CAJ | 학술논문

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（an‐terior 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。
목적：통과비교불동면역상태적백세포분화항원38（cluster of differentiation ，CD38）기인고제소서화건강소서중추신경면역조절상관뇌구공능적차이，탐토 CD38의뢰적개리자신호재신경면역조절상관신호련중적작용。방법 CD38기인고제소서（모형조）화건강소서（대조조）각30지，수궤분성면역제0、2、4、6、8천조。응용면역조직화학기술검측실험각조동물하구뇌외측구（lateral hypothalamic area ，LH）화행인핵전구（an‐terior amygdaloid area ，AA）신경면역조절공능활화신호백세포개소‐1β（interleukin‐1β，IL‐1β）화백세포개소‐6（interleukin‐6，IL‐6）표체수평，ELISA 법검측각조동물외주혈청중 IL‐1β、IL‐6표체，분석 CD38결함대신경면역조절공능신호련적영향。결과재면역후0、2、4、6、8천각시간점，모형조소서 LH 화 AA 뇌구 IL‐1β표체〔분별위387.90（345.73，463.99）、757.80±86.05、708.83±87.56、531.55±70.85、585.66±52.47〕균교대조조〔분별위309.18（177.94，415.32）、300.02±52.79、332.61±82.10、330.20±37.20、256.17±86.04〕승고（P ＜0.05），모형조화대조조소서 LH 화 AA 뇌구 IL‐6표체비교，이급외주혈 IL‐1β화 IL‐6표체비교，차이균무통계학의의（P＞0.05）。결론 CD38적결실가능도치중추신경면역조절상관뇌구 IL‐1β표체승고，단대 IL‐6신호계통몰유명현영향，제시재 LH 화 AA 뇌구，CD38부삼여 IL‐1β신호련적부향조절。
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‐1β (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 .