Doxycycline Mudulates Matrix Metalloproteinase Activity And Vascular Remodeling In Balloon-injured Rat Carotid Arteries

Objective: Based on rat common carotid balloon-injury model, we examined the inhibition ofmatrix metalloproteinase(MMP) activity by doxcycline(Doxy) and its effect on vascularsmooth muscle cell (SMC) proliferation, neointimal hyperplasia and vascular remodeling.We hope these results can elicit a novel approach to the clinical therapy of restenosis. Methods: 1,we established the rat common carotid injury model by balloon-dilatation, anddetermined the injury grade at 24h after operation and measured the neointimal thicknessat the time 14 days to evaluate if the model be successful. 2,48 SD rats were divided randomly into control group and Doxy treatment groupwhich were administered Doxy at a dose of 30mg/kg/d. We measured the acitivity ofMMPs by gelatin zymography in the tissue of injured carotid arteries at different time afteroperation. 3 , Carotid artery samples of control and Doxy treatment groups underwenthistological and morphometric analyses at 1,3,7,14,28 days after injury respectivly, and wemeasured the thickness and area of neointimal, lumen area and the proliferation of SMCsusing a computer-assisted morphometric analyses system. Results: 1,There were significant differences in injury grade between control and treatmentgroup, and evident thick neointimals appeared at 14 days after injury. 2,After Doxy treatment, the activity of MMP-9 in the carotid arteries was reduced to65.5% of control levels at 3 days after balloon injury(P<0.01), and the activity of MMP-2wes reduced 40.0% at 7 days after injury(P<0.01). 2第二军医大学硕士论文 摘要 3,The thickness and area of neointimal was siginificantly decreased at 14,28 daysafter injury in the Doxy-treated rats compared to controls(P<0.01); The lumen area wasincreased by 90.4 % in treated groups at 28 days after injury compared with controls(P<0.01), and Doxy treatment significantly reduced intimal SMC proliferation from62.76±1.02 % in controls to 43.23±1.06% at 7 days after injury(P<0.01). Conclusions: We established the rat common carotid injury model successfully byballoon-dilatation. Doxy treatment inhibits the activity of MMPs, the SMC proliferation ofintimal, neointimal hyperplasia and vascular remodeling which suggesting Doxy treatmentbe useful in preventing restenosis after PTCA.