二甲双胍对大鼠抑郁样行为的作用及机制研究  

Effect and mechanism of metformin on depression-like behavior in rats

作　　者：马瑞[1] 古力巴克然木·阿布拉[1] 张义[1] 邹韶红[1] 贾仁 Ma Rui;Guli Rakranmu·Abra;Zhang Yi;Zou Shaohong;Jia Ren(Department of Clinical Psychology,Peopled Hospital of Xinjiang Uygur Autonomous Region,llrumqi 830001,China)

机构地区：[1]新疆维吾尔自治区人民医院临床心理科,乌鲁木齐830001 [2]新疆医科大学基础医学院

出　　处：《脑与神经疾病杂志》2021年第10期634-639,共6页Journal of Brain and Nervous Diseases

基　　金：2019D01C007。

摘　　要：目的研究二甲双胍对大鼠抑郁样行为的影响,并初步探究其作用机制。方法将55只SD雄性成年大鼠随机分为5组(每组11只):A组为正常大鼠,B-E组为模型大鼠,大鼠抑郁模型采用慢性不可预见性应激(CUS)方法28天建立。建模完成后,C-E组大鼠分别给予30 mg·kg^(-1)、90 mg·kg^(-1)、300 mg·kg^(-1)二甲双胍生理盐水溶液d-1×7腹腔注射,A组和B组大鼠均给予等量生理盐水d-1×7腹腔注射。给药结束后分别进行大鼠体重、糖水偏好、旷场实验和强迫游泳检测,最后用荧光定量PCR和蛋白印迹法评价5组大鼠脑组织中核因子κB(NF-κB)和白介素-6(IL-6)的mRNA和蛋白表达水平。结果与A组正常大鼠相比,B组CUS大鼠的糖水偏爱值明显降低,旷场运动总距离(自发活动)明显减少,强迫游泳不动时间(绝望无助)显著增加,说明CUS大鼠抑郁模型建立成功。与B组相比,二甲双胍对大鼠抑郁行为均有不同程度的影响,其中D组(90 mg·kg^(-1)二甲双胍)大鼠的质量增长、糖水偏爱值、旷场中自发活动和强迫游泳不动时间变化最为明显(P<0.05),且测试值与A组相近。此外,CUS大鼠(B组)脑组织中NF-κB和IL-6表达水平明显较A组增加。用二甲双胍处理CUS大鼠后,其脑组织中NF-κB和IL-6表达水平明显降低(P<0.05),尤其D组最为明显。结论二甲双胍(用药量为90 mg·kg^(-1))对CUS大鼠的抑郁样行为具有明显改善作用,且作用机理可能是通过抑制炎性因子NF-κB和IL-6表达而实现的,说明其具有治疗抑郁症患者的临床应用潜力。Objective To study the effect of metformin on depression-like behavior in rats and explore its mechanism.Methods 55 SD male adult rats were randomly divided into 5 groups(11 rats in each group):normal rats in group A and model rats,which were stimulated with chronic unpredictability stress(CUS)method for 28 days,in group B-E.After the completion of modeling,rats in C-E group were given intraperitoneal injection of metformin saline solution at 30 mg·kg^(-1),90 mg·kg^(-1) and 300 mg·kg^(-1) respectively,while rats in group A and group B were given intraperitoneal injection of the same amount of normal saline solution.Give the medicine once a day for 8 days.At the end of administration,body weight,preference for sugar water,field experiment and forced swimming were measured,and the mRNA and protein expression levels of nuclear factor kappa-B(NF-κB)and interleukin-6(IL-6)in the rat brain tissues of the 5 groups were evaluated by fluorescence quantitative PCR and western blotting.Results Compared with normal rats in group A,CUS rats in group B showed slow weight growth,reduced sugar water preference,reduced total distance(spontaneous activity),and increased time of forced swimming immobility(hopelessness).The differences were statistically significant(P<0.05).These results indicate that CUS rats’depression model was successfully established.Compared with group B,metformin had different effects on weight and depressive behaviors in rats,among which group D(90 mg·kg^(-1) metformin)had the most obvious changes in weight gain,sugar water preference value,spontaneous activity in the field and immobilization time of forced swimming(P<0.05),and the test value was similar to that of group A.Moreover,the expression levels of NF-κB and IL-6 in the rat brain tissues of CUS rats(group B)were significantly increased compared with those of group A,suggesting that depression-like behaviors might be related to inflammation.After treatment with metformin,the expression levels of NF-κB and IL-6 in the brain tissues of GUS rats

关 键 词：二甲双胍 慢性不可预见性应激 抑郁 炎症 腺苷酸活化蛋白激酶 

分 类 号：R741[医药卫生—神经病学与精神病学]