强迫游泳应激对大鼠海马代谢物水平影响的在体研究

In vivo study of the impact of stress on metabolisms level of hippocampus in rats

目的探讨质子磁共振波谱（^1H-MRS）在体应激所致海马损伤的应用价值。方法将24只大鼠随机分为对照组（n=6）、单次应激组（n=6）、2周应激组（n=6）和4周应激组（n=6），利用强迫游泳试验（15min／d）建立应激动物模型，根据行为学和血清皮质酮水平评定应激效果，利用^1H-MRS测量大鼠双侧海马N-乙酰天冬氨酸／肌酸（NAA／Cr）和胆碱复合物／肌酸（Cho／Cr）比值。结果2周应激组血清皮质酮[（1001．36±82．84）ng／ml]明显高于对照组[（191．60±116．41）ng／ml]、单次应激组[（359．09±67．08）ng／ml]和4周应激组[（287．03±37．22）ng／ml]，P〈0.05。^1H-MRS在体检测结果显示2周应激组大鼠左侧海马NAA／Cr值（1．171±0．087）明显低于对照组（1．304±0．088），P〈0．05，但比4周应激组（1．035±0．039）高，P〈0．05，而与单次应激组（1．239±0．127）相比差异无显著性，4周应激组NAA／Cr值明显低于其他3组；右侧检测显示4周应激组NAA／Cr值（1．015±0．049）明显低于其他3组（对照组，2周应激组和4周应激组分别为1．268±0．070，1．271±0．087，1．211±0．088），而其他各组间比较差异无显著性。双侧Cho／Cr值检测结果各组间均差异无显著性。应激强度与海马代谢物水平呈显著负相关，左侧和右侧的相关系数分别为-0．749和-0．804，P〈0．01。结论强迫游泳应激可以导致大鼠海马神经元生存活力的下降或结构破坏，海马区代谢物水平改变，左、右侧海马对应激的敏感性表现不对称，并以左侧海马更为明显，^1H-MRS可无创性地反映海马区代谢物水平的这一改变。

Objective To explore the mechanism of damage of hippocampus induced by stress and evalu-ate the application of Proton Magnetic Resonance Spectroscopy （^1H-MRS） in damage evaluation. Methods 24 Rats were randomly allocated into control（ n = 6 ）, single-stress（ n = 6）, 2 week-stress （ n = 6） and 4 week-stress group（ n = 6）. Forced Swimming Test（15min/d） was used to set up stress animal model. The stress effect was as-sessed by behavior test and concentration of serum corticosterone, the measurement of NAA/Cr and Cho/Cr value of both side hippocampus in vivo was accomplished by ^1H-MRS. Results Compared with control group[ （ 191.60±116.41 ） ng/ml ], single-stress group [ （359.09±67.08） ng/ml ] and 4-week stress group [ （ 287.03± 37.22 ） ng/ml], the serum corticosterone concentration of 2 week-stress group [ （1001.36±82.84 ）ng/ml] is significant higher, P 〈 0.05. The NAA/Cr value of left hippocampus of 2 week-stress group （1. 171±0. 087 ） is significant lower than that of control group（ 1. 304±0. 088 ） , P 〈 0.05, but it is significant higher than 4 week-stress group （ 1. 035±0.039） , P 〈 0.05, no difference was found between 2 week-stress （ 1. 239±0. 127 ） group and single- stress group. In the right hippocampus, the NAA/Cr value of 4 week-stress group（ 1. 015± 0.049 ） is significant lower than other three groups （ 1. 268±0. 070,1. 271±0. 087,1.211± 0. 088 respectively） , no difference was found among these three groups. There is no difference of Cho/Cr value between 4 groups in both sides. An nega- tive relationship was observed between the strengthen of stress and the relative of concentration hippocampal metab- olism, the coefficient correlation of left and right side were -0.749 and -0.804 respectively, P 〈 0. 01. Conclusions Forced swimming stress could induce decrease of vigor or cellular injury of hippocampus neurons and lead to changes of concentration of local metabolisms. Change of right and left hippocampus is asymmetric, and the left side is more severe than the right side, ^1H-MRS can reflect this change in time noninvasively.