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AIM: To investigate the relationships between antiproliferative mechanisms of probucol and protein expressions of signaling molecules ERK1/2, MKP-1, HO-1 and Trx-1 in rat aortic smooth muscle cells (RASMCs) stimulated with ox-LDL. METHODS: The effects of probucol on cell cycle, cell proliferation and the expressions of ERK1/2, MKP-1, HO-1 and Trx-1 in the presence of ox-LDL were observed by means of MTT test, FCM and Western blotting. RESULTS: (1) Probucol significantly inhibited the proliferation of RASMCs stimulated with ox-LDL. A value in 100 μmol/L probucol+35 mg/L ox-LDL group was reduced by 34.9% as compared to ox-LDL group (P<0.01). (2) Probucol protected against ox-LDL-induced RASMCs proliferation through inducing cell growth arrest at G_0/G_1 phase and cell apoptosis. (3) ox-LDL increased the expression of p-ERK1/2 by 34.7% (P<0.01) and decreased MKP-1 by 60.0% (P<0.01), respectively, as compared to control. Probucol attenuated the increase in ox-LDL-stimulated p-ERK1/2 level by 15.7%, but increased MKP-1 expression by 2 times (P<0.01). (4)ox-LDL at concentration of 35 mg/L decreased the intracellular Trx-1 expression by 28.9% (P<0.05), and slightly increased the level of HO-1 expression as compared to control (P<0.05). Probucol enhanced the expression of Trx-1 by 91.6% (P<0.01) and HO-1 by 31.9% (P<0.01), respectively as compared to ox-LDL group. CONCLUSION: Probucol inhibits ox-LDL-stimulated the proliferation of RASMCs through increases in MKP-1/HO-1 expression, suppression of cell cycle progression and induction of cell apoptosis.
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Objective To explore the possible immunological mechanism of laminarin sulfate in the prevention of experimental atherosclerosis. Methods Serum soluble interleukin 2 receptor (sIL-2R) , circulating immuno-complex, sub units of T lymphocyte, inter leukin-6(IL-6) , in-terleukin-8(IL-8), tumor necrosis factor-a (TNF-a) and lipid metabolism were determined by ELISA, RIA in rats and quails. Results The lipid metabolism and immunologic function were prominent disturbance in animals after feeding with high-lipid food. However, Laminarin sulfate has obvious regulating effects on above-mentioned index. Conclusions The mechanism of laminarin sulfate in the prevention of atherosclerosis might be closely related to the regulation of the disturbance of lipid metabolism and to the regulation of the immunologic function of the body.
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AIM: To investigate the effect of probucol on proliferation of rat vascular smooth muscle cells(VSMC) stimulated by basic fibroblast growth factor (bFGF) and/or hydrogen peroxide(H 2O 2). METHODS: Effects of probucol on VSMC proliferation and DNA synthesis stimulated by bFGF and/or H 2O 2 were observed by means of MTT test, cell number count and [ 3H]-TdR incorporation. RESULTS: ①Probucol significantly inhibited proliferation and DNA synthesis in VSMC stimulated by bFGF and/or H 2O 2, with dosage-dependent manner. Cell number, A value and [ 3H]-TdR incorporation in group probucol+bFGF and group probucol+H 2O 2 were reduced by 40.0%, 39.1%, 45 5% and 46 9%, 45 0%, 39 5%, respectively, compared with group bFGF and group H 2O 2 ( P 0.05). CONCLUSION: Probucol dramatically inhibited proliferation and DNA synthesis in VSMC stimulated by bFGF and/or H 2O 2, but had no inhibitory effect on the cell proliferation prestimulated by bFGF and /or H 2O 2. [
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The levels of serum lipids, lipoproteins and apoproteins were determined in 36 age over 90 year long-living people, 43 patients with old myocardial infarction (OMI) and 56 normal subjects of the age 40 to 64 years old. The resutts showed that: the ratioes of HDL-c/TC, HDL-c/LDL-c and ApoA_1/ApoB_(100) of the long-living people were higher than that of the patients with OMI; the levels of TC, TG, LDL-c, VLDL-c, ApoB_(100) and ApoA_1 in longevity group were lower than that of OMI group; no significant difference of HDL-c level was found between longevity and OMI group. Compared with normal group, the serum concentration of ApoA_1/ApoB_(100) ratio, TG and VLDL-c in the long-living group were obviously higher, and the serum concentration of ApoB_(100), ApoA_1 and HDL-c significantly lower. No significant differences were found in the levels of TC, LDL-c, and in the ratioes of HDL-c/TC and HDL-c/LDL-c between longevity and normal group. Stepwise regression analysis showed that the serum ApoB_(100) concentration and ApoA_1/ApoB_(100) ratio was the most important factor of longevity. It was suggested that the internal balance of serum lipids and lipoprotein metabolism in long-living people was good co-ordination, and the lower ApoB_(100) level and higher ApoA_1/ApoB_(100) ratio were probably parameters of longevity.
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Objective: To study the attenuating effect of angiotensin I type 1 receptor antagonist losartan and an-giotensin converting enzyme inhibitor captopril on aortic atherosclerosis in rabbits. Methods: Thirty-one male New Zealand rabbits were randomly divided into 5 groups:control group,high cholesterol diet group,losartan group, captopril group and combined drug administration groupdosartan+captopril). The animals were killed after 16 weeks and the serum total cholesterol ,triglyceride, high and low density cholesterol .atherosclertic ratio,endothelin,NO,plaque area percentage,aortic cholesterol content and vascular smooth muscle cell (VSMC) apoptosis were determined. Results:The plaque area percentage,aortic cholesterol contents and endothelin levels of 3 drug treatment groups were significantly lower than that of high cholesterol group,NO contents and VSMC apoptosis were significantly higher. Conclusion:Losartan and captopril can attenuate aortic atherosclerosis induced by high cholesterol diet .combined administration of the 2 drugs at low doses are more effective. The mechanism may be related to the protection of endothelial function and the effect on apoptosis of VSMC.