Cathepsin S Dog, The Influence Of Restenosis After Carotid Artery Stenting And Shu, The Study Of The Intervention

Objective: To explore whether the models of carotid atherosclerotic stenosis inBeagles can be established by the way of balloon injury and nitrogen drying ofendothelial cells in their carotid arteries with high-fat diet.Methods:19healthy beagles in male were randomly divided into2groups,group A (sham group, n=4) and group B (atherosclerotic group n=15). Carotidartery of right was only separated in group A,not injuried; group B was injuredby the way of balloonjury and nitrogen drying of endothelial cells in their carotidarteries, both of them supported by high-fat diet. Vascular ultrasound and DSAwas used to observed the carotid artery stenosis and atherosclerotic plaqueformation two months after modeling.Results: Carotid intima of group A is smooth, which show by results of thevascular ultrasound, without stenosis and plaque formation; Carotid arteries ofgroup B can be seen varying of degrees of stenosis and plaque formation. DSAresults show group B is much larger than group A in stenosis rate(P <0.005).Conclusion: The model of carotid atherosclerotic stenosis in Beagles can beestablished by the way of balloon injury and nitrogen drying of endothelial cellsin their carotid arteries with high-fat diet. Objective: To observe the process of in-stent restenosis whether by Fasudil caneffect the expression of cathepsin S after Carotid artery stenting.Methods:12healthy beagles in male were randomly divided into3groups,group A (sham operation group, n=4as previous sham operation,) and groupB (group of bare stent n=4previous beagles with modeling of the carotidartery atherosclerosis) and group C (group of bare metal stent+fasudil n=4previous beagles with modeling of the carotid artery atherosclerosis).8baremetal stents were placed in the common carotid artery stenosis of group B andgroup C. Fasudil was given to group C two hours after intervention (intravenousinfusion,3mg/kg/time,2times/day,seven days totally). DSA and vascularultrasound were examined to observe the situation of the group A to select theright common carotid artery, group B and group C option within the stentedsegment： HE and elastic fiber staining observed pathomorphological situation;mRNA of Cat S expression was measured by RT-PCR; expression of PCNA,a-SMA were detected by immunohistochemical staining. P <0.05was consideredsignificant statistically differences by SPSS17.0for analysis of One-wayANOVA. Results:1. Vascular ultrasound showed no thrombosis in the lumens two months laterafter stenting. DSA results showed the lumens of group A were smooth withoutstenosis; whose differences has statistically significances(P <0.05); group B ishigher than group C in stenosis rate(P <0.05).2. HE and elastic fiber staining showed no intima hyperplasia in group A, butwas significant in group B and C; the neointimal thickness, area and stenosis ratein group B were higher than group C (<0.05).3. The expression of Cat S mRNA by RT-PCR suggested Cat S mRNA appearedlow expression in group A, but increased in group B and C, the differences hasstatistically significances(P<0.05). And the level of expression in group B ishigher than group C (P <0.05).4. Immunohistochemical staining of a-SMA showed a large number of a-SMAexpressed in media of all three groups. Group A appeared on expression ofa-SMA-positive outside of the elastic intima, but opposite in the new intima ofgroups B and C; the mean optical density value of a-SMA in group B is higherthan in group C(P <0.05).5.Immunohistochemical staining of PCNA implied positive in extima of group A,less expressed in media, and positive more around the stents and in neointimal ofgroup B and C; The value of average optical density in neointimal of group Bwas higher than C (P <0.05).6.Person correlation coefficient analysis showed: Cat S mRNA and a-SMA andPCNA optical density and Intima-media thickness was positively correlated. r values were: Cat S mRNA VS PCNA, a-SMA， Intima-media thickness r=0.834,0.901,0.815PCNA VS a-SMA,Intima-media thickness r=0.886,0.657.Conclusion:1. Expression of Cat S was increased significantly after Carotid artery stenting inbeagles, suggested that Cat S participated the process of in-stent restenosis.2. Fasudil may inhibit the process of in-stent restenosis by reducing theexpression of Cat S after Carotid artery stenting, whose mechanism may berelevant of inhibition of Cat S, which could cause smooth muscle cells migrationand proliferation.