吲哚胺-2,3-双加氧酶/犬尿氨酸通路调控糖尿病并发抑郁症的机制研究

Study on the mechanism of indoleamine-2,3-dioxygenase/kynurenine pathway regulating diabetes mellitus complicated with depression

目的:研究吲哚胺-2,3-双加氧酶(IDO)/犬尿氨酸(KYN)通路(KP)调控糖尿病并发抑郁症的机制。方法:将30只SD大鼠随机分为对照组、模型组、干预组,每组10只。模型组和干预组复制糖尿病抑郁大鼠模型。于造模成功后第8天起,干预组灌胃给予IDO抑制剂1-甲基色氨酸(1-MT)溶液14 d。采用旷场实验评估大鼠行为学改变,酶联免疫吸附试验(ELISA)法检测海马组织去甲肾上腺素(NE)、5-羟色胺(5-HT)水平及血清炎性因子水平,高效液相色谱-荧光检测法测定大鼠血清KYN水平,Western blotting法检测海马组织IDO蛋白表达。结果:与对照组比较,模型组水平运动得分和垂直竖立行为得分下降,海马组织NE、5-HT水平及血清白细胞介素(IL)-4、IL-10水平降低,血清KYN、肿瘤坏死因子-α(TNF-α)、IL-6水平及IDO蛋白表达量升高(均P<0.05)。与模型组比较,干预组水平运动得分和垂直竖立行为得分升高,海马组织中NE、5-HT水平及血清IL-4、IL-10水平升高,血清KYN、TNF-α、IL-6水平及IDO蛋白表达水平降低(均P<0.05)。结论:IDO/KP通路可能通过降低NE和5-HT水平、加重炎性反应来促进糖尿病并发抑郁症的发生发展。

Objective:To study the mechanism of indoleamine-2,3-dioxygenase(IDO)/kynurenine(KYN)pathway(KP)regulating diabetes mellitus complicated with depression.Methods:A total of 30 SD rats were randomly divided into control group,model group and intervention group,with 10 cases in each group.The diabetic depression rat model was established in the model group and the intervention group.From the 8th day after the establishment of the model,the intervention group was given IDO inhibitor 1-methyltryptophan(1-MT)solution by intragastric administration for 14 days.The behavioral changes of rats were evaluated by open field test.The levels of norepinephrine(NE),5-hydroxytryptamine(5-HT)and serum inflammatory factors in hippocampus were detected by enzyme-linked immunosorbent assay(ELISA).The level of serum KYN was determined by high performance liquid chromatography-fluorescence detection,and the expression of IDO protein in hippocampus was detected by Western blotting.Results:Compared with the control group,the scores of horizontal movement and vertical erection behavior in the model group decreased,the levels of NE and 5-HT in hippocampus and the levels of interleukin(IL)-4 and IL-10 in serum decreased,while the levels of serum KYN,tumor necrosis factor-α(TNF-α),IL-6 and IDO protein expression increased in the model group(all P<0.05).Compared with the model group,the scores of horizontal movement and vertical erection behavior in the intervention group increased,the levels of NE and 5-HT in hippocampus and the levels of IL-4 and IL-10 in serum increased,while the levels of serum KYN,TNF-α,IL-6 and IDO protein expression decreased in the intervention group(all P<0.05).Conclusion:IDO/KP pathway may promote the occurrence and development of diabetes mellitus complicated with depression by reducing the levels of NE and 5-HT and aggravating the inflammatory response.