抵抗素对脑慢性低灌注小鼠认知损害的改善作用

Resistin Attenuates Cerebral Chronic Hypoperfusion-caused Cognitive Impairments

目的探究抵抗素对小鼠脑慢性低灌注(CCH)相关认知损害的影响。方法3月龄C57/BL雄性小鼠随机分为双侧颈动脉狭窄(BCAS)组和假手术组(为对照)。BCAS术后30 d,BCAS组和假手术组分别随机取部分小鼠侧脑室注射抵抗素,设为BCAS+抵抗素组和假手术+抵抗素组。每组小鼠n=5。以5个时间点对小鼠进行体重监测;给予抵抗素后30 d,以旷场实验评价小鼠的运动能力和焦虑行为,新物体识别测试和Y迷宫测试评估小鼠认知功能,Westernblot法检测胼胝体髓鞘蛋白CNPase和MBP水平。结果4组小鼠的体重、运动能力和焦虑行为比较差异无统计学意义(均P>0.05),但BCAS组对新物体识别能力和空间学习记忆功能明显低于假手术组,BCAS+抵抗素组与BCAS组小鼠比较上述能力显著提高(均P<0.05)。BCAS组小鼠胼胝体髓鞘蛋白CNPase和MBP表达水平明显低于假手术组,BCAS+抵抗素组小鼠CNPase和MBP表达水平较BCAS组增加(均P<0.05)。结论脑慢性低灌注诱导小鼠认知损害,而抵抗素可显著改善其认知损害,作用机制可能与抵抗素减轻慢性低灌注造成的白质损伤有关。

Aim To investigate the efficacy of resistin on cerebral chronic hypoperfusion-related cognitive impairments.Methods Performed bilateral carotid stenosis(BCAS)surgery to establish the cerebral chronic hypoperfusion(CCH)mice model(BCAS group),with sham surgery performed as control(sham group).Thirty days after the surgery,mice from the BCAS group and the sham group were randomly selected for resistin supplementation to lateral ventricles,labeled as BCAS+resistin group and sham+resistin group.The body weights of mice were monitored at five time points.After 30 days,the mice's mobility and anxiety were examined by the open field test,and cognitive functions were evaluated by the novel object recognition and Y-maze tests.The levels of myelin proteins in the corpus callosum were detected by Western blot.Results There was no significantly difference in weight,mobility and anxiety among the four groups of mice(P>0.05).Compared to the sham group,the BCAS group's ability to recognize novel objects and the spatial learning memory function declined significantly(P<0.05).Compared to the BCAS group,the cognitive functions mentioned above were enhanced in BCAS+resistin group(P<0.05).According to the Western blot results,the levels of myelin proteins(including CNPase and MBP)in BCAS group's corpus callosum were lower than those in the sham group's(P<0.01),and compared to BCAS group,the levels of CNPase and MBP increased in the BCAS+resistin group(P<0.05).Conclusion Cerebral chronic hypoperfusion induced dysfunction in mice.Resistin supplemental therapy could significantly improve cognitive function,and the mechanism may be related to the resistin therapy in alleviating white matter damage caused by CCH.