| Objective:Establish the models of Rabbit Aortic atherosclerosis DES Implantation,to observ the effect of Huatan Huoxue Jiedu prescription on atherosclerotic plaques in the stented neoatherosclerosis,and to study the possible mechanisms through the MAPKs signaling pathway in the formation of atherosclerotic plaque in the stenting neo atherosclerosis.Methods:1.Establishment of drug-eluting stent implantation model and experimental grouping of atherosclerotic stenosis in abdominal abdominal aorta of rabbits: 40 male adult Japanese white rabbits(clean grade)were selected to receive preconditioning for 1W to perform abdominal aortic balloon injury.The fat feed(basal diet with cholesterol 5%,lard 5%,and egg yolk powder 3%)was fed 8W.The abdominal aorta was treated with minimally invasive DES stents and randomly divided into 4 groups: model group(MG group),Ruishu The statins group(RG group),Huatan Huoxue Jiedufang low-dose group(LG group),Huatan Huoxue Jiedu Decoction high-dose group(HG group).Among them,the composition of Huatan Huoxue Jiedu Decoction is: 15 g of Gualou Huoxue,18 g Lime White,15 g Saponaria,2g Dragon’s Blood,25 g red yeast,37 g Sanqi,25 g Lonicera,more than seven Chinese herbal medicines.Red yeast rice,Dragon’s blood,and 37 pieces are finely powdered.The melon moss,saponin,honeysuckle,and vinegar are repeatedly fried three times and then concentrated to extract.Then the above fine powder is added,vacuum-dried and crushed to obtain Chinese medicine.,administered by gavage.Each group was given an appropriate drug intervention for 24 weeks.2.The levels of serum CRP,IL-6,and MMP-9 in each group were measured by ELISA after 24 weeks of intervention with different drugs.3.OCT imaging technique was used to observe the status of stented blood vessels after stent implantation: After 24 weeks of drug intervention,the vascular lumen area,neointimal thickness,and neointimal area of each stent were evaluated.4.The expression of smooth muscle actin,smooth muscle osteopontin and macrophage CD68 were detected by immunohistochemistry.Results:1.Animal model: After the high-fat diet,the weight of the experimental rabbits increased,and the weight in the later period remained basically unchanged.Four rabbits died after balloon injury of abdominal aorta.The cause of death was considered as stress-induced injury.DES stent placement prior to abdominal aorta angiography showed a degree of vascular stenosis of about 30 to 80%.Within 3 days after surgery,a small part of the experimental rabbits showed apathy and loss of appetite,which basically improved after 3 days.The remaining experimental rabbits recovered well after surgery and had a normal diet.Rabbits in the model group died 1 immediately after DES implantation,and it was suspected that the cause of death was vascular stress delirium;2 rabbits in the low-dose group of Huatan Huoxue Jiedu Decoction died,and one DES died immediately after implantation.One died within 3 days of the operation,and one in the Huatan Huoxue Jiedu Decoction group died.The cause of death was continuous bleeding from the surgical wound.Considering that the suture is not ligated when the surgical wound is sutured,it is closely related.The rabbits in each group were in good condition until the end of the experiment.Abdominal aorta angiography in rabbits revealed that the blood vessels were clear,blood flow was normal,and stents were well adherent.The experimental rabbits had good mental state,normal shiny hair,no obvious abnormalities such as eating,two stools,and no obvious adverse drug reactions.2.Levels of serum inflammatory factors: The levels of CRP and IL-6 in serum were detected by ELISA.The results showed that compared with MG group,the expression levels of CRP and IL-6 in RG group,LG group and HG group were lower than those in MG group.Group(P<0.05);Compared with RG group,the expression of CRP and IL-6 in serum of LG group was significantly lower than that of MG group(P<0.05),and the expression of HG group had no statistical significance(P>0.05).Compared with LG group,the expression level of HG group was significantly higher(P<0.05).The expression level of MMP9 in serum showed that: compared with MG group,the expression levels of RG,LG and HG groups were significantly lower than that of MG group(P<0.05);Compared with RG group,the expression of LG was significantly lower than that of RG group.In the RG group(P<0.05),the expression in the HG group was slightly higher than that in the RG group(P>0.05).3.OCT scan: After quantitative analysis,the results showed that compared with MG group,the luminal area of RG group,LG group,and HG group was larger than that of MG group,and the lumen area of LG group was significantly larger(P<0.05).<0.05),there was no significant difference between the RG group,the HG group and the MG group(P>0.05).Compared with the RG group,there was no significant difference in the lumen area between the LG group and the HG group(P>0.05).Compared with LG group,HG group had no significant statistical significance(P> 0.05).Compared with MG group,neointimal area and neointimal thickness in RG group,LG group,and HG group were lower than those in MG group,and neointimal area in LG group was significantly lower(P<0.05);and LG group.In contrast,the neointimal area of the RG and HG groups was not statistically significant(P>0.05).4.Immunohistochemical:The quantitative analysis of a-Actin immunohisto chemistry in rabbit aorta abdominal aorta showed that: compared with MG group,the positive expression of a-Actin in RG group was slightly higher than that in RG group,but there was no statistical significance(P>0.05)The positive expression of a-Actin in LG group was significantly higher than that in RG group(P<0.05).The positive expression of a-Actin in HG group was not significantly different from that in RG group(P>0.05);a-Actin was positive in LG group.The expression of a-Actin in the HG group was slightly lower than that in the RG group,but there was no statistically significant difference between the two groups and the RG group.The HG group was statistically significant compared with the LG group(P< 0.05).The immunohistochemical quantitative analysis of vascular OPN and CD68 in abdominal aorta of rabbits in each group showed that the positive expressions of OPN and CD68 in RG group,LG group and HG group were significantly lower than those in MG group,with significant statistical significance(P <0.05);The positive expressions of OPN and CD68 in LG and HG groups were not statistically significant compared with RG group(P>0.05).The positive expression of OPN and CD68 in RG group and HG group had no significant difference(P>0.05).Conclusions:1.Huatan Huoxue Jiedu Fang can reduce the expression of serum inflammatory cytokines CRP,IL-6 and MMP9 after DES implantation,and it can inhibit the inflammatory reaction and inhibit the formation of new atherosclerosis in the stent.2.Huatan Huoxue Jiedu Fang can inhibit the phenotypic transformation of VSMC,inhibit the intimal proliferation and migration;inhibit the overexpression of macrophage CD68,and have anti-aortic atherosclerotic plaque in the stent. |
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