分泌脂质蛋白-2激活小胶质细胞对大鼠抑郁症发病机制的影响

发布时间：2019-07-25 08:57

【摘要】：目的分泌脂质蛋白-2(Lipocalin-2,LCN2)能促进小胶质细胞的M1途径,文中旨在探讨LCN2通过激活小胶质细胞在大鼠抑郁症发病中的影响及其相关机制。方法根据慢性应激反应抑郁模型(Mitogen-activated protein kinase,UCMS),将40只成年雄性SD大鼠分成4组(n=10):正常对照组、UCMS组、UCMS+LCN2 SiRNA组、SiRNA对照组。对UCMS组和UCMS+LCN2 SiRNA组的大鼠进行21 d的应激刺激建立抑郁模型。从应激刺激第7天开始,UCMS+LCN2 SiRNA组和SiRNA对照组的大鼠腹腔注射0.4 mg的10%水合氯醛麻醉,并予0.015μL/g的LCN2 SiRNA,3次/周,鞘内注射,至应激结束时(21 d)停止。正常对照组,UCMS组在同一时间同样的方法给予相同体积的等渗盐水。测定大鼠的体重进行蔗糖偏爱实验、强迫游泳实验测行为学。取大鼠的海马,于实验开始时及开始后第3周分别用免疫荧光法和免疫印迹法测定小胶质细胞特异标记物Iba1和LCN2的表达情况。结果第3周时,UCMS+LCN2 SiRNA组大鼠体重高于UCMS组[(262.82±0.01)g vs(179.98±0.08)g,P0.05];正常对照组、SiRNA对照组大鼠体重较UCMS组、UCMS+LCN2 SiRNA组均升高(P0.05)。UCMS组大鼠的蔗糖偏爱值(0.25±0.04)较UCMS+LCN2 SiRNA组(0.81±0.01)、正常对照组(0.82±0.01)及SiRNA对照组(0.82±0.01)显著降低(P0.05)。UCMS+LCN2 SiRNA组的强迫游泳实验不动时间较UCMS组显著缩短[(4.64±0.8)s vs(23.11±2.63)s,P0.05]。UCMS组大鼠海马中的LCN2的表达量较其他3组明显升高(P0.05)。UCMS组大鼠海马中的Iba1较其他3组表达活跃。结论 LCN2与慢性应激反应诱导的抑郁症发病有关系,其机制可能与大鼠中枢系统中小胶质细胞的激活有关。
[Abstract]:Objective to promote the M1 pathway of microglia by secreting lipid protein-2 (Lipocalin-2,LCN2). The purpose of this study was to investigate the effect of LCN2 on the pathogenesis of depression in rats by activating microglia and its related mechanism. Methods according to the chronic stress response depression model (Mitogen-activated protein kinase,UCMS), 40 adult male SD rats were divided into 4 groups: normal control group, UCMS LCN2 SiRNA group and SiRNA control group. The depression model was established by stress stimulation in UCMS group and UCMS LCN2 SiRNA group for 21 days. From the 7th day after stress stimulation, the rats in UCMS LCN2 SiRNA group and SiRNA control group were anesthetized with 0.4 mg 10% chloral hydrate intraperitoneally, and were anesthetized with 0.015 渭 L / g LCN2 SiRNA,3 per week, intrathecal injection, and stopped at the end of stress (21 days). In the normal control group, UCMS group was given the same volume of isoosmotic saline at the same time. The body weight of rats was measured by sucrose preference test and forced swimming test to measure behavior. The expression of Iba1 and LCN2, the specific markers of microglia, were detected by immunofluorescence and immunoblotting at the beginning of the experiment and the third week after the beginning of the experiment. Results at the 3rd week, the body weight of rats in UCMS LCN2 SiRNA group was higher than that in UCMS group [(262.82 卤0.001) g vs (179.98 卤0.008) g, P 0.05]. The body weight of normal control group, SiRNA control group was higher than that of UCMS group and UCMS LCN2 SiRNA group (P 0.05). The sucrose preference value of). UCMS group (0.25 卤0.004) was higher than that of UCMS LCN2 SiRNA group (0.81 卤0.001). The immobility time of forced swimming in). UCMS LCN2 SiRNA group was significantly shorter than that in UCMS group [(4.64 卤0.8) s vs (23.11 卤2.63) s, P 0.05]. The expression of LCN2 in hippocampus of UCMS group was significantly higher than that of the other three groups (P 0.05). The expression of Iba1 in hippocampus of). UCMS group was significantly higher than that of the other three groups. Conclusion LCN2 is associated with depression induced by chronic stress response, and its mechanism may be related to the activation of microglia in the central system of rats.
【作者单位】：徐州医学院麻醉学重点实验室;南京军区南京总医院麻醉科;
【分类号】：R749.4

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