抑郁症患者胶质细胞源性神经营养因子、Nod样受体蛋白3炎症小体表达水平及其诊断价值

田海华 刘纪猛 徐国安

[摘要] 目的 探究抑郁癥患者胶质细胞源性神经营养因子（GDNF）、Nod样受体蛋白3（NLRP3）炎症小体表达水平变化及其诊断价值。 方法 选择2018年1月～2019年6月浙江省宁波市康宁医院（以下简称“我院”）情感障碍科收治的100例抑郁症患者作为抑郁症组，另选择同期在我院进行常规体检的60名健康人群作为对照组。比较两组患者以及不同严重程度的抑郁症患者GDNF表达情况及血清NLRP3炎症小体水平，分析抑郁严重程度与GDNF、血清NLRP3炎症小体水平的相关性，计算GDNF、NLRP3炎症小体单项检测以及联合检测在诊断抑郁症中的诊断效能。 结果 抑郁症组GDNF水平明显低于对于对照组，血清NLRP3炎症小体水平明显高于对照组，差异均有统计学意义（均P < 0.05）。不同严重程度抑郁症患者的GDNF及NLRP3炎症小体水平比较，差异有统计学意义（P < 0.05）。与轻度抑郁组比较，中度抑郁组、重度抑郁组GDNF水平降低、NLRP3炎症小体水平升高，差异均有统计学意义（均P < 0.05），与中度抑郁组比较，重度抑郁组GDNF水平降低、NLRP3炎症小体水平升高，差异均有统计学意义（均P < 0.05）。GDNF表达水平与抑郁症严重程度均呈负相关（r = -0.603，P < 0.05），血清NLRP3炎症小体表达水平与抑郁症严重程度均呈正相关（r = 0.762，P < 0.05）。GDNF、NLRP3炎症小体联合检测诊断抑郁症的敏感度和特异度明显高于GDNF、NLRP3炎症小体单项检测，且有较好的特异度。结论 GDNF及血清NLRP3炎症小体的异常表达与抑郁症的发生、发展密切相关，GDNF、NLRP3炎症小体联合检测有助于抑郁症诊断和病情评估。

[关键词] 抑郁症;胶质细胞源性神经营养因子;Nod样受体蛋白3炎症小体;诊断价值

[中图分类号] R651.2          [文献标识码] A          [文章编号] 1673-7210（2020）03（b）-0148-04

[Abstract] Objective To investigate the changes of glial cell-derived neurotrophic factor （GDNF） and nod-like receptor protein 3 （NLRP3） inflammasome in major depressive disorder patients and analyze the diagnostic value. Methods A total of 100 patients with major depressive disorder admitted to the Department of Affective Disorder， Ningbo Kangning Hospital （“our hospital” for short） from January 2018 to June 2019 were selected as the depression group. A total of 60 healthy people underwent routine physical examination in our hospital during the same period were selected as the control group. The expression of serum GDNF and NLRP3 inflammasome were compared between the two groups of patients and patients with depression of different severity. The correlation between the severity of depression and the diagnostic efficacy of GDNF and NLRP3 inflammasome single test and combined test in diagnosing depression were calculated. Results The level of GDNF in the depression group was significantly lower than that of the control group， and the serum NLRP3 level of the inflamatome was significantly higher than that of the control group， with statistically significant differences （all P < 0.05）. The levels of GDNF and NLRP3 in patients with depression of different severity were statistically significant differences （P < 0.05）. Compared with the mild depression group， the GDNF level in the moderate depression group and the severe depression group were decreased and the NLRP3 inflammasome was increased， the differences were statistically significant （all P < 0.05）. Compared with the moderate depression group， the GDNF level in the severe depression group were decreased and the NLRP3 inflammasome was increased， the differences were statistically significant （all P < 0.05）. The expression level of GDNF was negatively correlated with the severity of depression （r = -0.603， P < 0.05）， while the expression level of serum NLRP3 inflamosome was positively correlated with the severity of depression （r = 0.762， P < 0.05）. The sensitivity and specificity of combined detection of GDNF and NLRP3 inflammasome in diagnosing depression were significantly higher than that of single detection of GDNF and NLRP3 inflammasome and the combined detection has good specificity. Conclusion The abnormal expression of GDNF and serum NLRP3 inflammarosome is closely related to the occurrence and development of depression， and the combined detection of GDNF and NLRP3 inflammarosome is helpful for the diagnosis and condition evaluation of depression.

NLRP3炎癥小体功能失调可导致免疫系统炎症的激活从而参与抑郁症的发生发展[23-24]。本研究结果显示，抑郁症患者血清NLRP3炎症小体水平明显高于健康人群，且NLRP3炎症小体的水平随着抑郁程度的增加而升高。提示NLRP3炎症小体与抑郁症的发生发展有关。血清NLRP3炎症小体随着抑郁程度的加重而增加，可将其作为评估抑郁症严重程度的客观指标。

单项检测NRLP3炎症小体，GDNF对诊断抑郁症有一定效能，但灵敏度不高，特异度不强，临床应用价值受限。两指标的联合检测诊断抑郁症时AUC、灵敏度及特异度均高于单项检测。提示联合检测NRLP3炎症小体，GDNF有利于提高抑郁症的诊断能力。Pearson相关分析发现，GDNF表达与抑郁症严重程度呈负相关。NLRP3炎症小体水平与抑郁症严重程度呈正相关。GDNF及NLRP3炎症小体水平可作为诊断、评估抑郁症症状程度的可靠指标。

综上所述，抑郁症发生时患者GDNF表达下降，NLRP3炎症小体表达异常升高。GDNF、NLRP3炎症小体可能参与了抑郁症的发生发展。GDNF、NLRP3炎症小体联合检测可作为参考指标用于抑郁症的诊断和病情评估。

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（收稿日期：2019-09-24  本文编辑：刘永巧）