| Objectives:To study the potential relationship between rennin-angiotensin system(RAS) and Connexins (Cx) in the process of restenosis in order to discuss the possible mechanism of restenosis, we established double-balloon injury rabbit iliac artery model and observed the pathological changes, expression of Cx43and local levels of Angll in restenotic lesions.Moreover, telmisartan was given to explore its effect on the expression of Cx43, and its possible role in the prevention of restenosis.Methods:Thirty New Zealand White rabbits were randomly divedied into3groups:control group(n=10),restenosis model group(n=10) and telmisartan group(n=10). Restenosis model group and telmisartan group followed high-fat diet after the first balloon injury of iliac artery to establish atherosclerosis model.4weeks later, these two groups received the second balloon angioplasty performed at the iliac artery lesions.Then the two groups fed high-fat diet for another four weeks. The telmisartan group was also given telmisartan(5mg/kg·d) after operation.After4weeks, all rabbits were killed and20ml blood sampling were obtained to test the levels of CHO,TG and AngⅡ before sacrifice. Iliac arteries were then cut down for HE staining, immunohistochemiscal analysis, testing the local levels of AngⅡ and detecting the expression of Cx43mRNA as well.Results:1.Serum index:As compared with the controls, restenosis model group and telmisartan group exhibited higer serum levels of CHO and TG (P<0.05). However, the difference of serum lipid levels between the two groups was not significant(P>0.05).2.Histopathologic analysis:The vessels of control rabbits were pink, thin and soft. HE stainining indicated that the intima consisted of endothelial cells and intimal elastic lamina and VSMCs in the medium arranged regularly. However,the vascular wall of restenosis lesions was hard, white and thick,which accompanied with norrow lumen.HE staining also showed neointimal hyperplasia with VSMCs proliferation and internal elastic lamina fracture.Additionally,in the medium VSMCs proliferated,arranged disorderly,and migrated to intima.In telmisartan group, the vessels showed softer vascular wall and larger lumen when compared with those of restenosis group. Furthermore, in this group HE staining indicated thickened vascular wall with intact internal elastic lamina. By using immunohistochemistry to detect a-smooth muscle actin(a-SMA),we confirmed that the proliferated cells in neointima were VSMCs in restenosis model group and telmisartan group.Computer-assisted histomorphometric analysis showed the intima thickness of both restenosis model group (266.1179±70.2696) μm and telmisartan group (68.2233±24.3754)μm increased compared with that of control group (2.8457±0.1860) μm(P<0.01).In addition, telmisartan group exhibited thinner intima when compared with restenosis group(P<0.01). Immuohistochemical analysis indicated Cx43expressed in all iliac arteries of three groups.As compared with controls, more Cx43expression was detecd in neointima and media in restenosis model group and telmisartan group.And the Cx43expression of telmisartan group was lower than that of restenosis model groups.3.AngⅡ assay:The local levels of AngⅡ were enhanced(P<0.05,P<0.01,respectively) in restenosis model group and telmisartan group when compared with those of controls.However,there was no difference between the two groups. Additonally, the plasma levels of Ang II were not significantly different among three group4.RT-PCR:Comparing with control group and telmisartan group,the expression of Cx43mRNA increased in restenosis model group (P<0.01,respectively). Telmisartan group showed more Cx43mRNA expression than that of control group.but the difference was not statistically significant.Conclision:1. This research successfully eatablished restenosis model through high-fat diet and double-balloon injury in rabbit iliac artery.2. The possible mechanism of our restenosis model:Activated local RAS induced by balloon injury upregulated Cx43expression through AT1R,which led to enhancement of the exchange of information, materials and energy among cells.The increased cellular communication could stimulate the migration and proliferation of VSMCs,which would promote neointimal hyperplasia.Finally, restenosis occured.3. In our study, Telmisartan, a specific AT1R blocker, might inhibit the migration and proliferation of VSMCs, which led to neointimal hyperplasia. by down-regulating the express of Cx43in vescular wall.So we supposed that Telmisartan might play a certain role in the prevention of restenosis after PCI. |
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