The Activity Changes Of MMP-2,MMP-9 And TIMP-1 In Brain In Stroke-prone Renovascular Hypertensive Rats

Objective To study The activity changes of MMP-2,MMP-9 and TIMP-1 in brain tissue in stroke-prone Renovascular Hypertensive Rats. To explore the role of MMPs/ TIMPs in the development and growth hypertention cerebral hemorrhage and cerebral infarction.Methods Male Sprague-Dawley (SD) rats were operated to establish RHRSP model as described previously. The sham-operated rats were undergone the same experimental procedures except for placement of clip, they (n = 30) served as normotensive controls. Systolic BP was measured by an indirect tail-cuff sphygmomanom- eter (HX-1), in preheated (37°C, 15 minutes) conscious rats. Normal sham-operated rats (n=30) and RHRSP (n=50) were randomly elected (n=6) to remove the forebrains at 2,4,8,12,16w after oprated . Afterwards, brain sections were stained with hematoxylin-eosin (HE) for routine light microscopic observation; MMP-2,MMP-9 and TIMP-1 protein exressions were measured by immunohistochemistry.Results①The incidence rate of hypertension in the rats of hypertension group is 100%, the blood pressure keep on increasing after operation. After 2,4,8,12,16 weeks of operation, when compared with Sham-operated group at the same time, SBP is increased notablely(P<0.001);②No brain lesions were observed in the sham-opetated group at 12 weeks after renal artery constriction. The cerebrovascular lesions were found in hypertensive group at 12 weeks after renal artery constriction,mainly showed fibrinoid necrosis, hyaline degeneration, and hyper-plasia of the wall of arterioles, cell proliferation in the external layer, and stenotic lumen ;and thrombotic vascular occlusions of 4 ratswas observed in small arteries ;③A little of MMP-2, MMP-9 and TIMP-1 were expressed in brain tissue in the sham-opetated group, the amount of MMP-2, MMP-9 and TIMP- 1 were markedly increased at 4w～16w in RHRSP as compared with sham- operated rats (P <0.01).④Taken together, our results showed that there is a positive association between high blood pressure or the quantities of cerebral apoplexy in rats and the expression of MMP-2, MMP-9 and TIMP- 1 among the RHRSP(P <0.05);in addition, the contents of MMP-2, MMP-9 and TIMP- 1 correlated closely with each other(P <0.05).Conclusions Up-regulative activity of MMP-2,MMP-9 may play a role in the onset of cerebral infarcttion , cerebral hemorrhage , even mixed stroke.