The Research Of The Effects Hypoxic Preconditioning On NF-κB, MMP-9 Expression In Rats After Traumatic Brain

Background As a common injury type, traumatic brain injury is the research priorities of the world’s medicine (including military medicine). Moreover severe traumatic brain damage of mortality is the first place in each part of the whole body injury. By one or several moderately repetitive hypoxia, hypoxic preconditioning mobilize the body’s self-defense capability, which can reduce the severity of subsequent injury. An important inflammatory initiation factor, NF-κB(nuclear factor-κB) plays an important role in pathological changes in brain injury and its effect on neurons is one of the main aspects of which. MMP-9(matrix metalloproteinase-9) is one of the essential factors for cerebral edema caused by brain injury. The study examined after hypoxic preconditioning with traumatic brain injury caused by all groups of rats brain tissue NF-κB, MMP-9, neuronal activity, brain water content, IgG expression, and to explore hypoxic preconditioning on neurons, the degree of cerebral edema and possible mechanisms associated to NF-κB, MMP-9.Objective (1) To establish a practical and stable rat model of hypoxic preconditioning. (2) To observe NF-κB, MMP-9, neuronal activity, brain water content, IgG expression after traumatic brain injury in rats. (3) To investigate the effect of hypoxia pretreatment on changes in the indicators above, and to explore hypoxic preconditioning on traumatic brain injury and the possible mechanism.Method 216 Sprague-Dawley male rats were randomly divided into control group (Con, n=12), hypoxic preconditioning group (HPC, n=12), traumatic brain injury group (TBI,n=96) and traumatic brain injury after hypoxic preconditioning group (HPCT, n=96). According to different time after injury, TBI group and HPCT group were drawn into 1h,3h,6h,12h, 1d,3d,7d,14d subgroup (n=12). Con group directly executed. Improved Feeney method was used to make traumatic brain injury model. Drilled 5 mm diameter circular bone window in the left side midline 3 mm and closed to the coronal suture.50g weight from a height of 25cm free-fall impacted the bone window. When completed hypoxic preconditioning training (-50KPa,3h/d,3d) after Id, HPC and HPCT groups received the same blow. RT-qPCR and Western blotting were used to detect the expression of NF-κB and MMP-9, Immunohistochemistry was used to measure the average optical density of NeuN-positive and the amount of IgG leakage. The brain water content was measured by dry weight method.Result (1) In the TBI and HPC groups, the mRNA levels of NF-κB at 3h,6h,12h, 1d and the expression of NF-κB at 3h,6h,12h, 1d,3d,7d were all significantly increased(P< 0.05). The expression of NeuN in TBI and HPC groups were significantly decreased during the period from 3 h to 14 d(P< 0.05). In the HPCT group, the mRNA levels of NF-κB at 3h,6h,12h, 1d and the expression of NF-κB at 3h,6h,12h, 1d,3d,7d were lower than TBI group, however, the expression of NeuN were higher than TBI group at the same period with NF-κB expression(P< 0.05). (2) The mRNA level of MMP-9 in TBI group was markedly increased at 3h,6h,12h, 1d, 3d (P<0.05), the expression of MMP-9 and the water content of the brain tissue were significantly higher at 3h,6h,12h,1d,3d,7d. IgG expression at lh-14d all significantly increased(P< 0.05). During the period from 3h to 3d, the mRNA level of MMP-9 in HPCT was significantly lower than that in TBI group (P<0.05), and the expression of MMP-9 and the water content of the brain tissue in HPCT were significantly lower than that in TBI group at 6h,12h, Id,3d,7d. IgG expression at lh-14d were lower than TBI group(P<0.05).Conclusion (1) Our experiment of hypoxic preconditioning has good Stability and practicability. (2) Hypoxic preconditioning can protect neurons by inhibiting the expression of NF-κB within a certain time window possibly. (3) Hypoxic preconditioning could reduce the extent of cerebral edema by inhibiting the expression of MMP-9 after traumatic brain injury. This may be one of the mechanisms that hypoxic preconditioning can protect traumatic brain injury in rat cortex.