母婴分离诱导子代抑郁大鼠肠道氨基酸代谢失调

目的：探索母婴分离诱导产后子鼠的抑郁样行为及对小肠氨基酸和氨基酸转运体的影响。方法：采用母婴分离建立子鼠抑郁模型，将 SD 母鼠随机分为对照组（n=8）和母婴分离组（n=8）。对照组母鼠在产后不进行任何干预。母婴分离组的母鼠在正常分娩后与子鼠连续分离14?d，每天分离3?h。采用糖水偏好实验、新奇抑制摄食实验及强迫游泳实验评估子鼠的抑郁样行为。采用氨基酸分析仪检测子鼠小肠中氨基酸的变化，通过蛋白质印迹法检测子鼠肠道中性氨基酸转运蛋白 ASCT2、B⁰AT1和LAT1的表达。结果：与对照组比较，母婴分离组子鼠的体重在出生后第21天和28天减轻（t=4.925和 5.766，均P<0.01），糖水偏好百分比减小（t=2.709，P<0.05），摄食潜伏期延长（t=–13.431，P<0.01），强迫游泳实验中的不动时间延长（t=–3.616，P<0.01）。与对照组比较，母婴分离组子鼠小肠中的天冬氨酸浓度增加（t=–6.672，P<0.01），谷氨酰胺和甘氨酸浓度减小（t=3.107 和 9.781，均P<0.01），同时 ASCT2 和 B⁰AT1 蛋白表达减少（t=6.734和9.015，均P<0.01），而 LAT1 蛋白表达增加（t=–8.942，P<0.01）。结论：母婴分离诱导子鼠产生抑郁样行为，同时其小肠氨基酸浓度发生变化，肠道氨基酸转运体表达改变，提示肠道氨基酸功能失调与母婴分离诱导的抑郁样行为可能相关。

Disorder of intestinal amino acid pathway in depression-like offspring rats induced by maternal separation

Objective: To investigate the intestinal amino acids pathway in depression-like offspring rats induced by maternal separation. Methods: Sprague-Dawley (SD) female rats were randomly divided into a control group (n=8) and a maternal separation group (n=8). After normal delivery, the maternal rats were separated from offsprings for 14 consecutive days and 3?h per day in maternal separation group; while rats in the control group was received no interventions in postpartum. Depression-like behaviors of offspring rats were evaluated using the sucrose preference test, novelty suppressed feeding test, and forced swimming test. Amino acid analyzer was used to detect the changes of amino acid contents in the small intestine, and the expressions of alanine-serine-cysteine transporter 2 (ASCT2), solute carrier superfamily 6 member 19 (B⁰AT1) and L-type amino acid transporter 1(LAT1) were detected by Western blot. Results:The weight of the offspring rats in the maternal separation group was significantly lower than that of the control group at 21 and 28?d (t=4.925 and 5.766, all P<0.01). Compared with the control group, the percentage of sucrose preference of the offspring rats in the maternal separation group was significantly reduced (t=2.709, P<0.05), and the feeding latency was significantly prolonged (t=–13.431, P<0.01). The immobility time in FST of maternal separation group was significantly longer (t=–3.616, P<0.01).Increased concentration of aspartic acid (t=–6.672, P<0.01) and down-regulation of glutamine (t=3.107, P<0.01) and glycine (t=9.781, P<0.01) were observed in maternal separation group. Western blot analysis revealed that the protein expressions of ASCT2 (t=6.734, P<0.01) and B⁰AT1 (t=9.015, P<0.01) in maternal separation group were reduced, while the expression of LAT1 was increased (t=–8.942, P<0.01).Conclusion: Maternal separation can induce the depression-like behavior in offspring rats; the amino acid contents and the amino acid transporter expression in the small intestine are reduced, which may be related to depression-like behavior induced by maternal separation.