创伤性脑损伤大鼠脑组织基质金属蛋白酶的表达

目的研究创伤性脑损伤大鼠脑组织基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)和基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达规律及其参与创伤性脑水肿形成的作用机制。方法选择SD大鼠115只,随机分为假手术组(23只)和创伤组(92只),创伤组又分为6h,1、3和5天4个时间点,每个时间点的大鼠23只,建立大鼠创伤性脑损伤模型,采用免疫组织化学方法检测脑组织MMP-2和MMP-9的表达;并观察脑组织含水量、血脑屏障通透性、脑微血管分布密度及超微结构等变化。结果创伤组6h创伤灶周围脑组织中即开始出现MMP-2和MMP-9的表达,MMP-9表达水平在1天达高峰,MMP-2的表达则在5天达到较高水平,与假手术组比较,差异有显著性意义(P<0.01)。MMP-9表达与脑组织伊文思蓝含量的变化呈正相关;MMP-2在创伤后1、3和5天的表达与创伤灶周围微血管面积密度变化一致。结论MMP-2和MMP-9参与了创伤性脑损伤后血脑屏障破坏、脑水肿形成、炎性反应等过程,并在损伤修复中可能有重要作用。

Expression of matrix metalloproteinase in brain tissue after experimental traumatic brain injury in rats

Objective To observe the changes of the expression level of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-9(MMP-9)in experimentally injured brain tissue of rats and the mechanism of traumatic brain edema.Methods The SD rats were randomly divided into sham operation group(n=23) and traumatic brain injury(TBI) group(n=92).The rats in TBI group were further divided into 6 h,1,3,5 day groups.The experimental TBI model was established by free falling according to Feeney's method.The expression of MMP-2 and MMP-9 protein in brain tissue of rats was investigated by immunohistochemical technique.The changes of brain water content,permeability of blood-brain barrier(BBB),cerebral microvesel distribution density and ultrastructure were also observed.Results The expression of MMP-2 and MMP-9 in the brain tissue of TBI model group appeared 6 hours after trauma and their expression reached peak on day 1 and day 5 respectively.There was positive correlation between protein expression of MMP-9 and the changes of Evan's blue content.The expression of MMP-2 was consistent with the changes of cerebral microvessel distribution density from day 1 to day 5.Conclusion MMP-2 and MMP-9 take part in the damage of BBB,the formation of brain edema and the inflammatory reaction and may play important role in the recovery of TBI.