The Mechanism Of Effect On NF-κB And P53 By Blocking Ubiquitin-Proteasome Pathway In The Cerebral Ischemic Rats

Background and purpose The ubiquitin-proteasome pathway (UPP) represents the major pathway of intracellular non-lysosomal protein degradation and plays an important role in the regulation of inflammatory reaction. Extensive research has demonstrated that inflammatory reaction is the major pathophysiological mechanism of cerebral ischemia reperfusion injury. The NF- κ B regulates the gene transcription of many inflammatory-associated factors and therefore has been known as one of the most important regulation factors of inflammatory reaction after cerebral ischemia. So it is evident that transcriptional activity is the critical factor of determining the function of NF- κ B. The UPP leads to NF- κ B activation through degrading ubiquitinated I κ B. Using proteasome inhibitor to block UPP can inhibit its transcriptional activity and therefore regulates the inflammatory reaction which regulated by the NF- κ B. There has few research in internal on whether using proteasome inhibitor to block UPP could produce neuroprotective effect by inhibiting transcriptional activity of NF- κ B in the focal cerebral ischemia rats. So, we assumed that by inhibiting transcriptional activity of NF- κ B through blocking UPP, inflammatory reaction could be reduced accordingly after cerebral ischemia reperfusion injury. The mechanism of neuroprotective effect produced by blocking UPP was elucidated, in order to provide theory and new method for clinical treatment of cerebral ischemia.Methods 132 healthy male Sprague-Dawley rats were randomly divided into five groups: normal group, sham operation group, normal saline control group, cerebral ischemia group and intervention group. The latter two groups rats were divided into four subgroups according to reperfusion time(6h, 12h, 24h and 7^th d). Transient focal cerebral ischemia was induced by middle cerebral artery occlusion...