| Along with the enhancement of people's living standard and transformation of life style, atherosclerotic disease has become the most common cause of death[1]. Recent studies show that atherosclerosis is a chronic inflammatory disease, which includes infiltration of inflammatory cells, proliferation of smooth muscle cells, extra cellular matrix accumulation , and eventually plaque rupture. Hypercholesterolemia, hypertension, diabetes, smoking, and other major risk factors for coronary heart disease can damage vascular endothelium, and changes surface characteristics of leukocytes and endothelial cells, promoting an inflammatory response. In the process of atherosclerosis, adhesion molecules expressed by inflamed endothelium recruit leukocytes, including monocytes, which then penetrate into the intima. Inflammatory mediators enhance uptake of modified lipoprotein particles and formation of lipid-filled macrophages. T cells also enter the intima and secrete cytokines, which subsequently amplify the inflammatory response and promote the migration and proliferation of intimal smooth muscle cells. Later in the process, inflammatory mediators can weaken the protective fibrous cap of the atheroma, possibly leading to thrombosis and the occurrence of acute cardiovascular events.Berberine is an isoquinoline alkaloid that has been isolated from Hydrastis Canadensis (goldenseal), Cortex phellodendri (Huangbai) and Rhizoma coptidis (Huanglian).Resent researchs has shown that BBR is a cholesterol-lowering drug distinctly from stain,but the effect of anti-atherosclerotic and stabilization of atherosclerotic plaque is not clear now.This study is to observation efect of Bererine on regressing atherosclerotic plaques, as well as to investigate the possible mechanisms. Method1.Establishment of the rabbit atherosclerosis model Forty New Zealand White Rabbits were randomly grouped into four groups(10/group). Rabbits in the first group were fed standard chow,rabbits in the remaining three group were underwent balloon-induced abdominal aortic wall injury and then fed the cholesterol-rich diet. (a normal chow supplemented with 1 % cholesterol) . group 2 was baseline (without treatment), group 3 was Berberine treatment group(0.1g/kg/d), group 4 was simvastatin intervention group(5mg/kg/d). All rabbits were killed at the end of 12 weeks. before being killed,all rabbits underwent pharmacological triggering with injection of Chinese Russell's viper venom (CRVV) and histamine.2. Detection of indicators(1).Lipid and inflammation mediators measurement:At the baseline and week12, blood samples were collected from all rabbits, respectively. Serum levels of total cholesterol (TC),triglyceride (TG), low density lipoprotein cholesterol (LDLC) and high density lipoprotein cholesterol (HDL-C) were measured. Using enzyme-linked immunosorbent assay(ELISA) to quantify the plasma concentration of different inflammation mediators such as OxLDL,Lp-PLA2,MCP-1,MMP-9 and TIMP-1 in rabbits before pharmacological triggering.(2). The aorta was dissected and excised to observe the occurrence of plaque rupture and thrombosis. The abdominal aorta was processed and examined by hematoxylin and eosin staining. Histopathological slides were analyzed by use of a computer-assisted morphometric analysis system , the intima and Tunica media vasorum thickness were measured .3. Statistic alanalysis: Continuous data are presented as mean±SD. The data are analyzed by analysis of variance(ANOVA),pearson correlate to discuss the factors influencing on plaque score .P<0.05 and P<0.01 was considered statistically significan.Results1. General state of the experimental animals: Has 9 rabbits respectively in group 1 ,2 and group3,and 8 rabbits in group 4 completed the study. Plaque rupture and thrombosis occurred in five rabbits from the remaining nine rabbits in group 2 afterpharmacological triggering, while there were no plaque rupture in the other three groups.2 Lipid measurement: Serum TC,TG and LDL-C levels increaseds ignificantly in the last three groups rabbits following a cholesterol rich diet (all P<0.001), marked increase than group 1.While the levels of TC and LDL-C in Berberine treatment group (group 3) and simvastatin intervention group (group 4) were significantly lower than that in group 2 (all P<0.05). there was no significant difference of lipid profile between group 3 and group 4.3. Plasma concentration of OxLDL,Lp-PLA2,MCP-1 and MMP-9 levels increased significantly in the last three groups rabbits following a cholesterol rich diet (all P<0.001), marked increase than group 1, whereas the levels of TIMP-1 were significantly lower.The level of OxLDL,Lp-PLA2,MCP-1 and MMP-9 had significant difference between plaque ruptured group and nonruptured group (P<0.05), whereas TIMP-1 had no significant difference (I'>0.05). Compared with group 2 (control group), the level of OxLDL,Lp-PLA2,MCP-1 and MMP-9 in Berberine treatment group (group 3) and simvastatin intervention group (group 4) were markedly decreased (P<0.01～0.05), whereas the levels of TIMP-1 were significantly increased.4.Pathologicstaining:Pathologic staining demonstrated that the intima was thin and complete in group 1. A great quantity of widespread fatty plaque were seen in group2 ,in which intima thickened and foam cell accumulated obviously.In contrast, in the berberne prevention group and the simvastatin control group, plaque thickness diminished and both quantity and volume of foam cell decreased. The intima and Tunica media vasorum thickness in group2 were significantly higher than the corresponding values in in the berberne prevention group or the simvastatin control group.The I/M of artery in the group 2 was higher than in the berberine prevention group or simvastatin control group( P<0.01). There was no significent diference between the berberine prevention group and the simvastatin control group (P >0.05)5. There is positive correlation in Plaque score with Plasma concentration of OxLDL,Lp-PLA2,MCP-1 and MMP-9 levels (P<0.01),and negative correlation with TIMP-1(P<0.05). Conclusion 1.Berberine had the effect on decreasing the serum levels of TC,TG ,and LDL-C significantly. At the same time, Berberine can reduce Plasma concentration of OxLDL,Lp-PLA2,MCP-1 and MMP-9 levels, and increase the level of TIMP-1.2. Hypercholesterolemia and inflammation plays a critical role in the formation of atherosclerosis.Measurement of OxLDL,Lp-PLA2,MCP-1,MMP-9 and TIMP-1 in plasma may be seen as Markers of atherosclerosis .3. Berberine had the effect on preventing the formation of the artery atherosclerosis and stabiling vulnerable plaques. Lipid and anti-inflammation mechanisms contribute to the beneficial effects of BBR in artery atherosclerosis formation and in plaque stability.
|
PDF Full Text Request