On The Effect And Mechanism Of PPAR-γ Vascular Remodeling After Carotid Artery Stent Implantation In Pigs

Objective:This dissertation is to research into the effect and mechanism of peroxisomeproliferator activated receptors-γ vascular remodeling after carotid artery stent implantationin pigsMaterial and method:12small pigs were divided into normal control group (n=4) and intervention surgerygroup(n=8), the latter group are implanted carotid artery stent to establish the animalmodel, and randomly divided into stent group (n=4) and rosiglitazone (ROSI) group (n=4).Three months after the angiography, digital subtraction angiography (DSA) technologyand HE staining are to assess vascular morphology, immunohistochemical method to detectthe expression of NF-κB and P-akt changes, Western blot method to detect vessels PPAR-γ,P-akt, akt and NF-κB changes, and scanning electron microscopy (SEM) techniques toobserve the endothelial changes.Results:1. DSA results:3months after the stent implantation for the carotid artery, the normalcontrol group remain unchanged while for the stent group it becomes significantly thinner.The developer filling is in defect, and the lumen is narrowed. For the ROSI group thedeveloper filling is good, and has no significant stenosis, compared with the normalcontrol group.2. HE staining results: The film elastic fibers of normal carotid artery are in orderlyarrangement, the internal and external elastic lamina in integrity, the endometrial inuniform, and vascular wall thickening free. Three months after the stent implantation, it canbe observed that the loose connective tissue of stent group carotid adventitial is aligned inorder, elastic membrane fiber disorganized, parts of membrane separated, the internalelastic lamina uneven, the structure of the local deformed, fractured and damaged. The stent has a loose combination with the vascular intima osteoporosis and the stent surface showsno obvious neointimal hyperplasia. For the ROSI group the loose connective tissue andelastic membrane fiber are aligned in order, the media membrane in the bottom of bracketbeam is thinner, the internal elastic lamina fibers are arranged basically intact, combiningthe stent with mild vascular intima, neointimal hyperplasia on the stent surface. Comparedwith the normal control group, the carotid artery stenosis of stent group is about(25.41±2.97)%, carotid artery stenosis in ROSI group is about (14.60±4.27)%, stent group is morestenosed than ROSI group(p<0.01).3. Immunohistochemical staining results: Three months after the stent implantation, inthe normal control group, the carotid artery blood wall of NF-κ B sees almost noexpression, but that in stent group increases significantly, up to4.63±0.52(p<0.01), and inROSI group, it is slightly elevated, about2.13±0.35(p<0.01). The expression of NF-κ Bin stent group is significantly higher than that in ROSI group (p<0.01). Similarly, threemonths after the stent implantation in the normal control group, the expression of P-akt is0.88±0.64, and that in stent group undergoes significant increase as higher as4.63±0.52(p<0.01), and it is a slight increase in ROSI group with about2.13±0.64(p<0.01). Theexpression of P-akt in stent group is obviously higher than that in ROSI group (p<0.01).4. Western blot test results:The PPAR-γ protein expression levels in stent group aresignificantly lower than those in normal control group (0.4822±0.0538vs0.1651±0.0431,p<0.01), the NF-κB and p-Akt protein expression levels increasesignificantly compared with those in normal control group (0.0470±0.0338vs0.3984±0.0474； O.2688±0.0435vs0.3297±0.0437;p<0.05);There is no significantdifference in PPAR-γ protein expression level between ROSI group and normal controlgroup (0.4310±0.0412vs0.4822±0.0538，p>0.05); compared with normal control group theNF-κB protein expression levels are slightly higher(0.0470±0.0338vs0.1909±0.0492；p<0.01). The PPAR-γ protein expression level in ROSI group increases more significantlythan that in the stent group (0.1651±0.0431vs0.4310±0.0412,p<0.01), the NF-κB andp-Akt protein expression levels decreases more significantly than those in the stent group(0.3984±0.0474vs0.1909±0.0492；0.3297±0.0437vs0.0738±0.0302；p<0.01);Akt innormal control group, stent group and ROSI group has no statistical significance(0.3238±0.0370vs0.3645±0.0422vs0.3540±0.0382；p>0.05). 5. Scanning electron microscope (SEM) results：The normal control group enjoyendothelial integrity and lumen without thickening while the stent group display obviousneointimal endothelialization of malnutrition and neointimal hyperplasia, and the ROSIgroup show complete neointimal endothelialization with no obvious neointimalhyperplasia.Conclusion:PPAR-γ could improve the vascular remodeling by regulating the expression ofPI3K/Akt and NF-κB and strengthening the vascular endothelization after stenting.