γδTCR受体拮抗剂部分缓解C57BL/6小鼠抑郁症状的作用机制研究

Mechanism of action of the γδTCR receptor antagonist on the partial remission of depression in C57BL/6 mice

目的研究γδT细胞在慢性应激诱发抑郁行为中的免疫炎性机制。方法按照随机数表法将C57BL/6小鼠分为4组,每组20只:正常组、对照组、模型组和实验组。后3组按照慢性温和不可预知性刺激程序建立抑郁行为小鼠模型,为期4周。同时对照组和实验组每天分别经腹腔注射氟西汀溶液10mg·kg^(-1)和γδTCR的单克隆抗体(UC7-13D5)250μg,正常组和模型组经腹腔注射等体积0.9%Na Cl。4周后,进行糖水偏好实验和强迫游泳实验,用Bioplex检测系统测定外周血和脑组织内的肿瘤坏死因子-α(TNF-α)水平。结果 4周后,正常组、对照组、模型组和实验组的糖水偏好百分比分别为(56.30±1.03)%,(56.37±1.20)%,(46.90±1.45)%,(54.65±1.88)%,模型组与正常组比较,差异有统计学意义(P<0.01);实验组与模型组相比,差异有统计学意义(P<0.01)。这4组的血浆TNF-α浓度分别为(11.61±0.59),(11.99±1.19),(80.31±2.32),(12.14±0.84)pg·m L^(-1),模型组和正常组相比,差异有有统计学意义(P<0.01);对照组和实验组与模型组相比,差异均有统计学意义(均P<0.01)。这4组的皮质TNF-α浓度为(64.66±0.49),(67.26±1.22),(120.79±0.99),(79.87±0.49)pg·m L^(-1)。模型组和正常组相比,差异有有统计学意义(P<0.01);对照组和实验组与模型组相比,差异均有统计学意义(均P<0.01)。结论慢性应激可以通过炎性反应诱导抑郁行为的发生,UC7-13D5可以通过阻断γδT细胞分泌细胞因子部分缓解抑郁症状。

Objective To study the immune inflammatory mechanism ofγδT cells in depressive behaviors induced by chronic stress. Methods Adult health C57 BL/6 mouse were randomly divided into 4 groups：normal group,control group,model group and experimental group. The mouse in last three group were receiving chronic unpredictable mild stimulations to build depressive behavior in mice model. Meanwhile,the fluoxetine solutions 10 mg · kg-1 were injected intraperitoneally in the control group everyday,and the γδTCR polyclonal antibody（ UC7-13 D5） 250 μg were injected intraperitoneally in the experimental group respectively. Normal group and model group received intraperitoneal injection of the same volume of normal saline. After the chronic unpredictable mild stimulate for 4 weeks,the sugar water preference test and forced swimming test compared between 4 groups,the concentration oftumor necrosis factors-α（ TNF-α） in both peripheral blood and brain tissue are measured by Bio-plex detection system. Results After 4 weeks administration,the sugar water preference in the normal group,control group,model group and experimental group were（ 56. 30 ± 1. 03） %,（ 56. 37 ± 1. 20） %,（ 46. 90 ± 1. 45） %,（ 54. 65 ± 1. 88） %;comparison between model group and normal group,the difference had significantly（ P〈0. 01）; comparison between experimental group and model group,the difference had significantly（ P〈0. 01）. The plasma concetration of TNF-α in the 4 groups were（ 11. 61 ± 0. 59）,（ 11. 99 ± 1. 19）,（ 80. 31 ± 2. 32）,（ 12. 14 ± 0. 84） pg·m L-1; the cortical concetration of TNF-α in the 4 groups were（ 64. 66 ± 0. 49）,（ 67. 26 ± 1. 22）,（ 120. 79 ± 0. 99）,（ 79. 87 ± 0. 49）pg·m L-1; comparison between model group and normal group,the difference had significantly（ all P〈0. 01）; comparison between experimental group with model group,the difference had significantly（ all P〈0. 01）. Conclusion Chronic stress can induce depressive behavior by inflammatory reaction,UC7-13 D5 can partially alleviate symptoms of depression by blocking γδT cells secreted cytokines.