| Background: The etiology and the mechanism of atherosclerosis(As) is not very clear now, which results in the therapy effect of cardiovascular diseases related with As is limited. Up to now, there are more than three hundred risk factors related with As, including hyperlipidemia, hypertension, diabetes, smoking and infection and so on. These risk factors were identified to damage endothelial cells on the vascular wall, and induce the secretion of many inflammation factors. These inflammation factors may aggravate the injury of endothelial cells, and induce the migration and the proliferation of monocytes/macrophages and smooth muscle cells to the intima, and enlarge the content of extracellular matrix,and regulate the metabolism of lipid on the vascular wall. All of these can promote the occurrence and the progress of As. Most importantly, the inflammation response can make atherosclerotic plaque be unstable and rupture, which will result in clinical cardiovascular symptom. Based on these findings and the hypotheses such as lipid infiltration hypothesis, platelet aggregation ( PA) and thrombosis hypothesis, vascular smooth muscle cell (VSMCs) clone hypothesis, and response-to-injury hypothesis, Ross (1999) and Libby found a novel hypothesis in the pathogenesis of of As: immune inflammation hypothesis. According to the hypothesis, As is a chronic inflammation process in nature. Currently the hypothesis has been recognized extensively and become the authoritative hypothesis which is used to guide the basic research of As. According to the hypothesis, some inflammatory factors such as C Reactive Protein(CRP), CD40/CD40L,TNF-α,ILs, have been used to predict the occurrence of clinical cardiovascular disease and the prognosis after curing. But it is not sure whether anti-inflammation drugs should be used to therapy the diseases related with As. Interestingly, some drugs ,such as tatins, which mainly used to anti-atherosclerosis clinically have anti-inflammation effect besides lowing serum lipid level, which is regarded as one of the important mechanisms to treat the diseases related with As.Thalidomide(Thd) was discovered to be effective for treating vomiting of gestation women as tranquilizer in1950s, but it was obliged to quit drugs market because of severe side-effect of embryo abnormality. After that, Thd was reused to treat immune diseases, tumors, and blood system diseases, due to the effects of Thd on regulation of immune , inhibiting angiogenesis and anti-inflammation. Thd can inhibit the expression of many inflammatory factors such as TNF-α,ILs,COX-2,TGF-β. The mechanism of Thd anti-inflammation is mainly related with inhibiting phosphorylation of I-κB. NF-κB is an important transcription regulation factor, which consists in plasma in complex with I-κB. When leukocytes were activated, I-κB was activated by phosphorylation through signal transduction. Then activated I-κB enters into cell nuclear and bind to DNA box, which enlarge the transcription of inflammatory gene, and many inflammatory factors such as TNF-α,IL-1,IL-6, was induced to secret.Based on the immune inflammation hypothesis of As and the anti inflammation effect of Thd, the project first founded atherosclerotic New Zealand rabbit model by high cholesterol diet, Thd was released by oral at the same time of high cholesterol diet. The effect of Thd anti-atherosclerosis was studied through several indexes.Objective: To Study the effect and the mechanism of Thalidomide prevent atherosclerosis.Methods: Thirty nine New Zealand rabbits were divided into three groups equally.1.Normal diet group; 2.High cholesterol diet group, including 2% cholesterol;3. High cholesterol diet +20mg/kg Thd group. After 2 months, the animals were killed. The whole aorta was stained with Sudan IV, and atherosclerotic plaque size was measured. The atherosclerotic lesion degree was checked after the plaque slice was stained with oil red O and HE. The accumulation of lipid in liver was studied by oil red O stain, and lipid content in liver was detected. Blood was collected at different time points, then the contents of total cholesterol, low density lipoprotein, High density lipoprotein, and Triglyceride were detected by autodetector. The level of tumor necrosis factor alpha was measured by ELISA.Results: 1.The atherosclerotic animal model was founded successfully by high cholesterol diet feeding New Zealand rabbit for two months, which was confirmed by the level of blood TC, LDL, HDL,TG, and Sudan IV stain size, and oil red O stained lipid content, and HE stained lesion size on atherosclerotic plaque slice.2.Compared with high cholesterol group, The atherosclerotic plaque size on the vascular wall in Thd group was lower remarkably((36.7±4.3)% vs(3.2±0.34)%,P<0.05).The number of foam cells and macrophages was decreased, and the content of lipid in plaque was decreased also. All of these indicated that Thd may reduce the degree of atherosclerotic plaque lesion.3. Compared with high cholesterol group, the content of TC, LDL, HDL, TG in Thd group had not statistical difference, which indicated that Thd had no effect on the metabolism of serum lipid.4. Compared with high cholesterol group, the content of lipid in liver in Thd group had no difference, which indicated that Thd had no effect on the metabolism of liver lipid.5. Compared with high cholesterol group, the level of TNF-αin Thd group was decreased remarkably ((0.5204±0.2031) ng/ml vs (1.6727±0.0505) ng/ml),which indicated that Thd maybe had anti-atherosclerosis through lowing the expression of TNF-α.Conclusion: Thalidomide can inhibit atherosclerogenesis. The mechanism of Thd anti-atherosclerosis is no relative with lipid metabolism regulation , mainly due to Thd lowing the expression of TNF-αprobably.
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