-335-3p)与糖尿病视网膜病变(DR)患者微血管损伤的关系。

方法：前瞻性研究。选取2019-02/2021-12我院2型糖尿病(T2DM)患者160例，根据DR分期标准，分为无DR(NDR)组69例、非增殖型DR(NPDR)组48例、增殖型DR(PDR)组43例。比较三组患者血清lncRNA DLX6-AS1、miR-335-3p、血管内皮生长因子(VEGF)以及内皮细胞(ECs)、内皮祖细胞(EPCs)水平。Pearson法进行各指标相关性分析。Logistic回归模型分析影响T2DM患者发生DR的因素。

结果：NDR组、NPDR组、PDR组患者血清miR-335-3p表达水平及EPCs比例逐次减少，lncRNA DLX6-AS1、VEGF表达水平及ECs比例逐次增加(均P<0.05)。DR患者血清lncRNA DLX6-AS1与miR-335-3p负相关(r=-0.668，P<0.01)。NPDR组、PDR组血清lncRNA DLX6-AS1与miR-335-3p表达水平均呈负相关性(r=-0.647、-0.675，均P<0.01)，lncRNA DLX6-AS1与VEGF均呈正相关(r=0.619、0.630，均P<0.01)，VEGF与miR-335-3p均呈负相关(r=-0.625、-0.649，均P<0.01)； PDR组lncRNA DLX6-AS1与ECs呈正相关，与EPCs呈负相关(r=0.528、-0.594，均P<0.01)，miR-335-3p与ECs呈负相关，与EPCs均呈正相关(r=-0.554、0.586，均P<0.01)。多因素回归分析显示，lncRNA DLX6-AS1(OR=2.484，95%CI：1.366～4.516)、miR-335-3p(OR=2.171，95%CI：1.218～3.871、VEGF(OR=1.603，95%CI：1.115～2.304)是T2DM患者发生DR的危险因素(均P<0.05)。

结论：DR患者血清中lncRNA DLX6-AS1表达上调，miR-335-3p表达下调，lncRNA DLX6-AS1与miR-335-3p呈负相关，二者异常表达均与DR患者微血管损伤有关。

METHODS: A total of 160 patients with type 2 diabetes mellitus(T2DM)in our hospital from February 2019 to December 2021 were prospectively selected and divided into non-DR group(NDR, n=69), non-proliferative DR group(NPDR, n=48)and proliferative DR group(PDR, n=43)according to DR staging criteria. The serum levels of lncRNA DLX6-AS1, miR-335-3p, vascular endothelial growth factor(VEGF), endothelial cells(ECs), and endothelial progenitor cells(EPCs)were compared among the three groups. Pearson method was used for correlation analysis. Logistic regression model was used to analyze the influencing factors of DR in patients with T2DM.

RESULTS: The expression level of serum miR-335-3p and the proportion of EPCs in NDR, NPDR and PDR groups were gradually decreased, while the expression levels of DLX6-AS1 and VEGF and the proportion of ECs were gradually increased(all P<0.05). Serum lncRNA DLX6-AS1 was negatively correlated with miR-335-3p in patients with DR(r=-0.668, P<0.01). The expression levels of serum lncRNA DLX6-AS1 and miR-335-3p in NPDR and PDR groups were negatively correlated(r=-0.647, -0.675, all P<0.01), lncRNA DLX6-AS1 was positively correlated with VEGF(r=0.619, 0.630, all P<0.01), and VEGF was negatively correlated with miR-335-3p(r=-0.625, -0.649, all P<0.01). In the PDR group, lncRNA DLX6-AS1 was positively correlated with ECs, while it was negatively correlated with EPCs(r=0.528, -0.594, all P<0.01). The miR-335-3p was negatively correlated with ECs and it was positively correlated with EPCs(r=-0.554, 0.586, all P<0.01). Multivariate regression analysis showed that lncRNA DLX6-AS1(OR=2.484, 95%CI: 1.366-4.516), miR-335-3p(OR=2.171, 95%CI: 1.218-3.871)and VEGF(OR=1.603, 95%CI: 1.115-2.304)were risk factors for DR in T2DM patients(all P<0.05).

CONCLUSION:lncRNA DLX6-AS1 is up-regulated and miR-335-3p is down-regulated in serum of DR patients. lncRNA DLX6-AS1 is negatively correlated with miR-335-3p. Abnormal expressions of both are related to microvascular damage in DR patients.