抑郁癥患者膠質(zhì)細(xì)胞源性神經(jīng)營養(yǎng)因子、Nod樣受體蛋白3炎癥小體表達(dá)水平及其診斷價(jià)值

田海華 劉紀(jì)猛 徐國安

[摘要] 目的 探究抑郁癥患者膠質(zhì)細(xì)胞源性神經(jīng)營養(yǎng)因子（GDNF）、Nod樣受體蛋白3（NLRP3）炎癥小體表達(dá)水平變化及其診斷價(jià)值。 方法 選擇2018年1月～2019年6月浙江省寧波市康寧醫(yī)院（以下簡稱“我院”）情感障礙科收治的100例抑郁癥患者作為抑郁癥組，另選擇同期在我院進(jìn)行常規(guī)體檢的60名健康人群作為對照組。比較兩組患者以及不同嚴(yán)重程度的抑郁癥患者GDNF表達(dá)情況及血清NLRP3炎癥小體水平，分析抑郁嚴(yán)重程度與GDNF、血清NLRP3炎癥小體水平的相關(guān)性，計(jì)算GDNF、NLRP3炎癥小體單項(xiàng)檢測以及聯(lián)合檢測在診斷抑郁癥中的診斷效能。 結(jié)果 抑郁癥組GDNF水平明顯低于對于對照組，血清NLRP3炎癥小體水平明顯高于對照組，差異均有統(tǒng)計(jì)學(xué)意義（均P < 0.05）。不同嚴(yán)重程度抑郁癥患者的GDNF及NLRP3炎癥小體水平比較，差異有統(tǒng)計(jì)學(xué)意義（P < 0.05）。與輕度抑郁組比較，中度抑郁組、重度抑郁組GDNF水平降低、NLRP3炎癥小體水平升高，差異均有統(tǒng)計(jì)學(xué)意義（均P < 0.05），與中度抑郁組比較，重度抑郁組GDNF水平降低、NLRP3炎癥小體水平升高，差異均有統(tǒng)計(jì)學(xué)意義（均P < 0.05）。GDNF表達(dá)水平與抑郁癥嚴(yán)重程度均呈負(fù)相關(guān)（r = -0.603，P < 0.05），血清NLRP3炎癥小體表達(dá)水平與抑郁癥嚴(yán)重程度均呈正相關(guān)（r = 0.762，P < 0.05）。GDNF、NLRP3炎癥小體聯(lián)合檢測診斷抑郁癥的敏感度和特異度明顯高于GDNF、NLRP3炎癥小體單項(xiàng)檢測，且有較好的特異度。結(jié)論 GDNF及血清NLRP3炎癥小體的異常表達(dá)與抑郁癥的發(fā)生、發(fā)展密切相關(guān)，GDNF、NLRP3炎癥小體聯(lián)合檢測有助于抑郁癥診斷和病情評估。

[關(guān)鍵詞] 抑郁癥;膠質(zhì)細(xì)胞源性神經(jīng)營養(yǎng)因子;Nod樣受體蛋白3炎癥小體;診斷價(jià)值

[中圖分類號] R651.2? ? ? ? ? [文獻(xiàn)標(biāo)識碼] A? ? ? ? ? [文章編號] 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炎癥小體功能失調(diào)可導(dǎo)致免疫系統(tǒng)炎癥的激活從而參與抑郁癥的發(fā)生發(fā)展[23-24]。本研究結(jié)果顯示，抑郁癥患者血清NLRP3炎癥小體水平明顯高于健康人群，且NLRP3炎癥小體的水平隨著抑郁程度的增加而升高。提示NLRP3炎癥小體與抑郁癥的發(fā)生發(fā)展有關(guān)。血清NLRP3炎癥小體隨著抑郁程度的加重而增加，可將其作為評估抑郁癥嚴(yán)重程度的客觀指標(biāo)。

單項(xiàng)檢測NRLP3炎癥小體，GDNF對診斷抑郁癥有一定效能，但靈敏度不高，特異度不強(qiáng)，臨床應(yīng)用價(jià)值受限。兩指標(biāo)的聯(lián)合檢測診斷抑郁癥時(shí)AUC、靈敏度及特異度均高于單項(xiàng)檢測。提示聯(lián)合檢測NRLP3炎癥小體，GDNF有利于提高抑郁癥的診斷能力。Pearson相關(guān)分析發(fā)現(xiàn)，GDNF表達(dá)與抑郁癥嚴(yán)重程度呈負(fù)相關(guān)。NLRP3炎癥小體水平與抑郁癥嚴(yán)重程度呈正相關(guān)。GDNF及NLRP3炎癥小體水平可作為診斷、評估抑郁癥癥狀程度的可靠指標(biāo)。

綜上所述，抑郁癥發(fā)生時(shí)患者GDNF表達(dá)下降，NLRP3炎癥小體表達(dá)異常升高。GDNF、NLRP3炎癥小體可能參與了抑郁癥的發(fā)生發(fā)展。GDNF、NLRP3炎癥小體聯(lián)合檢測可作為參考指標(biāo)用于抑郁癥的診斷和病情評估。

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（收稿日期：2019-09-24? 本文編輯：劉永巧）