| 陈彬彬,万海方.新生期母婴分离对小鼠不同年龄段内脏痛敏及焦虑抑郁行为的影响[J].浙江中西医结合杂志,2021,31(8): |
| 新生期母婴分离对小鼠不同年龄段内脏痛敏及焦虑抑郁行为的影响 |
| Effects on visceral hypersensitivity of different ages and anxiety-depression behavior in mice induced by neonatal maternal separation |
| 投稿时间：2021-02-03 修订日期：2021-07-07 |
| DOI： |
| 中文关键词: 母婴分离 内脏痛觉高敏 焦虑样行为 抑郁样行为 |
| 英文关键词:maternal separation visceral hypersensitivity anxiety-like behavior depressive-like behavior |
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| 中文摘要: |
| 摘要：目的 探讨新生期母婴分离对小鼠不同年龄段内脏痛敏及焦虑抑郁行为的影响。方法 将新生期小鼠随机分为母婴分离（MS）组和非母婴分离（NMS）组，MS组小鼠于出生后第2 ~ 15天每天与母鼠分离3 h，NMS组小鼠不予处理；待小鼠成年后，按年龄分为青年组（3月龄）、中年组（10月龄）和老年组（18月龄），分别进行腹外斜肌放电实验和内脏痛阈检测实验，观察小鼠内脏痛敏变化。实验进一步将NMS组和MS组小鼠分别给予急性束缚应激2 h，分为NMS组、急性束缚应激组（NMS+R）、MS组和母婴分离+急性束缚应激组（MS+R），分别进行高架十字迷宫和旷场实验，观察小鼠焦虑样行为改变；NMS组和MS组小鼠进行糖水偏好实验，观察小鼠抑郁样行为改变。结果 在20mmHg结直肠扩张（CRD）压力刺激下，与NMS组相比，MS组小鼠腹外斜肌放电波幅在青年组和中年组中显著升高[青年组（22.04±3.24）μv比（14.70±3.10）μv，中年组（19.22±4.60）μv比（13.79±4.24）μv，P < 0.05或P < 0.01]；在40mmHg CRD压力刺激下，与NMS组相比，MS组小鼠腹外斜肌放电波幅在青年组和中年组中显著升高[青年组（35.56±3.32）μv比（24.11±3.29）μv，中年组（32.38±4.43）μv比（25.61±3.67）μv，P< 0.01]；在60mmHg CRD压力刺激下，与NMS组相比，MS组小鼠腹外斜肌放电波幅在青年组中显著升高[（47.16±4.24）μv比（36.96±4.63）μv，P < 0.01]；与NMS组相比，MS组小鼠内脏痛阈阈值在青年组和中年组中显著降低[青年组（57.78±7.84）mmHg比（70.25±9.21）mmHg，中年组（59.79±9.07）mmHg比（70.00±6.32）mmHg，P< 0.05]，表现出内脏痛觉高敏，随着小鼠年龄增加，内脏痛敏症状可缓解。在高架十字迷宫和旷场实验中，与NMS组相比，MS组小鼠在开臂次数百分比、开臂滞留时间百分比、中心区域停留时间和旷场总距离均显著减少[开臂次数百分比（34.84±5.78）%比（48.26±7.61）%，开臂滞留时间百分比（20.72±4.66）%比（31.39±4.80）%，中心区域停留时间（25.50±8.15）s比（38.81±5.07）s，旷场总距离（21.77±2.41）m比（30.42±5.41）m，P< 0.01]，表现出显著的焦虑样行为改变；给予急性束缚应激后，与NMS+R组相比，MS+R组小鼠在开臂次数百分比、开臂滞留时间百分比、中心区域停留时间和旷场总距离均显著减少[开臂次数百分比（29.39±2.57）%比（38.65±5.04）%，开臂滞留时间百分比（15.53±4.80）%比（24.45±5.65）%，中心区域停留时间（20.33±4.98）s比（30.04±7.88）s，旷场总距离（18.57±1.68）m比（25.18±2.72）m，P< 0.05或P< 0.01]，可进一步加重小鼠焦虑样行为；糖水偏好实验中，与NMS组相比，MS组小鼠糖水消耗百分比降低[（37.91±13.44）%比（55.64±21.41）%，P< 0.05]，表现出显著的抑郁样行为。结论 新生期母婴分离能够引起小鼠成年后内脏痛觉高敏和焦虑抑郁样行为改变，内脏痛敏症状可随小鼠年龄增加而逐渐缓解，而对急性束缚应激的焦虑调节能力显著降低。 |
| 英文摘要: |
| Abstract: Objective To explore the effects on visceral hypersensitivity of different ages and anxiety-depression behavior in mice induced by neonatal maternal separation. Methods The neonatal mice were randomly divided into maternal separation group (MS) and non-maternal separation group (NMS), and MS group were separated from the mother mice for 3 h per day from days 2 to 15 after birth, while NMS group mice were not treated; When mice were adult, they were divided into youth group (3 months old), middle age group (10 months old) and old age group (18 months old) by age, and abdominal external oblique muscle electromyography test and visceral pain threshold test were performed to observe the changes of visceral pain sensitivity in mice. Further the mice of NMS group and MS group were given acute restraint stress for 2 h, and then divided into NMS group, acute restraint stress group (NMS + R), MS group and MS+R group, to observe the changes of anxiety-like behavior in mice by the elevated plus maze test and the open field