雷帕霉素孕期干预对子代自闭症模型大鼠认知功能的影响

目的：观察雷帕霉素孕期干预对子代自闭症模型大鼠认知功能的影响。方法：取14只孕鼠随机分为正常组（n=3）、模型组（n=4）、雷帕霉素（RAPA）对照组（n=3）和干预组（n=4），其中模型组和干预组孕12.5 d大鼠用丙戊酸钠（VPA）600 mg/kg一次性腹腔注射制备子代自闭症模型，RAPA对照组和干预组从孕13 d开始每天给孕鼠灌胃RAPA 4 mg/kg直至子代大鼠23 d断奶，正常组和模型组孕鼠给予溶剂麻油对照。在上述4组孕鼠生产后取全部子代雄性幼鼠分别为15，27，21和26只，进行行为学检测鉴定模型，并进一步检测子代大鼠的机械刺激缩足反应阈值（PWMT）、不同光强度下的甩尾反射潜伏期（TFL）和学习记忆功能。结果：模型组大鼠的生长发育指标和探究行为能力均低于正常组，且较正常组大鼠有强烈的重复刻板行为（P<0.05），而干预组与模型组的各项检测指标相比均呈逆转（P<0.05）；模型组大鼠的PWMT较正常组升高（P<0.01），干预组大鼠的PWMT较模型组降低（P<0.01）；4组大鼠的TFL均呈现随光刺激强度增强而缩短的时反应量-效关系（TDRR，P<0.01），其中模型组大鼠的TDRR曲线较正常组右移（P<0.01），干预组较模型组左移（P<0.01），并在光强度34、51、76时模型组的TFL较正常组延长（P<0.01），干预组较模型组缩短（P<0.01）；Morris水迷宫实验的空间探索检测中，模型组的大鼠穿越原平台位置的次数较正常组减少（P<0.01），干预组较模型组增加（P<0.05）。 结论：雷帕霉素孕期干预对子代自闭症模型大鼠的行为障碍、痛觉耐受及记忆能力都有一定程度的缓解作用。

Effects of rapamycin intervention during pregnancy on cognitive function of autism model in rat offspring

AIM: To observe the effects of rapamycin pregnancy intervention on cognitive function of autism model in rat offspring. METHODS: Fourteen pregnant rats were randomly divided into normal group (n=3), model group (n=4), rapamycin (RAPA) control group (n=3) and intervention group (n=4). The model group and intervention group were i.p. injected with sodium valproate 600 mg/kg at embryonic day (E) 12.5 to establish autism model in rat offspring. RAPA control group and intervention group were i.g. given RAPA 4 mg/kg every day from the 13th day of gestation until the offspring rats were weaned at 23 days. After the birth of the above four groups of pregnant rats, 15, 27, 21 and 26 offspring male rats were selected to conduct behavioral tests to identify the model. Then, paw withdrawal mechanical threshold (PWMT), tail flick latency (TFL) evoked under different light intensity and learning and memory function of offspring rats were further detected. RESULTS: Rat offspring in the model group had lower growth and development indexes and exploratory behavior ability, but stronger repetitive stereotyped behavior compared with the normal group (P<0.05), while the indexes between the intervention group and model group were reversed (P<0.05). The model group had higher PWMT than normal group (P<0.01) and the PWMT of intervention group was lower than that of model group (P<0.01). The TFLs of rats in 4 groups showed a timed dose-response relationship (TDRR, P<0.01), that is, TFLs were shortened with the increase of light intensity. The TDRR curve of model group shifted to right compared with normal group (P<0.01) and intervention group shifted to left compared with model group (P<0.01). At the light intensity of Focus 34, 51 and 76, the TFLs of model group were longer than those of normal group (P<0.01) and intervention group had shorter TFLs compared with model group (P<0.01). In spatial probing trial of Morris water maze test, the platform crossover number in model group was less than that in normal group (P<0.01) and that in intervention group was more than model group (P<0.05). CONCLUSION: RAPA intervention during pregnancy may alleviate behavior disorder, pain tolerance and memory function of autism model in rat offspring to some extent.