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Time Course Of Early Restenosis Of Rabbit CASS Model After CEA And The Inhibitory Effects Of Rhadiola Compound On It

Posted on:2004-03-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:H Y TongFull Text:PDF
GTID:1104360092486337Subject:Neurosurgery
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BACKGROUND: With the increasing generalization of CEA, restenosis is attracting more attentioa After all, most of the researches were limited in the field of restenosis after angioplasty for coronary artery diseases, few study involves CEA. Studies of animal models are mainly based on histological methods, which lack of observation of serial changes of the same artery. Although several agents are somewhat successful in animal experiments to prevent restenosis, but the clinical results are far from satisfactory. Based on the special advances, Chinese medicine and Chinese herbs may make some breakthrough in this field and this kind of research is one of the focuses of both foreign and Chinese researchers. The rhadiola compound can promote blood circulation and mitigate thrombosis, enhance common body condition, inhibit aggregation of platelets, improve blood flow, salidroside in rhadiola inhibits rabbit smooth muscle cell proliferation simulated by hypoxia, inhibits DNA synthesis, decreases cells of G2/M phase, decreases the expression of c-fos, c-myc oncogenes. There is still no research involves the effects of rhadiola compound on restenosis.PURPOSE: 1 .To explore the main mechanism and the time course of early restenosis after CEA. 2. To serially observe the rabbit carotid CASS model as well as title changes after CEA with the application of high resolution color Doppler ultrasound and high resolution MRI. 3.To observe if compound capsule of rhadiola could inhibit restenosis after CEA and preliminarily study the mechanisms.METHODS: Using New Zealand Rabbits, lesions are created by air-drying an isolated segment of common carotid artery(120ml/min × 15min) and feeding the rabbits a diet of 2% cholesterol, 6% peanut oil for 2 months. High-resolution color Doppler ultrasound examinations are taken before CEA, early after CEA and before killing of the rabbits. High-resolution MRI examinations are taken before CEA for 4, 10 days after CEA for 2 rabbits, and try to compare the results with histological examination. Histological samplesare collected at 1,5,10,20,30,40,60 days after CEA respectively. Agents are gastric gavaged from 7 days before CEA to the sampling day(140mg/day/rabbit). Slide samples are stained with HE, VG, and PCNA, α-SMA, PDGF-A, TGFβ, CD3, CD68 immuno-histologic-chemistry stain. Three vessels of both rhadiola and non-rhadiola rabbits are observed with electron microscope. Quantitative analysis is made by software in computer.RESULTS: 1. Four grades of ultrasound examination correspond different degrees of rabbit CASS lesions, grade 1: normal artery wall; grade 2.5: consistent fatty streak and early fibrosis; gradeS: fatty accumulation and fibrosis of vessel wall; grade 4: well defined fibrous lesions protrude to the lumen. MRI reveals the outline, shape and some component of the CASS lesion, well compared with the histological samples of both the lumen and the lesion, as well as the outline of neointimal 10days after CEA. 2. Early thrombosis is found Iday after CEA, acute inflammation occurs in 5 days after CEA. Neointima forms at 10 days after CEA, area of the plaques increases continually in 30 days after CEA, more than >95% cells are smooth muscle cells, the area of plaque increases more but becomes stable at 40 days after CEA, the media changes into intima and becomes hard to tell 60 days after CEA. The remaining areas of lumen change irregularly, with the smallest at 30 days after CEA, similar changes occur in the degree of stenosis. 3. Thickness of plaques, area of plaques, common area of vessels, remaining areas of vessels and degree of stenosis are quite significantly different between rhadiola and non-rhadiola rabbits, P=0.0001. PCNA and PDGF-A are significantly different between rhadiola and non-rhadiola rabbits. TGF 3 in rhadiola rabbits is significantly lower than in non-rhadiola rabbits at 10 and 20 days after CEA, PO.05. Under electron microscope, the activity of SMC is significantly different between rhadiola and non-rhadiola rabbits at 20,30 days after CEA.
Keywords/Search Tags:Restenosis
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