目的:探讨重复经颅磁刺激(repetitive transcranial magnetic stimulation，rTMS)对慢性不可预见应激(chronic unpredictable stress，CUS)大鼠抑郁样行为及海马脂质的影响。方法:将24只SD大鼠按照随机数字表法分为对照组(sham组)、模型组(CUS组)和rTMS治疗组(CUS ＋ rTMS组)，每组8只。适应性饲养7 d后，CUS组和CUS ＋ rTMS组大鼠接受为期28 d的CUS造模。造模结束后，CUS ＋ rTMS组大鼠接受rTMS干预7 d(5 Hz，1.26 Tesla)，sham组和CUS组大鼠接受假rTMS干预7 d。干预结束24 h后进行糖水偏好实验、旷场实验和强迫游泳实验检测大鼠的抑郁样行为；随后处死动物，收取海马组织，通过高效液相色谱-质谱联用技术检测脂质变化，采用Lipid Search software version 4.1和SIMCA-P 14.1软件分析脂质相对含量。采用SPSS 19.0进行统计分析，多组间比较采用单因素方差分析，两两比较采用Tukey检验。结果:(1)3组大鼠旷场实验、糖水偏好实验和强迫游泳实验的结果均差异有统计学意义(n F＝6.853～7.466，均n P<0.05)。在旷场实验中，CUS组大鼠[(50.72±6.38)s，(11.41±1.55)%]在旷场中央区的探索时间和中央区运动距离百分比明显少于sham组[(86.06±7.31)s，(18.60±1.21)%]和CUS ＋ rTMS组[(79.87±7.87)s，(16.74±1.27)%](均n P<0.05)；糖水偏好实验中，CUS组[(37.63±6.06)%]大鼠糖水摄取百分比明显少于sham组[(68.30±6.39)%]和CUS ＋ rTMS组[(62.68±5.50)%](均n P<0.05)；强迫游泳实验中，CUS组[(137.60±13.36) s]大鼠不动时间明显多于sham组[(80.57±10.36 )s]和CUS ＋ rTMS组[(86.14±11.49)s](均n P<0.05)。(2)3组大鼠海马脂质水平差异有统计学意义(n F＝3.826～15.440，均n P<0.05)。与sham组[(20 850.00±956.56)×10n 7，(788.78±136.11)×10n 7，(340.29±35.66)×10n 7，(239.65±18.14) ×10n 7，(22.96±4.04)×10n 7，(3.35±0.85)×10n 7，(6.71±0.82) ×10n 7，(424.52±33.38)×10n 7，(2.68±0.33)×10n 7]相比，CUS组[(24 133.33±1 242.04)×10n 7，(953.65±131.26)×10n 7，(275.32±35.78)×10n 7，(293.82±38.28) ×10n 7，(15.36±3.87)×10n 7，(4.57±1.02)×10n 7，(7.94±0.91) ×10n 7，(509.22±42.09)×10n 7，(3.39±0.33)×10n 7]大鼠海马的磷脂酰乙醇胺(phosphatidylethanolamine，PE)，磷脂酰肌醇(phosphatidylinositol，PI)，溶血卵磷脂(lysophosphatidylcholine, LPC)，磷酸肌酸(ceramide phosphates，CerP)，鞘氨醇(sphingosine，So)，甘油二酯(diglyceride，DG)和单甘油酯(monoglyceride，MG)等7类脂质分子在大鼠海马中的相对含量增加(均n P<0.05)，磷脂酸(phosphatidic acid，PA)和酰基肉碱(acyl carnitine，AcCa)相对含量减少(均n P<0.05)。rTMS治疗有效逆转了CUS导致的大鼠海马脂质水平改变，与CUS组相比，CUS ＋ rTMS组[(21 816.67±928.26)×10n 7，(783.16 ±91.52)×10n 7，(323.59±33.91)×10n 7，(236.39±32.02)×10n 7，(23.35±4.46)×10n 7，(3.16±0.85)×10n 7，(7.03±0.26)×10n 7，(421.55±44.28)×10n 7，(2.56±0.32)×10n 7]大鼠海马的PE，PI，LPC，CerP，So，DG和MG含量降低，PA和AcCa脂质含量升高(均n P<0.05)。n 结论:CUS模型大鼠海马的甘油磷脂、甘油糖脂、鞘脂、脂肪酸等多种脂质水平异常，而5 Hz的rTMS干预可以改善CUS模型大鼠的抑郁样行为和海马脂质紊乱。“,”Objective:To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the hippocampal lipidome in a rat model of chronic unpredictable stress(CUS).Methods:Twenty-four SD rats were randomly assigned to the following 3 groups (n n=8 for each group): sham group, CUS group and CUS+ rTMS group. The sham group received only sham stimulation and rats in the CUS and CUS+ rTMS group were subjected to CUS stimulation. Then, rats received 5 Hz rTMS (5 Hz, 1.26 Tesla) or sham rTMS for 7 days. After the last stimulation, all rats underwent sucrose preference test, open filed test and forced swimming test so as to observe the effect of rTMS on depressive behavior. Then, rats were sacrificed, and the levels of lipid composition in hippocampus were determined by high performance