高温、亚低温对大鼠重型脑损伤血脑屏障通透性的影响及其机制

Effect of hyperthermia and mild hypothermia on permeability of blood-brain barrier and its mechanism in rats with severe traumatic brain injury

目的观察高温、亚低温对重型脑损伤大鼠血脑屏障（blood-brain barrier，BBB）通透性及脑组织基质金属蛋白酶-9（MMP-9）活性和层黏连蛋白表达的影响，探讨高温、亚低温改变血脑屏障通透性的作用机制。方法72只SD大鼠随机分为假手术组、脑损伤组、脑损伤后高温组和亚低温组，检测伤灶区脑组织伊文思蓝（EB）含量、MMP-9活性和层黏连蛋白表达。结果脑损伤后高温组EB含量、MMP-9活性高于脑损伤组（P〈0．05），而层黏连蛋白含量低于脑损伤组（P〈0．05）。亚低温组EB含量、MMP-9活性低于脑损伤组（P〈0．05），而层黏连蛋白含量高于脑损伤组（P〈0．05）。结论脑损伤后MMP-9活性增高，降解层黏连蛋白，导致血脑屏障通透性增加。脑损伤后高温增加血脑屏障通透性，亚低温治疗降低血脑屏障通透性，其作用可能与二者改变MMP-9活性有关。

Objective To investigate the effect of hyperthermia and mild hypothermia on permeability of blood-brain barrier （ BBB）, activity of matrix metalloproteinase-9 （ MMP-9 ） and expression of laminin in rats with severe traumatic brain injury （TBI） so as to explore the mechanism of hyperthermia and mild hypothermia affecting permeability of BBB. Methods A total of 72 healthy adult Sprague- Dawley rats were randomly divided into four groups, ie, sham operation group （SO group）, TBI group, hyperthermia group （HT group） and mild hypothermia group （MH group）. The rats were sacrificed at 24 hours and the samples of injured brain tissues collected to detect the content of Evans blue （EB）, activity of MMP-9 and expression of laminin. Results The content of EB and activity of MMP-9 in HT group were more significantly increased compared with those in TBI group （P 〈 0.05）, while the expression of laminin in HT group was more significantly decreased than that in TBI group （P 〈 0.05 ）. However, the content of EB and activity of MMP-9 in MH group were significantly lower than those in TBI group （P 〈 0.05 ）, while the expression of laminin in MH group was significantly higher than that in TBI group （ P 〈 0.05）. Conclusions The high activity of MMP-9 can degrade laminin and increase permeability of BBB after TBI. After TBI, hyperthermia can increase permeability of BBB while mild hypothermia does on the contrary, which may be related to their different roles in changing activity of MMP-9.