目的:本研究检测了2型糖尿病(T2DM)患者血清细胞色素P450-可溶性环氧化物水解酶(CYP450-sEH)氧化脂素和抑郁症状与认知功能的关系。
方法:招募临床认知正常T2DM个体(NCT04455867)。使用贝克抑郁量表-II评估抑郁症状的严重程度(BDI-II;总分≤13表示轻度抑郁症状,≥14表示明显的抑郁症状)。评估了执行功能和言语记忆。采用超高效液相色谱串联质谱法对空腹血清氧化脂素进行定量。
结果:该研究包括85名具有轻微抑郁症状的参与者和27名具有明显症状的参与者(平均年龄:63.3±9.8岁,49%的女性)。在所有参与者中,较高浓度的亚油酸衍生的sEH(12,13-二羟基十八碳烯酸;DiHOME)和CYP450(12(13)-环氧十八碳烯酸;EpOME)代谢物与较差的执行功能相关(F1,101=6.094,p=0.015和F1,101=5.598,p=0.020)。多种sEH底物的浓度与抑郁症状相互作用以预测1)执行功能较差,包括9(10)-EpOME(F1,100=12.137,p<0.001),5(6)-环氧二十碳三烯酸(5(6)-EpETrE;F1,100=6.481,p=0.012)和11(12)-EpETrE(F1,100=4.409,p=0.038),2)言语记忆,包括9(10)-EpOME(F1,100=4.286,p=0.041),5(6)-EpETrE(F1,100=6.845,p=0.010),11(12)-EpETrE(F1,100=3.981,p=0.049)和14(15)-EpETrE(F1,100=5.019,p=0.027)。
结论:CYP450-sEH代谢产物和抑郁症状与认知的关联突出了CYP450-sEH通路在T2DM中的生物标志物和治疗潜力。
OBJECTIVE: This study examined serum cytochrome P450-soluble epoxide hydrolase (CYP450-sEH) oxylipins and depressive symptoms together in relation to cognitive performance in individuals with type 2 diabetes mellitus (T2DM).
METHODS: Clinically cognitively normal T2DM individuals were recruited (NCT04455867). Depressive symptom severity was assessed using the Beck Depression Inventory-II (BDI-II; total scores ≤13 indicated minimal depressive symptoms and ≥ 14 indicated significant depressive symptoms). Executive function and verbal memory were assessed. Fasting serum oxylipins were quantified by ultra-high-performance liquid chromatography tandem mass-spectrometry.
RESULTS: The study included 85 participants with minimal depressive symptoms and 27 with significant symptoms (mean age: 63.3 ± 9.8 years, 49 % women). In all participants, higher concentrations of linoleic acid derived sEH (12,13-dihydroxyoctadecamonoenoic acid; DiHOME) and CYP450 (12(13)-epoxyoctadecamonoenoic acid; EpOME) metabolites were associated with poorer executive function (F1,101 = 6.094, p = 0.015 and F1,101 = 5.598, p = 0.020, respectively). Concentrations of multiple sEH substrates interacted with depressive symptoms to predict 1) poorer executive function, including 9(10)-EpOME (F1,100 = 12.137, p < 0.001), 5(6)-epoxyeicosatrienoic acid (5(6)-EpETrE; F1,100 = 6.481, p = 0.012) and 11(12)-EpETrE (F1,100 = 4.409, p = 0.038), and 2) verbal memory, including 9(10)-EpOME (F1,100 = 4.286, p = 0.041), 5(6)-EpETrE (F1,100 = 6.845, p = 0.010), 11(12)-EpETrE (F1,100 = 3.981, p = 0.049) and 14(15)-EpETrE (F1,100 = 5.019, p = 0.027).
CONCLUSIONS: Associations of CYP450-sEH metabolites and depressive symptoms with cognition highlight the biomarker and therapeutic potential of the CYP450-sEH pathway in T2DM.