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The Influence of the Ligustrazine to MMP-9 after Procerebrum Ischemia-reperfusion of Rats

Author: LiFuShun
Tutor: YanWei
School: Jilin University
Course: Clinical
Keywords: Ischemia-reperfusion damage MMP-9 Tetramethylpyrazine
CLC: R285.5
Type: Master's thesis
Year: 2006
Downloads: 68
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Abstract

Objective:Resent years, the secondary lesion after cerebral ischemia has causedgreat attention in the inflammatory reaction, brain edema post-ischemianeurologic impairment and mutilation rate. Matrix metalloproteinase can degradeextracellular matrix, destroy basal membrane of blood vessel, and aggravate theformation of vasogenic brain edema;meanwhile, the destruction of basalmembrane can induce more inflammatory cells aggregation in the ischemic braintissue, and initiation a series of inflammatory reaction. In this experiment,through the establishment of cerebral ischemia-reperfusion model , we observedthe variation of mmp-9 and the influence of tetramethylpyrazine on mmp-9.Method: 1 Animal:75 male Wistar rats of 300-400 grams were feed withstandard feedstuff by animal experiment reseach center of Jilin University for twoweeks,140-160 g/d of each, without limitation of water. Dividing them tonon-operation group, ischemic-reperfusion group and tetramethylpyrazinetherapia group randomly. According to the differences of reperfusion time , wedivided ischemic-reperfusion group and Tetramethylpyrazine therapia group intofive subsets,6 rats per subset. Considering the change of mmp-9 with time ofnon-operation group is not conspicuous, we divided it into 2 subsets. Weprovided 33.3 mg/kg tetramethylpyrazine to both preoperatiom and postoperationin tetramethylpyrazine therapia group. 2 Modeling: cerebral ischemiamodels were established by occlusing ambi-arteria carotis communis withnon-injury bulldog clamp for 30 minutes, and detected the change of reperfusionmodels at different phase (6-hour,24-hour,48-hour,72-hour and 5-day). 3. Toget samples: we executed the rats and took brain samples at different phase,removed antinion and took frontal lobe on the ice sheets. 4.Gelatinase-zymography were used to detect the content of mmp-9 in differentsamples. Result:there was small amounts of expression of mmp-9 inprocerebrum at different phases in non-operation group;in theischemic-reperfusion group, we could observe the expression of mmp-9 in the6-hour subset, and conspicuous expression of mmp-9 in the 24-hour subset and48-hour subset in the brain tissue of rats. There was expression of mmp-9 in braintissue in the subsets of 3-day and 5-day subsets in the ischemic-reperfusion group,but it was lower than the 24-hour and 48-hour subset. The content of mmp-9degraded in all subsets in tetramethylpyrazine therapia group than thecorresponding phase of ischemic-reperfusion group except thetetramethylpyrazine of 6-hour subset, which show no statistical change .Discussion: This experiment showed that there was more conspicuous expressionof mmp-9 of 24-hour subset and 48-hour subset of ischemic-reperfusion groupthan the non-operation group statistically, which means that there wasup-regulation of mmp-9 after cerebral ischemia-reperfusion. The mechanism isstill unknown. Many scientists think that it has relationship with two factors.The first one is oxygen free radical and the second one is inflammatory reaction.The promotion zone of mmp-9 include one AP-1 and NF-Kb ,manyinflammatory factors such as TNF-α,IL-1βand LPS can act on the promotionzone and enhance translation. This experiment showed the expression of mmp-9of ischemic-reperfusion group began at the 6th hour after operation and arrivedthe apex at the 24th and 48th, after that it began to fall and lasted 3-5 days. Thisdynamic process may have relationship with physical process.The destruction of Biood-brainbarrier( BBB) play an important role in theischemic-reperfusion. After ischemic-reperfusion ,there are 3 factors ofpromotion of the BBB open. The first one is that oxygen free radical destroy thebasal membrane, the second is the degradation of active proteolytic enzyme andthe last one is dysbolism of energy. Some studies have showed that BBB openafter 4 hours of ischemic-reperfusion, and begin to close after 24 hours , after 48hours it begin to reopen more wilderly .Someone thinks the first open is causedby mmp-2 ,the second open by mmp-9, which is coincidence with the change ofmmp-9 at the 48th hour.The content of mmp-9 degraded in all subsets in tetramethylpyrazine therapiagroup than the corresponding phase of ischemic-reperfusion group except thetetramethylpyrazine 6-hour subset, which show no statistical change ,which maybe caused by the none tetramethylpyrazine treatment at that day and low thetetramethylpyrazine concentration of blood. The mechanism oftetramethylpyrazine interference is that:1. Tetramethylpyrazine is a new type of Ca2+ channel blocker,mmp-9 can exertutmost activity in the existence of Ca2+, so tetramethylpyrazine can inhibit theactivity of mmp-9 by decreasing the concentration of Ca2+.2.Tetramethylpyrazine can reduce the production of oxygen free radical whichcan induce the transcription of mmp-9, so tetramethylpyrazine can reduce theproduction of mmp-9.3.TIMP is a specific antagonist of mmp which can bind mmp-9 and inhibit theactivity of mmp-9, the binding keeps dynamic balance. Li et had found thattetramethylpyrazine can inhance the expression of TIMP, thus acting as anegative accommodation of mmp-9.Because tetramethylpyrazine has the above functions , we can say thattetramethylpyrazine can protect the BBB, the basal membrane and braim tissue.Tetramethylpyrazine can play an important role in the treatment and precautiomof ischemic cerebrovascular disease.Conclusion:1. there was up-regulation of mmp-9 after cerebral ischemia-reperfusion.2. the openning of blood brain barrier after ischemia-reperfusion was associatedwith up-regulation of mmp-9.3. Tetrametbylpyrazine may interfere the expression of mmp-9 after cerebralischemia-reperfusion.

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