目的通过比较不同免疫状态的白细胞分化抗原38(cluster of differentiation,CD38)基因敲除小鼠和健康小鼠中枢神经免疫调节相关脑区功能的差异,探讨CD38依赖的钙离子信号在神经免疫调节相关信号链中的作用。方法 CD38基因敲除小鼠(模型组)和健康小鼠(对照组)各30只,随机分成免疫第0、2、4、6、8天组。应用免疫组织化学技术检测实验各组动物下丘脑外侧区(lateral hypothalamic area,LH)和杏仁核前区(anterior amygdaloid area,AA)神经免疫调节功能活化信号白细胞介素-1β(interleukin-1β,IL-1β)和白细胞介素-6(interleukin-6,IL-6)表达水平,ELISA法检测各组动物外周血清中IL-1β、IL-6表达,分析CD38缺陷对神经免疫调节功能信号链的影响。结果在免疫后0、2、4、6、8天各时间点,模型组小鼠LH和AA脑区IL-1β表达〔分别为387.90(345.73,463.99)、757.80±86.05、708.83±87.56、531.55±70.85、585.66±52.47〕均较对照组〔分别为309.18(177.94,415.32)、300.02±52.79、332.61±82.10、330.20±37.20、256.17±86.04〕升高(P〈0.05),模型组和对照组小鼠LH和AA脑区IL-6表达比较,以及外周血IL-1β和IL-6表达比较,差异均无统计学意义(P〉0.05)。结论 CD38的缺失可能导致中枢神经免疫调节相关脑区IL-1β表达升高,但对IL-6信号系统没有明显影响,提示在LH和AA脑区,CD38仅参与IL-1β信号链的负向调节。
Objective Explore the role of CD38 dependent calcium signal pathway in neuroimmunoregulation associated signal chain through comparing functional differences in neuroimmunoregulation related brain areas between wild type mice and CD38 knockout mice at different immune states. Methods Thirty wild type mice and thirty CD38 knockout mice were randomly divided into unimmune group and immune 2, 4, 6, 8 days' groups (6 cases in each group). To analyze the influence of CD38 deficiency on neuroimmunoregulation function, immunohistochemistry was used to test levels of interleukin-lβ (IL-1β) and interleukin-6 (IL-6) in lateral hypothalamic (LH) area and anterior amygdaloid (AA) area, which are neuroimmunoregulation related cerebral regions. IL-1β and IL-6 expression in periphery serum were tested by ELISA. Results In immune 0, 2, 4, 6, 8 days' groups, IL-1β expression in LH area and AA area of CD38 knockout mice [387.90 (345.73, 463.99), 757.80±86.05, 708.83±87.56, 531.55±70.85, 585.66±52.47] were higher than that of wild type mice [309.18 (177.94, 415.32), 300.02±52.79, 332.61±82.10, 330.20 ±37.20, 256.17±86.04] with statistical significance (P〈0.05). IL-6 expression in LH and AA between CD38 knockout mice and wild type mice showed no significant difference (P〉0. 05). In immune 0, 2, 4, 6, 8 days' groups, IL-1β and IL 6 expressions in peripheral serum between CD38 knockout mice and wild type mice showed no significant difference (P 〉 0.05). Conclusions Blocking CD38 can increase IL-1β expression in neuroimmunomodulation related brain regions, but have little effect on IL-6 signal system. This suggested that CD38 can negatively regulate IL-1β signal pathway in LH and AA.