Effects Of PTX On Expression Of MMP-1 And TIMP-1 After Injury Of Blood Balloon

Background and Objective: Percutaneous transluminal coronary angioplasty and stent implantation are an effective therapy of coronary heart diseases ,however restenosis in 30-50% of PTA patients become the exigent problem in clinic. The pathogenesis of the restenosis concludes thrombus formation and neointimal hyperplasis in the early time and the artery remodeling later. In this procss,restrictive remodeling is consider the key factor. The matrix metalloproteinases(MMPs) and tissue specific inhibitors of matrix metalloproteinases (TIMPs) is the major adjust factors in the balances of dissolution and aggradation in the extracellular matrix and it is also the key factor in the vascular remodling after the balloon overstrech injury in the arter .Therefore, the aim of this present study is to examine the effect of pentoxifylline(PTX) on the expression of MMP-1/TIMP-1 on the balloon overstrech injury of rabbit illiac arteries and explore the likely mechanism.Methods and Material: Forty fit adult male New Zealand rabbits were randomlydivided into tow group: (1)ballon group: received balloon injury only;(2) PTX group:intraperitoneal irrigated of PTX from 1 day before injury at a dose 42mg/kg till the animals being harvested. In each group, the animals were divided into three teams randomly The iliac arteries were analysed by cross-sectional morphometry and calculated the lumen area(LA) and total vessel area(EEL:area circumscribed by the external elastic lamina) as the measure of stenosis and constritive remodelling. The expression of MMP-1/TIMP-1 in the vessel were determined by high-SABC immunostain.we also examined the mean greym of collage within the vessel wall by Van Gieson stain to look into collage distributing and producing.Result: (1) Vessel morphometry: Both in the balloon group and PTX group, the internalexlastic lamina of the iliac arteries were ruptured after the operation and the neointima was thicken .Comparing with the balloon group ,the LA of PTX group was increased by 24% (1.02±0.21mm~2 vs. 0.82±0.15 mm~2 at week 4; P<0.05 ,与 52% (0.94±0.21mm~2 vs. 0.62±0.19mm~2 at week 12; P<0.01, respectively, the EEL were also separately magnified meanly about 21% (1.62±0.301mm~2 vs. 2.05±0.31mm~2 at week 4; P>0.05) 及 54%( 1.22±0.34mm2 vs. 1.89±0.27mm2 at week 12; P<0.01, (2) MMP-imMP-1: immuno- histochemistry analysis show that expression of MMP-1 in the vessels were no significant change between the balloon group and the PTX group, there wre no statistic mean in the result. [(7.32 ± 4.79),( 7.54 ± 3.84); (5.5 ± 2.7),( 5.6 ± 3.8); (10.4 ± 4.1),( 11.5 ± 3.8)], however expression of TIMP-1 were remarkly reduce in the PTX group than control group[(16.5 ± 7.5),( 13.56 ± 7.5); (30.5 ± 7.5),( 25.3 ± 6.2); (42.5 ± 705),( 31.3 ± 6.2)]. (3) Collagen hyperplasia: The collagen fiber of balloon group was ruptured and disordered. The situation was improved by PTX. The collagen greym of adventitia in two groups was prominently different (24.36±2.68 vs. 21.40 + 3.46 at week 4; P<0.05 and 34.06 + 2.81 vs. 24.97+2.69 at week 12; P<0.01 <> The mean coolagen greym in neointima was lower than the balloon group at each time (7.31+3.50 vs. 9.86 + 3.82 atweek4; P<0.05 and 8.05±2.14vs. 11.79 + 3.12 at week 12; P<0.01oConclusion: 1 ^ After artery injury,cells in the vessel were activation, and secreted muchcollagen, collagen aggraded in the neointima and adventitia and induce the contractiveremodeling,which correlates tightly with the restenosis late on after artery injury.2> our search suggested that because PTX can adjusted the collagen decompensation,reduced the accumulation of collagen ,thart PTX was likely to pretect the artery fromrestenosis after balloon injury.3 ^ PTX can restrain the artery contractive remodeling after balloon injury and pretect theartery from restenosis. This effect maybe come from inhibition of expression of TIMP-1 andthe revertion of balance of MMP-1 /TIMP-1.