大鼠抑郁障碍与心血管组织炎性标记物的相关性研究

Relationship between depressive disorder and inflammation markers in depression rat model

目的探讨强迫游泳抑郁模型大鼠抑郁障碍与炎性标记物的相关性。方法健康SD大鼠随机抽签分为对照组和模型组,应用21 d强迫游泳试验建立大鼠抑郁模型,模型组大鼠包括SS组(9只,应激+生理盐水腹腔注射)、SF组(8只,应激+氟西汀腹腔注射)和SI组(8只,应激+丙咪嗪腹腔注射)。对照组大鼠包括CS组(10只,生理盐水腹腔注射),CI组(7只,丙咪嗪腹腔注射)。应用透射免疫比浊法和酶联免疫法检测外周血炎性标记物高敏C反应蛋白(hsCRP)、单核细胞趋化因子1(MCP-1)水平,应用免疫组织化学染色法和蛋白印迹法检测血管组织核因子-κB(NF-κB)p65、抑制蛋白κB(IκB)-α、MCP-1表达水平。结果应激后模型组外周血hsCRP和MCP-1含量明显高于CS、CI组,SS组与CS组hsCRP水平分别为(0.26±0.07)mg/L和(0.15±0.06)mg/L(P<0.01),SS组与CS组MCP-1水平分别为(52.02±18.83)ng/L和(22.52±8.45)ng/L(P<0.01)。血管组织中MCP-1、NF-κB p65表达显著增强,SS组与CS组MCP-1水平分别为(1.78±0.36)mg/L和(0.85±0.15)mg/L,SS组与CS组NF-κB p65水平分别为(0.88±0.16)和(0.12±0.04)(P<0.01),胞浆中IκB-α表达显著减少,SS组与CS组IκB-α水平分别为(0.48±0.07)和(2.07±0.48)(P<0.01)。结论抑郁障碍通过NF-κB表达增强来启动炎症反应。

Objective To investigate the relationship between depressive disorder and inflammation markers in depression rat model. Methods Depression rat model was made by Forced Swimming Test （FST） in 21days. A total of 50 Sprague-Dawley rats were randomly divided into 5 groups： CS group （n = 10, control group, treated with saline）, CI group （n = 10, control group, treated with imipramine） , SS group （n = 10, model group, treated with saline）, SF group （n = 10, model group, treated with fluoxetine） and SI group （n = 10, model group, treated with imipramine）. Monocyte chemoattractant protein-1 （MCP- 1 ） in peripheral blood was measured by enzyme linked immunoassay （ELISA） and hypertensive C-reaction protein （hsCRP） by immunoturbidimetric assay. The expression of MCP-1, nuclear factor-kappa B （NF- KB） 1365 and inhibitory kappa B （IKB）-（x in aorta tissue were observed by immunohistochemistry and western blot. Results Eight rats died during the study （3 in CI group, 1 in SS group, 2 in SF group and 2 in SI group）. Serum concentration of hsCRP and MCP-1 in peripheral blood was significantly higher [ （0. 26 ± 0. 07） mg/L vs. （0. 15± 0. 06） mg/L for hsCRP and （52. 02 ± 18.83 ） ng/L vs. （22. 52± 8.45 ） ng/L for MCP-1, both P 〈 0. 01 ] and expression of MCP-1 and NF-KB p65 in aorta tissue was significantly increased in SS group than in CS group [ （1.78 ± 0. 36） vs. （0. 85 ±0. 15 ） for MCP-1 and （0. 88 ± 0. 16） vs. （0. 12 ± 0. 04） for NF-KB 1365, both P 〈 0. 01 ]. The expression of IKB-α was significantly decreased in aorta tissue in SS group than in CS group [ （0.48±0. 07） vs. （2. 07±0.48）, P 〈0. 01 ]. Conclusions Depression disorder activates inflammatory reaction by increasing expression of NF-KB.