p38 MAPK抑制剂SB202190对血管性痴呆大鼠海马中多种氨基酸含量的影响

Effects of p38 MAPK inhibitor SB202190 on contents of several kinds of amino acids in hippocampus of rats with vascular dementia

目的探讨p38 MAPK抑制剂SB202190对血管性痴呆(VD)大鼠海马中谷氨酸(Glu)、谷氨酰胺(Gln)、牛磺氨酸(Tau)、甘氨酸(Gly)以及γ-氨基丁酸(GABA)含量的影响。方法 24只清洁级健康雄性3个月龄SD大鼠随机分为假手术组、VD模型组和抑制剂组,各8只。VD模型组采用永久性结扎双侧颈总动脉法建立VD大鼠模型,假手术组剥离双侧颈总动脉但不结扎,抑制剂组为大鼠建立VD模型后给予侧脑室注射p38 MAPK抑制剂SB202190。应用Morris水迷宫检测建模大鼠学习记忆功能,采用微量透析法采集大鼠海马DG区样本并检测其多种氨基酸含量。结果假手术组和抑制剂组一般行为学和水迷宫检测学习记忆功能明显优于VD模型组大鼠,其平台潜伏期时间短于VD模型组,停留平台象限时间和穿越原平台次数均显著高于VD模型组(均P<0.05)。与假手术组相比,VD组和抑制剂组Glu、Gln及Tau含量明显下降,Gly和GABA含量明显升高;与VD模型组比较,抑制剂组Glu、Gln及Tau含量明显升高,Gly和GABA含量明显下降(均P<0.05)。结论 p38 MAPK抑制剂对VD海马功能损伤具有保护作用,可能与其能够有效调节VD导致的氨基酸代谢异常,调控多种氨基酸的分泌功能有关。

Objective To investigate the effects of p38 MAPK inhibitor on glutamate (Glu), glutamine (Gln), taurine amino acid (Tau), glycine (Gly) and gamma aminobutyric acid (GABA) in hippocampus of rats with vascular dementia (VD).Methods Twenty-four healthy male SD rats were randomly divided into sham operation group, VD model group and inhibitor group. VD model was established by permanent ligation of bilateral carotid artery method, and the sham operationgroup stripping bilateral carotid artery but not ligation. Rats of the inhibitor group were injected p38 MAPK inhibitor SB202190 after the establishment of VD model. Morris water maze was used to evaluate the learning and memory function of rats. The samples of DG region of hippocampus were collected by microdialysis, and the contents of amino acids were detected. Results The learning and memory abilities were significantly better in sham operation group and p38 MAPK inhibitor group than those of VD model group. The latency time was significantly shorter in p38 MAPK group than that of VD model group. The time of locating the platform quadrant and the number of crossing the original platform were significantly higher in sham operation group and p38 MAPK inhibitor group than those of VD model group (P <0.05). Compared with sham group, the levels of Glu, Gln and Tau were significantly lower, and Gly and GABA were significantly higher, in VD group and p38 MAPK inhibitor group (P <0.05). Compared with VD group, Glu, Gln and Tau were significantly increased,Gly and GABA were significantly decreased in p38 MAPK inhibitor group (P <0.05). Conclusion p38 MAPK inhibitor has protective effect on VD hippocampal injury, which may be related to its ability to inhibit VD-induced abnormal secretion of amino acids and regulate the secretion of various amino acids