ABSTRACT
Matrix metallopmteinase 9(MMP-9) is one kind of matrix metalloproteinases and plays a role in the process of breast cancer metastasis. It can not only degrade the basement membrane and the extracellular matrix around tumor tissue but also promote angiogenesis, even create conditions for the growth of tumors, local invasion and distant metastasis. Current study shows that the over-expression of MMP-9 can significantly speed up the breast lymph node metastasis and the relevant research will provide guidance for clinical treatment and prognosis of breast cancer.
ABSTRACT
Objective To investigate effect of transforming growth factor β3(TGFβ3)on expression of MMP-9,MMP-2,TIMP-1 and collagen I in rats with liver fibrosis through transduction by recombinant adeno-associated virus 2(rAAV2).Methods Rats were randomly divided into 4 groups:normal control group,model group,negative control group and TGFβ3 group.Liver fibrosis model was induced by hypodermic injection of 40% CCl4.rAAV2-TGFβ3,was injected via vena caudalis of the rats one week before CCl4 Was given.All rats were sacrificed and the liver tissues were taken 8 weeks afler injection of CCl4.The histopathological changes were observed on HE sections;the expressions of MMP-9,MMP-2,TIMP-1 and collagen I were examined by histochemistry and the positive area rates were semi-quantitatively analyzed.Results Compared with the model group and negative control group,the decreases of inflammatory infiltration and collagen fibers hyperplasia were observed in the TGFβ3 group,and the expression of MMP-9 increased(q=23.664,27.746,P<0.01),the expression of collagen I(q=5.503,5.251,P<0.01)and TIMP-1(q=5.800,8.608,P<0.01)decreased,but that of MMP-2 was not changed(q=2.1 08,0.996,P>0.05).Conclusion rAAV2-TGFβ3 can reduce the histological damage and degree of liver fibrosis in rats by inhibiting expression of TIMP-1 and collagen I,and upregulating expression of MMP-9.
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Objective To explore the changes of matrix metalloproteinase-9 and blood brain barrier in cardiopulmonary resuscitation rats and effects of MMP-9 inhibitor on them.Method One hundred and twenty Sprague-Dawley(SD) rats were randomly divided into 3 groups:the sham-operated group,the resuscitation with treatment group and the resuseimfion without treatment group as control.The experiment was made in the animal experiment center of Sun Yat-sen University in Gtlangzhou.The rat eardiopulmonary resuscitation model was made by clipping trachea until asphyxia,and the restoration of spontaneous circulation(ROSC)Was defined by restoration of superventricular rhythm and mean artery pressure (MAP)≥60 mmHg for more than 5 min utes.The rats of sham-operated group were anesahetized only and endotracheal intubation WaS performed.In the resuscitation with treaUnent group ss-3cr(25,ng/ks body weight)Was given intraperitoneally after ROSC.The rats were sacrificed and samples of the brain tissue were taken inmaediately and 3 h,9 h,24 h and 48 h later.After that,the expression of MMP-9 and MMP-9 mRNA in brain tissue were detected.Water oontent and Evans blue in brain tissue Were observed.The uhmmicrostructure of brain tissue was observed under electron microscope.Analysis ofvariance wilE, done with Spssll.0 software.Results 11le expressions of MMP.9 and MMP-9m RNA ofbraintissueiUthe shanloperated group didn't show significant changees in all specimens taken at different intervals and neither the water content and tvans blue did.The Pvalue were 1.0000,0.6831,0.7124 and 0.99r75,respectively.There was no u1.tramicrostruclure change in the sham-operated group.The expressions of MMP_9 and MMP-9 mRNA in the resuscitation control group obviously increased after eardiopulmonary resuscitation,80 did the water content and Evans blue content.Compared with sham-operated group,the P value were 0.0264,0.0163,0.0000 and 0.0412,respee.tively.111e elge of ultmmicrostmeture in the resuscitation control group at different intervals were obvious.The changes of obove biomarkers in the resuscitation treatment group Was siroilar to but less in magnitude than those in the resuscitation control group.The P valHe were 0.0392,0.0373,0.O004 and 0.0180,respectively.Conclusions The expressions of MMP-9 and MMP.9 mRNA obviously increases in the cerebral ischemia model of rats with CPR,and reaches peak at 24 h.Water content and Evans blue content in brain risque obviously increases in the cerebral ischemia model of rats with CPR.BBB iS destroyed.and the peak time iS at 24 h.The injury of ultrami.crostructure of brain tissue under electron microscope iS obvious,and the peak time is at 24 h.The SB-3CT.specif-iC inhibitor of MMP-9 could decrease the expression of MMP-9 and decrease cerebral edema in the cerebral is.chemia modeJ of rats with CPR,and the protection from cerebral isehemia/reperfusion injury after CPR is obvious.
ABSTRACT
Matrix metallopmteinase(MMP),a family of proteolytic enzymes,can degradate the composition of extracellular matrix.Its structure,regulatory function and physiopathology have been deeply studied,and its role in tumor metastasis has received more attention.The tissue inhibitor of metalloproteinase(TIMP),as an endogenous MMP inhibitor,suppresses both the form and course of MMP activation.The function zone of its C-end accords with some other parts of MMP,forming an MMP-TIMP compound,to block the combination of MMP with the substrate,suppress the activation of MMP,and slow down or block the invasion and metastasis of osteosarcoma.