| Background: The effects of carotid endarterectomy (CEA)on prevention cerebral arterial thromosis have been approved. The neointima after CEA leading to restenosis has become important factor influence on effects.To explore the formation of neointima and prevent restenosis is a hot spot in neurosurgery and vascular surgery. But the defects of traditional sutured anastomosis in vascular anastomosis is the time of vascular block too long, sutureless adhesive anastomosis are suggested overcoming that, and the new method is in stage of experiment.Objective: To observe and compare the formation of intima after CEA with sutured anastomosis and sutureless adhesive anastomosis repectively on the rabbit carotid CASS model, analyse on the level of molecul and protein about the machanism of restenosis after CEA. To investigate if the antioxidant probucol could inhibit restenosis after CEA and study the mechanisms.Methods: 1.Using New Zealand Rabbits, lesions were created by air-drying an isolated seagment of common carotid artery(120ml/min, 15min) and feeding high cholesterol diet for 2 months. At the end of time, the lesions were evaluated by color Doppler ultrasound and angiography and pathology. 2.Traditional sutured anastomosis and sutureless adhesive anastomosis used repectively on the rabbit carotid CASS model after CEA, the formation of neointima were observed at 4hours,l,3,7,30,90days post-opertion. The effects of ICAM-1, MMP-2, apoptosis genes Bax and Bcl-2, and protooncogene c-myc were explored during the course of restenosis.3.In experimental group probucol were gastric gavaged from 14days before CEA to the sampling day (0.6g/Kg/day). The effects of inhibit restenosis of it and mechanisms werestudied by ultrasound and pathology and so on.Results: 1.Animal model completed, soft plaque, hard plaque and ulcer plaque were observed by ultrasound. There are apparently different in blood stream spectrum between model and control group.The peak velocity in systole, minimum velocity in diastole, mean velocity, resistent index and pulsitive index in model group were higher than control group, blood flow were lower than control group.Atherosclerotic fibrous plaque and atheromatous plaque were seen in model group. Pathological measurement showed the average rates of stenosis was 75.42 ± 12.23%, angiography showed the average rates of stenosis was 66.86±8.21%, immunohistochemistry showed the expression of ICAM-1, MMP-2, Bax, Bcl-2 were observed in atherosclerosis plaque, but were not seen in normal arterial wall.2.Several stages could be seen in formation of intima after CEA. The thrombosis could be seen from several hours to3 days after CEA, and the area of thrombosis reached to maximum at 1 day and shrinked at 3 days. The thrombosis post-operation was compsed of fibrin-platelet from sanning electron microscope(SET). The area of thrombosis after sutureless adhesive anastomosis was less than suture anastomsis. The inflammation took place with thrombosis, and could be seen from intima to adventitia, and kept for a period of time from 4 hours to 30 days. The peak of inflammation was seen in 7 days. During earlier period of inflammation granulocytic cells and monocyte-macrophage were seen from SET. The inflammation was more critical in adventita after sutureless adhesive anastomosis than suture anastomsis. New endothelium began to grow from the surrounding over the thin thrombus at 3 days after CEA, and at 7 days new endothelium covered the most endarterectomized segment, and at 30 days endothelium covered completely. The regeneration of endothelium after sutureless adhesive anastomosis was similar to suture anastomsis. VSMC began to proliferate in local media at 3 days, and migrated from media to intima at 7 days, and the neointima reached maxium at 30 days, and media shrinked, andthe degree of proliferation of intima relieved at 90 days. The degree of proliferation of intima after sutureless adhesive anastomosis was less than suture anastomsis. The formation of ECM began at 7 days, and increased to 90 days, and the formation of ECM after sutureless adhesive anastomosis was less than suture anastomsis.The expression of ICAM-1 was seen in VSMC in media at 4 hours, and seen in neointima at 3 days, and reached maxium in neointima at 7 days; the expression of MMP-2 was seen in media at 1 day, and at the peak in neointima at 7 days; the expression of Bcl-2 was seen in intima at 3 days, and reached maxium in neointima at 30 days, and gradually descent following, the expression of Bax was seen in intima at 3 days, and reached maxium in neointima at 7 days, then decreared gradually, and the ratio of Bcl-2/Bax reached maxium at 30 days. In this experiment protooncogene c-myc was analysed at instant pre-operation, 4 hours and Id after CEA by qRT-PCR, and the level of mRNA of c-myc was reached maxium at 4 hours, and decreased following, but still higher than pre-opertion.3.The thickness of neointima and area of neointima and ratio of intima/media in probucol group were less than control group, and the remaining areas of vessels increased, and the degree of stenosis was lower than control group, ultrasound and pathology approved that. Probucol decreased the expression of ICAM-1, MMP-2 and raised the expression of Bcl-2.Conclusions: l.The animal model described before, the rate of completing model and the lesion are stable, CASS animal model can be used in investigation on imitation human lesion. 2.Restenosis after CEA may be repairing response to intima injury, VAMC proliferation, migration, apoptosis and ECM excretion and stack, and cytokine such as ICAM-1, MMP-2 and also genes such as protooncogene c-myc leading function and structure change. 3. The sutureless adhesive anastomosis is more superior than suture anastomsis after CEA. 4. Antioxidant probucol inhibits restenosis after CEA by complicated...
|
PDF Full Text Request