ABSTRACT
Objective To analyze the characteristics and significance of matrix metalloproteinase-9 (MMP-9) expression in the pathophysiological processes of tuberculous meningitis in mice.Methods Sixteen mice were intracerebroventricularly injected with H37RV suspension as the model group.Meanwhile,the other 16 mice were injected with 0.9％ sodium chloride solution as the control group.Thirty days later,all mice were decapitated and the brain tissue were respectively used to for Mycobacterium tuberculosis (M.tuberculosis) incubation,pathological changes observation,MMP-9 activity detection by zymography,blood-brain-barrier permeability and moisture content detection,and immunofluorescence stain of MMP-9,glial fibrillary acidic protein (GFAP) and integrin αM (OX-42).The t test was used to compare the differences between the two groups.Results Every experimental mouse was injected with (1.271±0.111) × 106 colony-forming units (cfu) M.tuberculosis.Thirty days later,the amount of M.tuberculosis in brain tissue homogenates was (4.900± 1.407) × 104 cfu/mL,and the hematoxylin and eosin staining showed dilatation of subarachnoid and ventricular and infiltration of a large number of inflammatory cells.The cumulative absorbance (A) of MMP-9 bands of brain tissue was 47 821 ± 19 932 in the model group and 10 082 ± 3 544 in the control group.The difference was statistically significant (t =3.728,P=0.010).The evans blue (EB) content of brain tissue was (11.8 ± 3.6) μg/g in model group and (4.7 ±3.4) μg/g in control group.The difference was statistically significant (t=2.887,P=0.028).The moisture of brain tissue was 0.849±0.035 in model group and 0.775±0.037 in control group.The difference was statistically significant (t=2.925,P=0.026).The immunofluorescence staining showed that the infected brain tissue expressed high degrees of MMP-9,GFAP and OX-42.And MMP-9 was overlapped with both GFAP and OX-42 obviously.Conclusions The activity of MMP-9 is significantly enhanced in brain tissue of mice suffering from tuberculous meningitis and participates in blood-brain barrier damage,tissue edema and inflammatory cells exudation.Microglia cells-astrocytes network is involved in the secretion of MMP-9.