test; Sugar preference test was performed to observe the changes of depression-like behavior in mice of NMS group and MS group. Results Compared with NMS group, the amplitude of external oblique muscle discharge of MS group was obviously increased in youth group and middle age group under 20mmHg colorectal dilatation (CRD) pressure stimulation [youth group (22.04±3.24)μv vs (14.70±3.10)μv, middle age group (19.22±4.60)μv vs (13.79±4.24)μv, P < 0.05 or P < 0.01]; Compared with NMS group, the amplitude of external oblique muscle discharge of MS group was obviously increased in youth group and middle age group under 40mmHg CRD pressure stimulation [youth group (35.56±3.32)μv vs (24.11±3.29)μv, middle age group (32.38±4.43)μv vs (25.61±3.67)μv, P < 0.01]; Compared with NMS group, the amplitude of external oblique muscle discharge of MS group was obviously increased in youth group under 60mmHg CRD pressure stimulation [(47.16±4.24)μv vs (36.96±4.63)μv, P < 0.01]; Compared with NMS group, the threshold of visceral pain of MS group was obviously reduced in youth group and middle age group [youth group (57.78±7.84)mmHg vs (70.25±9.21)mmHg, middle age group (59.79±9.07)mmHg vs (70.00±6.32)mmHg, P < 0.05] which showed visceral hypersensitivity; With the increase of age, visceral hypersensitivity can be significantly alleviated in MS group mice. Compared with NMS group, the percentage of open arms entries, percentage of open arms time, time in central region and total distance in open field of MS group were obviously reduced in both elevated plus maze test and open field test [percentage of open arms entries (34.84±5.78)% vs (48.26±7.61)%, percentage of open arms time (20.72±4.66)% vs (31.39±4.80)%, time in central region (25.50±8.15)s vs (38.81±5.07)s, total distance in open field (21.77±2.41)m vs (30.42±5.41)m, P < 0.01] which showed significant anxiety-like behavior; Compared with NMS+R group, the percentage of open arms entries, percentage of open arms time, time in central region and total distance in open field of MS+R group were obviously reduced after acute restraint stress [percentage of open arms entries (29.39±2.57)% vs (38.65±5.04)%, percentage of open arms time (15.53±4.80)% vs (24.45±5.65)%, time in central region (20.33±4.98)s vs (30.04±7.88)s, total distance in open field (18.57±1.68)m vs (25.18±2.72)m, P < 0.05 or P < 0.01] which can aggravate anxiety-like behavior in mice; Compared with NMS group, percentage of sugar preference of MS group was obviously reduced [(37.91±13.44)% vs (55.64±21.41)%, P < 0.05] which showed obvious depression-like behavior in sugar preference test. Conclusions Neonatal maternal separation can cause visceral hyperalgesia which can gradually disappear with the increase of age in mice after adulthood, and that can also cause anxiety and depression-like behavior, while the anxiety regulation ability of acute restraint stress in mice was decrease significantly. |
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