米诺环素对CCI大鼠抑郁样行为的影响及机制研究  

The effects of minocycline on depression-like behavior and its mechanism in CCI rats

作　　者：杨俊娜[1] 何丽[1] 徐陶[1] 杨帆[1] 徐瑞 许阿香 曾俊伟[1] Yang Junna;He Li;Xu Tao;Yang Fan;Xu Rui;Xu Axiang;Zeng Junwei(Department of Physiology,Zunyi Medical College,Guizhou Key Laboratory of Anesthesia and Organ Protection,Zunyi 563000,China)

机构地区：[1]遵义医学院生理学教研室贵州省麻醉与器官功能保护重点实验室,遵义563000

出　　处：《神经解剖学杂志》2019年第1期13-20,共8页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(Nos.31640040;31860291);贵州省教育厅创新群体重大研究项目(黔教合KY字[2018]045)

摘　　要：目的:观察海马CA1区注射米诺环素对坐骨神经慢性缩窄性损伤(CCI)大鼠的抑郁样行为、海马和前额叶皮层小胶质细胞激活的影响并分析其机制。方法:成年SD雄性大鼠随机分为:对照组、假手术组、CCI模型组、CCI+米诺环素组。糖水偏好及旷场实验检测大鼠抑郁样行为;免疫组化观察海马以及前额叶皮层Iba-1表达;取海马以及前额叶皮层组织,real-time PCR观察Iba-1、NLRP3和caspase1 mRNA表达,ELISA测定IL-1β和IL-18含量。结果:与假手术组相比,CCI大鼠7、10 d和14 d的糖水偏好明显降低(P <0. 05),旷场中央活动距离和中央活动时间明显减少(P <0. 05);与CCI组相比,CA1区注射米诺环素后CCI大鼠7 d和14 d的糖水偏好明显升高(P <0. 05),旷场中央活动距离和中央活动时间明显增加(P <0. 05)。与假手术组相比,CCI组大鼠海马CA1、CA3及DG区和前额叶皮层Iba-1阳性细胞数目显著增多(P <0. 05),Iba-1、NLRP3和caspase1 mRNA表达明显上调; IL-1β和IL-18含量也明显升高(P <0. 05)。与CCI组相比,注射米诺环素后,CCI大鼠海马CA1、CA3及DG区和前额叶皮层Iba-1阳性细胞数目减少(P <0. 05),Iba-1、NLRP3和caspase1 mRNA表达降低(P <0. 05),IL-1β和IL-18含量降低(P <0. 05)。结论:海马CA1区注射米诺环素明显抑制CCI大鼠的抑郁样行为;其机制可能是抑制海马和前额叶皮层小胶质细胞激活,下调NLRP3和caspase1表达,从而使IL-1β和IL-18产生减少。Objective:To investigate the effect of intra-CA1(cornu ammonis 1)administration of minocycline on the depressive-like behaviors and the activation of microglia in hippocampus and prefrontal cortex of rats with chronic constriction injury(CCI)of the sciatic nerve,and explored the possible mechanisms of CCI-induced depression-like behavior.Methods:Sprague-Dawley male rats were randomized into four groups:control group,sham group,CCI group,and CCI+minocycline group.The sucrose preference test and open field test were evaluated the depression-like behaviors.The expression of Iba-1 in the hippocampus and prefrontal cortex of the rat was detected by immunohistochemistry.The expression of Iba-1,NLRP3 and caspase1 mRNA in the hippocampus and prefrontal cortex were examined by RT-PCR.The content of IL-1βand IL-18 in the hippocampus and prefrontal cortex were examined by ELISA.Results:Compared with the sham group,the sucrose consumption test evaluatedat 7,10 and 14 days after surgery in the CCI model group decreased significantly(P<0.05)and the time and distances in the center zone in open field test was obviously decneas-ed(P<0.05).Compared with the CCI group,the sucrose consumption test was evaluatedat 7 and 14 days after surgery in rats with intra-CA1 injection of minocycline group increased significantly(P<0.05)and rats spent significantly more time and longer distances in the center zone(P<0.05).Numbers of Iba1-positive cells in CA1,CA3,DG and PFC were significantly increased in the CCI group compared to the sham group,and the numbers of Iba1-positive cells were significantly decreased after intra-CA1 injection of minocycline(P<0.05).The expression of Iba-1,NLRP3 and caspase1 mRNA in the hippocampus and prefrontal cortex was markedly enhanced after nerve injury(P<0.05).Compared with the CCI group,intra-CA1 injection of minocycline obviously suppressed the increased expression of Iba-1,NLRP3 and caspase1 mRNA(P<0.05).Compared with sham group,the content of IL-1βand IL-18 in the hippocampus and prefrontal cortex were

关 键 词：米诺环素 小胶质细胞 海马 前额叶皮层 抑郁样行为 大鼠 

分 类 号：R741[医药卫生—神经病学与精神病学]