Toll样受体2抑制剂C29的抗抑郁效应及其机制  

Study on antidepressant effect of Toll-like receptor 2 inhibitor C29 and its mechanism

作　　者：靳玫[1] 崔俊伟[2] 刘晓利[3] 宿俊杰[3] 王文晟[2] 

机构地区：[1]新乡医学院第三附属医院神经内科,河南新乡453003 [2]新乡医学院第一附属医院结核病研究所,河南卫辉453100 [3]河南师范大学生命科学学院,河南新乡453007

出　　处：《新乡医学院学报》2017年第6期460-464,共5页Journal of Xinxiang Medical University

基　　金：国家自然科学基金面上项目(编号:31170733);河南省自然科学基金资助项目(编号:162300410217)

摘　　要：目的探讨Toll样受体2(TLR2)抑制剂C29对抑郁症状的作用和机制。方法将40只小鼠随机分为正常组、正常+抑制剂组、抑郁组和抑郁+抑制剂组,每组10只。将抑郁组和抑郁+抑制剂组小鼠采用慢性不可预见性中等强度应激+孤养的方法建立抑郁模型。正常组和抑郁组小鼠用不含C29的5 g·L^(-1)羧甲基纤维素钠溶液进行灌胃,正常+抑制剂组和抑郁+抑制剂组小鼠用含C29的5 g·L^(-1)羧甲基纤维素钠溶液进行灌胃,每2 d 1次,持续21 d。模型制作后观察各组小鼠强迫游泳不动时间和糖水消耗情况并进行比较;用免疫荧光染色和流式细胞仪分析小鼠大脑中神经元核抗原(Neu N)、Ki-67、CD3和F4/80阳性细胞的变化,实时定量聚合酶链式反应检测TLR2在小鼠大脑组织中的表达。结果正常组、抑郁组、正常+抑制剂组和抑郁+抑制剂组小鼠强迫游泳不动时间分别为(71.23±17.16)、(131.76±35.15)、(76.26±26.44)和(84.48±23.73)s,抑郁组小鼠强迫游泳不动时间显著长于正常组、正常+抑制剂组和抑郁+抑制剂组(P<0.05),正常组、正常+抑制剂组和抑郁+抑制剂组小鼠强迫游泳不动时间两两比较差异均无统计学意义(P>0.05);抑郁组小鼠的糖水偏好为(45.3±13.7)%,显著低于正常组小鼠的(74.5±18.7)%(P<0.05);应用C29后,正常+抑制剂组小鼠的糖水偏好为(77.1±17.6)%,抑郁+抑制剂组小鼠的糖水偏好为(67.9±19.5)%,均显著高于抑郁组(P<0.05)。抑郁组、抑郁+抑制剂组小鼠大脑组织中TLR2表达较正常组和正常+抑制剂组显著增加;正常组与正常+抑制剂组、抑郁组与抑郁+抑制剂组小鼠大脑组织中TLR2表达比较差异均无统计学意义(P>0.05)。流式细胞仪分析结果显示,4组小鼠大脑组织中Neu N、Ki-67阳性细胞所占比例两两比较差异均无统计学意义(P>0.05);抑郁组小鼠大脑中CD3阳性T淋巴细胞、F4/80阳性巨噬细胞的比例较正常组、正常+抑制剂组、抑郁+抑Objective To explore the effect and mechanism of Toll-like receptor 2 （TLR2） inhibitor C29 on depressive diseases.Methods Forty mice were randomly divided into normal group,normal ＋ inhibitor group,depression group and depression ＋ inhibitor group,with 10 mice in each group.Moderate chronic unpredictable stress （CUMS） ＋ solitary ways was used to establish the depression model in the mice of depression group and depression ＋ inhibitor group.The mice in normal group and depression group were treated with 5 g · L-1 sodium carboxymethyl cellulose solution without C29 via gavage.The mice in normal ＋ inhibitor group and depression ＋ inhibitor group were treated with 5 g · L-1 sodium carboxymethyl cellulose containing C29 via gavage.Treatment was performed once every other day for 21 days.The immobility time of forced swimming and sucrose preference of mice after treatment were observed.Immunofluorescent staining and flow cytometry were used to analyze the changes of neuronal nuclei（NeuN）,Ki-67,CD3 and F4/80 positive cell distribution in the brain of mice.The expression of TLR2 in brain tissues was detected by real-time polymerase chain reaction.Results The immobility time of forced swimming of mice in the normal group,depression group,normal ＋ depression group and depression ＋ inhibitor group was （71.23 ± 17.16）,（131.76 ± 35.15）,（76.26 ± 26.44） and （84.48 ± 23.73） s respectively.The immobility time of forced swimming of mice in the depression group was significantly longer than that in the normal group,normal ＋ inhibitor group and depression ＋ inhibitor group （P 〈 0.05）;there was no significant difference in immobility time of forced swimming of mice among the normal group,normal ＋ inhibitor group and depression ＋ inhibitor group （P 〉 0.05）.Sucrose preference of the mice in the depression group [（45.3 ± 13.7） %] was significantly lower than that in the normal group [（74.5 ± 18.7） %] （P 〈 0.05）.After treatment with C29,the sucrose pref

关 键 词：TOLL样受体2 Toll样受体2抑制剂 大脑 炎症 免疫细胞 

分 类 号：R749.5[医药卫生—神经病学与精神病学]