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The Effects of Minocycline on the Expression of NF-κB, ⅠκBα and TNF-α in Focal Cerebral Ischemia-Reperfusion Rats

Author: LiuYiFeng
Tutor: BaiHongYing
School: Zhengzhou University
Course: Neurology
Keywords: Minocycline Rats Cerebral ischemia and reperfusion Nuclear factor-κB Nuclear factor-κB inhibitory protein α Tumor necrosis factor α
CLC: R965
Type: Master's thesis
Year: 2011
Downloads: 93
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Abstract

Ischemic cerebrovascular disease (ischemic cerebrovascular disease, ICVD) because of its high incidence, mortality and morbidity become a killer of human health, currently only thrombolytic therapy, antiplatelet therapy and anticoagulant therapy is effective . Recanalization after thrombolytic therapy will occur reperfusion injury, cerebral ischemia-reperfusion injury is a complex pathophysiological process, inflammatory response play an important role in the process of secondary injury after brain ischemia. Nuclear transcription factor-κB (nuclear factor kappa B, NF-κB) protein is a key regulator of a variety of inflammatory mediators, which play a major physiological functions of two of the four subunits p50 and p65, both of which constitute the dimer. NF-κB inhibitory protein (inhibitor of the phosphorylation of NF-κB, IκB) degradation is the main way of the activation of NF-KB. NF-κB activation signal path to provide a potential molecular target to block the complex mechanism of inflammation and apoptosis. Minocycline (Minocycline, MC) is a semi-synthetic second-generation tetracycline derivative, easily through the blood-brain barrier to reach the central nervous system. First reported in 1998 Yrjanheikki MC neuroprotective effect in cerebral ischemia, but the mechanism is not yet completely clear. The experiment by observing application minocycline intervention on cerebral ischemia reperfusion of IκBα, NF-κB P65, TNF-α expression change and 48h brain tissue pathological changes and neuron cell apoptosis, the brain protection possible mechanisms. Materials and Methods 72 healthy adult Sprague-Dawley rats were randomly divided into sham operation group (Sham), cerebral ischemia and reperfusion model group (IR), minocycline treatment group (MT group), 24 only. 6, 12, 24 and 48 hours of observation time point after ischemia and reperfusion in each group of rats press were randomly divided into four subgroups, each subgroup 6. Reference Longa of the middle cerebral artery suture occlusion (MCAO) method appropriately modified middle cerebral artery occlusion and reperfusion model. Sham group in addition to non-plug wire, I step with the other two groups. Successful model MT group rats were given minocycline orally reperfusion first dosage 45mg/kg every 12h thereafter gavage once 22.5mg/kg, Sham group and IR group were at the same point in time given the same amount saline until killed. Hematoxylin - eosin (HE) staining ischemia reperfusion 48h brain histopathological changes; of TUNEL apoptosis in situ by detection of nerve cell the infarct cortex 48h apoptosis after ischemia-reperfusion evaluation of ischemia and reperfusion. damage to nerve cells and the neuroprotective effect of minocycline; SP immunohistochemical staining methods IKBα, NF-κB P65, TNF-α protein expression observed at each time point changes and application of minocycline prime the impact of the treatment. Results (1) after reperfusion 48h MT group histopathological changes in hippocampal CA1 region compared with the IR group significantly reduced; (2) after reperfusion 48hIR group compared with the Sham group the number of TUNEL-positive cells was significantly increased (P lt; 0.01), the MT group compared with IR group, TUNEL positive cell number was significantly reduced (P lt; 0.05); (3) of NF-κB P65 cerebral ischemia reperfusion 6h that significantly increased 24h highest expression 48h a slight decrease in the expression of; TNF- α in cerebral ischemia and reperfusion 6h that significantly elevated 24h highest expression, 48h remained high expression levels; IR group compared with the with time point Sham group hippocampal CA1 region of NF-κB P65, TNF-α-positive cells was significantly increased (P lt; 0.01); compared to the same point in time IR group, MT group hippocampal CA1 region NF-κBP65, TNF-α positive cells significantly reduced (P lt; 0.05); (4) of IκBα optical density value of IR group IκBα expression 12h minimum 24h gradual recovery; corresponding time points MT group compared to the Sham group significantly lower (P lt; 0.01), compared with the IR group was significantly higher (P lt; 0.05). Conclusion (1) cerebral ischemia-reperfusion injury IκBα reduced expression, NF-κB overactivation of expression. (2) minocycline can increase the rat cerebral ischemia reperfusion after IκBα expression, reducing the positive expression of NF-κB nuclear, reducing the positive expression of TNF-α, thereby partially blocking cerebral ischemia and reperfusion inflammatory cascade, reducing neuronal apoptosis, to play the role of cerebral protection.

The Effects of Minocycline on the Expression of NF-κB, ⅠκBα and TNF-α in Focal Cerebral Ischemia-Reperfusion Rats

Abstract

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