Correlation Between MMP-3, TIMP-3 Expression and Neuronal Apoptosis After Ischemia -Reperfusion Injury in Rates

Abstract

Matrix metalloproteinases (MMPs) play a central role in many biological processes, such as embryogenesis, normal tissue remodeling, wound healing, and angiogenesis. How MMP3, TIMP3 expression and neuronal apoptosis (Fas, Fas-L and Bcl) may provide detrimental or beneficial actions during the injury and repair processes after cerebral ischemia-reperfusion injury in rates was studied. Adult rats underwent middle cerebral artery occlusion (MCAO) by the suture method. The expression of mRNA for TIMP-3, MMP-3, and neuronal apoptosis -were estimated in samples of Brain cortices of the ischemic penumbra (IPZ) and the core ischemic zone (ICZ) from70 Rates with Ischemic control group (ICG), 10 sham-operated group (SOG) and 60 Ischemic β-sodium aescinate intervention group (IβG) using the reverse-transcriptasepolymerase chain reaction with a synthetic multicompetitor standard. Also the amounts of neuronal apoptosis positive cells were evaluated by TUNEL assay. IβG expressed significantly TIMP-3, MMP-3 mRNA more than the ICG..Also in the ischemic zone Bcl-2 mRNA was strikingly increased whereas Fas and Fas-L mRNA was considerably decreased. At same time, the amount of apoptosis cells was maximally increased at 3 hours and was lowest decreased at 72 hours after reperfusion. Altogether, these results strongly suggest that inappropriate MMP-3 expression combined with increased TIMP-3, the ratio of apoptotic cells shows positive correlation with TIMP-3 , negative correlation with MMP-3 and MMP-3, TIMP-3 Expression might modulate the process of type I and type II neuronal apoptosis through FAS pathway.