miR-125b-5p在创伤性脑损伤后对脑功能恢复的作用机制研究

Study on the mechanism of miR-125b-5p on brain functional recovery after traumatic brain injury

目的:探讨miR-125b-5p在创伤性脑损伤(TBI)后对脑功能恢复的作用机制。方法:运用生物信息学技术分析miR-125b-5p和MMP-15在脑外伤大鼠海马区的表达情况,建立创伤性脑损伤大鼠模型,分为假手术组(Sham组),模型组(TBI组),阴性对照组(NC组)和agomir处理组(Agomir组)。采用测量脑含水率、神经功能缺损评分(NSS)和水迷宫实验评估miR-125b-5p对脑损伤后脑功能恢复的影响,qRT-PCR检测大鼠海马体中miR-125b-5p和MMP-15表达水平。结果:生物信息学分析发现在创伤性脑损伤大鼠海马体中miR-125b-5p表达降低,MMP-15mRNA表达上调。TBI组miR-125b-5p表达量较Sham组降低(P<0.01),而Agomir组miR-125b-5p表达量较NC组上升(P<0.001)。建模后第2天TBI组脑含水率高于Sham组(P<0.01),而Agomir组脑含水率低于NC组(P<0.01)。建模后1~7天TBI组NSS评分较Sham组增加(P<0.001),而Agomir组较NC组降低(P<0.01)。水迷宫实验中TBI组大鼠平均逃脱时间长于Sham组(P<0.01),而Agomir组平均逃脱时间短于NC组(P<0.05);在脑损伤后第14天撤掉隐藏的平台,大鼠在目标区域的停留时间TBI组少于Sham组(P<0.001),Agomir组长于NC组(P<0.001)。结论:上调miR-125b-5p能缓解创伤性脑损伤大鼠神经功能缺损及认知功能障碍,可能与miR-125b-5p靶向调控MMP-15表达有关。

Objective:To investigate the mechanism of miR-125b-5p on brain function recovery after traumatic brain injury(TBI).Methods:Bioinformatic techniques were used to analyze the expression of miR-125b-5p and MMP-15 in the hippocampus of rats after traumatic brain injury.TBI rats were divided into the Sham operation group(Sham group),the model group(TBI group),the negative control group(NC group)and the agomir treatment group(Agomir group).The effects of miR-125b-5p on brain function recovery after TBI were evaluated by measuring brain water content,neurological deficit score(NSS)and water maze test,and the expression levels of miR-125b-5p and MMP-15 in hippocampus of rats were detected by qRT-PCR.Results:Bioinformatic analysis showed that miR-125b-5p expression decreased and MMP-15 mRNA expression was up-regulated in the hippocampus of TBI rats.The expression of miR-125b-5p in the TBI group was lower than that in the Sham group(P<0.01),while the expression of miR-125b-5p in the Agomir group was higher than that in the NC group(P<0.001).On day 2 after modeling,the brain water content in the TBI group was higher than that in the Sham group(P<0.01),while the brain water content in the Agomir group was lower than that in the NC group(P<0.01).On day 1-7 after modeling,NSS score in the TBI group increased compared with the Sham group(P<0.001),while NSS score in the Agomir group decreased compared with the NC group(P<0.01).In the water maze experiment,the mean escape time in the TBI group was longer than that in the Sham group(P<0.01),while the mean escape time in the Agomir group was shorter than that in the NC group(P<0.05).When the hidden platform was removed on day 14 after TBI,the stay time of rats in the target area was shorter in the TBI group than that in the Sham group(P<0.001),and the stay time was longer in the Agomir group than that in the NC group(P<0.001).Conclusion:Upregulation of miR-125b-5p can alleviate neurological deficits and cognitive dysfunction in TBI rats,which may be related to the targeted regulation of MMP-15 expression.