CXCL5基因敲除小鼠抑郁样行为及血清TNF-α、IL-1β、IL-6水平变化  

Depressive-like behaviors and serum TNF-α,IL-1β and IL-6 levels in CXCL5 gene knockout mice

作　　者：袁东亮 权伟[3] 陈奕晨 龚阳泽 刘凌之 邵青 翟媛媛[3] 赵正杭[1] YUAN Dongliang;QUAN Wei;CHEN Yichen;GONG Yangze;LIU Lingzhi;SHAO Qing;ZHAI Yuanyuan;ZHAO Zhenghang(School of Basic Medicine,Xi'an Jiaotong University,Xi'an 710061,China;不详)

机构地区：[1]西安交通大学基础医学院,西安710061 [2]空军军医大学唐都医院药剂科 [3]西安市精神卫生中心药剂科

出　　处：《山东医药》2022年第14期46-49,共4页Shandong Medical Journal

基　　金：陕西省自然科学基础研究计划项目(2020JM-701);陕西省西安市科技局医学项目(2019115113YX006SF039-11)。

摘　　要：目的观察CXC趋化因子配体5(CXCL5)基因敲除小鼠与野生型小鼠抑郁样行为和血清炎症因子TNF-α、IL-1β、IL-6水平的差异。方法取CXCL5+/-杂合子小鼠4只、C57野生型小鼠16只,雌雄各半。将CXCL5+/-杂合子小鼠雌雄配对进行繁殖,剪取子代鼠尾,提取基因组DNA,用qRT-PCR法鉴定子代小鼠的基因型,取CXCL5^(-/-)纯合子小鼠继续繁殖,直至获得30只CXCL5^(-/-)小鼠,其中雌性16只、雄性14只。取CXCL5^(-/-)纯合子小鼠和野生型小鼠各8只,雌雄各半,称取4、6、8、10周龄小鼠的体质量;取10周龄CXCL5^(-/-)纯合子小鼠和野生型小鼠各8只,以慢性不可预见性的温和刺激(CUMS)配合孤养来建立抑郁症模型,以小鼠出现自主活动明显减少为造模成功。采用强迫游泳实验和悬尾不动实验对小鼠进行抑郁症行为学评估;取小鼠腹主动脉血,检测血清TNF-α、IL-1β、IL-6水平。结果雄性及雌性CXCL5^(-/-)小鼠在4、6、8、10周龄时的体质量与同龄、同性别野生型小鼠比较,差异均无统计学意义(P均>0.05)。与野生型抑郁症小鼠比较,CXCL5^(-/-)抑郁症小鼠强迫游泳及悬尾不动时间均缩短,血清TNF-α、IL-1β、IL-6水平均降低(P均<0.05)。结论CXCL5基因敲除能够阻断小鼠的抑郁样行为,其机制可能与抑制炎症反应有关。Objective To observe the differences in depressive-like behaviors and serum levels of inflammatory factors tumor necrosis factor-α(TNF-α),interlukin-1β(IL-1β)and IL-6 between CXC chemokine ligand 5(CXCL5)gene knockout mice and wild-type mice.Methods Four heterozygous mice(CXCL5+/-)and 16 C57 mice(wild-type)were selected.Half of them were female and half were male.The male and female CXCL5+/-heterozygous mice were paired for breeding,the tails of the offspring were clipped,the genomic DNA was extracted,and the genotype of the offspring mice was identified by qRT-PCR.CXCL5^(-/-)homozygous mice were continued to breed until 30 CXCL5^(-/-)mice were obtained,including 16 females and 14 males.Eight homozygous mice(CXCL5^(-/-))and eight wild-type C57 mice were selected,and half of them were female and half were male.We weighed the body weight of 4-,6-,8-,and 10-week-old mice.Eight 10-week-old homozygous mice(CXCL5^(-/-))and eight wild-type mice were selected,and the depression model was established by chronic unpredictable mild stimulation(CUMS)combined with orphanage.The models were successfully established with the manifestation of obvious reduction of autonomous activity.Forced swimming test and tail suspension test were used to evaluate the behavior of depression in mice.Serum levels of TNF-α,IL-1β,and IL-6 were detected in the blood from aorta abdominalis in mice.Results There was no significant difference in body weight at 4,6,8,and 10 weeks of age between CXCL5^(-/-)mice and wild-type mice of the same age and sex(all P>0.05).Compared with wild-type mice,CXCL5^(-/-)mice had shorter immobility time in the forced swimming test and the tail suspension test,and lower serum levels of TNF-α,IL-1β,and IL-6(all P<0.05).Conclusion CXCL5 knockout can block depression-like behavior in mice,and the mechanism may be related to the inhibition of inflammatory response.

关 键 词：趋化因子配体5基因 基因敲除 抑郁症模型 慢性不可预见性的温和刺激 动物实验 

分 类 号：R749.4[医药卫生—神经病学与精神病学]