老年小鼠血脑屏障在术后认知功能障碍中的作用

The role of blood brain barrier in postoperative cognitive dysfunction of elderly mice

目的观察老年小鼠在异氟醚暴露或阑尾切除术后学习和记忆能力变化及海马区血脑屏障通透性变化情况,寻找血脑屏障改变的原因。方法 30只C57BL老年小鼠(18月龄)随机分为3组:对照组(C组)不予任何干预,手术组(S组)接受阑尾切除术,吸入组(I组)吸入异氯醚。采用伊文思蓝(Evans-blue,EB)透过率检测各组海马区血脑屏障通透性的改变,并通过Western blot检测occludin和claudin-5蛋白,观察手术后紧密连接蛋白的变化,检测MMP-2和MMP-9的改变。结果相比于吸入组及对照组,手术组的潜伏期延长,平台穿越次数减少,EB透过率增加,紧密连接蛋白occludin表达减少,MMP-2和MMP-9表达增加。结论通过增加MMP-2和MMP-9的表达,引起紧密连接蛋白occludin表达的减少,并导致血脑屏障破坏,最终引起术后认知功能障碍的发生。

Objective To observe the changes of learning and memory ability in aged mice after appendectomy or isoflurane exposure and the permeability of blood brain barrier（BBB） in hippocampus in order to find the reasons for the destruction of BBB damgge. Methods Thirty C57 BL mice（18-month）were randomly divided into 3 groups： control group（group C）,surgery group（group S） and inhalation group（group I）. The permeability of BBB in hippocampus was detected with Evans-blue（EB） quantification. The alterations of tight junction protein were measured by occludin and claudin-5 using Western blot on the same day. The changes of two matrix metalloproteinases MMP-2 and MMP-9 were detected. Results Compared with the control group and inhalation group,surgery group had longer escape latencies and less platform crossings,and EB leaked into the hippocampus. The expression of occludin decreased,while the expressions of MMP-2 and MMP-9 increased. Conclusions MMP-2 and MMP-9 may cause the decrease of the expression of tight junction occludin protein,and lead to the destruction of BBB,which resultes in postoperative cognitive dysfunction.