liquid chromatography mass spectrometry and analyzed by lipid search software version 4.1 and SIMCA-P 14.1.The software of SPSS 19.0 was used for statistical analysis. Univariate analysis of variance was used for comparison among groups, and Tukey test was used for multiple comparison.n Results:(1)There were significant differences in open field test, sugar preference test and forced swimming test among the three groups(n F=6.853-7.466, all n P<0.05). In the open field experiment, the exploring time and percentage of movement distance in central area of rats in CUS group((50.72±6.38)s, (11.41±1.55)%) was significantly less than that of sham group ((86.06±7.31)s, (18.60±1.21)%) and CUS+ rTMS group((79.87±7.87)s, (16.74±1.27)%)(alln P<0.05). The results of sucrose preference test showed that the percentage of sucrose intake of rats in CUS group ((37.63±6.06)%) was significantly lower than that in sham group ((68.30±6.39)%) and CUS+ rTMS group ((62.68±5.50)%)(bothn P<0.05) . In forced swimming test, the immobility time of rats in CUS group ((137.60±13.36)s) was significantly longer than that of sham group ((80.57±10.36)s)) and CUS+ rTMS group ((86.14±11.49)s) (bothn P<0.05). (2)The levels of lipid composition in hippocampus were significantly different in the three groups(n F=3.826-15.440, all n P<0.05). The contents of phosphatidylethanolamine (PE) ((20 850±956.56)×10n 7, (24 133.33±1 242.04)×10n 7), phosphatidylinositol (PI) ((788.78±136.11)×10n 7, (953.65±131.26)×10n 7), lysophosphatidylcholine (LPC) ((340.29±35.66)×10n 7, (275.32±35.78)×10n 7), creatine phosphate (CerP) ((239.65±18.14)×10n 7, (293.82±38.28)×10n 7), sphingosine (So) ((22.96±4.04)×10n 7, (15.36±3.87)×10n 7), diglyceride (DG) ((3.35±0.85)×10n 7, (4.57±1.02)×10n 7) and monoglyceride (MG) ((6.71±0.82)×10n 7, (7.94±0.91)×10n 7)in hippocampus of rats in CUS group were significantly higher than those of sham group(all n P<0.05), while the phosphatidic acid(PA) ((424.52±33.38)×10n 7, (509.22±42.09)×10n 7) and acyl carnitine(AcCa) ((2.68±0.33)×10n 7, (3.39±0.33)×10n 7) decreased(both n P<0.05). Compared with CUS group, the contents of PE(21 816.67±928.26)×10n 7, PI(83.16±91.52)×10n 7, LPC(323.59±33.91)×10n 7, CerP(236.39±32.02)×10n 7, So(23.35±4.46)×10n 7, DG(3.16±0.85)×10n 7 and MG(7.03±0.26)×10n 7 in the hippocampus of CuS+ rTMS group decreased, while the contents of PA(421.55±44.28)×10n 7 and ACCA(2.56±0.32)×10n 7 in the hippocampus of CUS+ rTMS group increased (all n P<0.05).n Conclusion:The levels of glycerophospholipids, glyceroglycerides, sphingolipids, fatty acids and other lipids in the hippocampus of CUS model rats are abnormal. And the 5 Hz rTMS intervention can ameliorate the depression like behavior and the disturbances of lipid in hippocampus of CUS model rats.