IMMUNOCYTOCHEMICAL STUDY OF GELATINASES AND THEIR TISSUE INHIBITORS IN BRAIN CAPILLARIES IN NORMO- AND HYPERTENSIVE RATS

Abstract

Objective - to study the distribution of MMP-2 and MMP-9 and their tissue inhibitors (TIMP-2 and TIMP-1) in the capillaries of rat brain in renovascular hypertension (RVHT). Materials and methods. The research was conducted on 35 Wistar rats with RVHT modelled by a surgical method (ligature on the left renal artery and vein). The immunohystochemical study of MMP-2, MMP-9, TIMP-2 and TIMP-1 in brain capillaries was conducted 2, 4, 6, 8, 12, 16 and 20 weeks after surgery (5 animals in each group). Level of an expression of each enzyme was estimated on the basis of concentration of the corresponding immunopositive capillaries. Then a ratio of MMP-2/TIMP-2 and MMP-9/TIMP-1 was calculated in cerebral cortex and white matter. Results. MMP-2 and TIMP-2 were found in the capillaries of the cortex and white matter, both in control animals, and during RVHT development, while MMP-9 and TIMP-1 were detected only in rats with RVHT. The number of MMP-2-positive capillaries considerably increased in the 2nd week, that of MMP-9-positive capillaries - in the 12th week of RVHT development, while the content of TIMP-2 and TIMP-1-positive capillaries was reduced to the minimal level during the specified periods, leading to significant changes of MMPs/TIMPs ratio. Conclusion. The balance between MMPs and TIMPs was disturbed during RVHT development. which is indicated by the changes of MMPs/TIMPs ratio in capillaries of the cortex and white matter. These processes may result in the destructive alterations of the blood-brain barrier, thus increasing the risk of complications in arterial hypertension.

Keywords

brain capillaries / matrix metalloproteinases / tissue inhibitors of metalloproteinases / renovascular hypertension

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