Effects And Mechanism Of SuXiao JiuXin Wan On Experimental Atherosclerosis

Objective:To investigate the anti-atherosclerosis effects of SuXiao JiuXin Wan and its possible mechanism through animal model of experimental atherosclerosis.Method:Experimental atherosclerosis in rats was produced by feeding with atherogenic-diet and vitaminD₃ administration(600,000 IU/kg by intraperitoneal injected at one time)for 12 weeks.60 male mature Sprague-Dawlay rats were divided into 6 groups randomly and equally:1.normal group(normal diet);2.AS model group (atherogenic-diet);3.SXL group(atherogenic-diet and SX 60mg·kg^-1·d^-1);4.SXM group(atherogenic-diet and SX 600mg·kg^-1·d^-1);5.SXH group(atherogenic-diet and SX 1800mg·kg^-1·d^-1);6.Astorvastatin group(atherogenic-diet and Astorvastatin 4mg·kg^-1·d^-1).SX or Astorvastatin was given by gavage from the beginning of the first week to the end of the experiment.At the same time,normal saline was given to the rats of normal group and model group with the same volume and the same way. After 12 weeks treatment,all rats were killed,Aortas were taken and sectioned. Hematoxylin and eosin(H&E),masson were used for morphological investigation by light microscope.The changes of aortas' ultrastructure were observed by electron microscope.Blood was collected to detect the levels of serum total cholesterol(TC), triglyceride(TG),low density lipoprotein(LDL),high density lipoprotein(HDL), malonaldehyd(MDA),superoxide dismutase(SOD)by biochemistry method.The serum levels of oxidized low lipoprotein were mearsured by enzyme-linked immunosorbent assay(ELISA)method.The expression of ATP binding cassette transporter A1(ABCA1)and heme oxygenase-1(HO-1)on aorta were examined by immunohistochemistry.Results:1.Pathomorphological changes in the aorta(1)Pathologic staining:HE stain:In the normal group,the structure of the aortic wall was well-constructed.The intima was thin and endothelia were intact.The smooth muscle cells didn't proliferate.In the model group,Some endothelial ceils were lost and the intima thicked.The smooth muscle ceils proliferated and lined up in disorder.The structures and arrangements of elastic fibers were in disorder and the fibrous tissues proliferated.Compared with the model group,the pathological changes lessened in the SXM,SXH and ATO groups.(2)Masson stain:In the normal group,the structures and arrangements of elastic fibers were intact and in order.In the model group,the vascular smooth cells and collagen fibers proliferated significantly. Compared with the model group,the extents of these changes lessened obviously in the SXM,SXH and ATO groups.(2)Electron microscope examination:In the model group,aortic tunica intima was destroyed and thicked,the structure arrangement was disorder as well.There were mass foam cells between tunica intima and runica media,furthermore,there were some fatty vesicles in intima.The smooth muscle cell proliferated greatly.Compared with the model group,the pathological changes of aortic ultrastructure alleviated obviously in the SXM,SXH and ATO groups2.In the model group,TC,TG,LDL and HDL were increased compared with the normal group(P＜0.05).Compared with the model group,the serum lipid profile did not change appreciably in the SXL group(P＞0.05),while the levels of TC,TG and LDL were declined and the level of HDL was increased evidently in the SXM,SXH and ATO groups(P＜0.05).SXH group has the best results among the three SX treatment groups.In the model group,the serum SOD activity was declined and the MDA,ox-LDL level were increased compared with the normal group(P＜0.05).Compared with the model group,the serum SOD,MDA,and ox-LDL level did not change appreciably in the SXL group(P＞0.05),while the serum SOD activity was increased and the MDA,ox-LDL level were decreased definitely in the SXM,SXH and ATO groups(P＜0.05).3.The expression of ABCA1of aortic in the model group was enhanced compared with the normal group(P＜0.05).Compared with the model group,the expression of ABCA1 of aortic was not influenced in the SXL,SXM groups(P＞0.05),while,it was increased in the SXH group and decreased in the ATO group.(P＜0.05).4.The expression of HO-1 of aortic in the model group was enhanced compared with the normal group(P＜0.05).Compared with the model group,the expression of HO-1 of aortic was not influenced in the SXL group(P＞0.05),while,it was increased in the SXM,SXL and ATO group(P＜0.05).Conclusions:The rat model of early atherosclerosis can be established successfully by atherogenic-diet and vitamin D₃ administration(600,000 IU/kg by intraperitoneal injected at one time).The results suggest that the SuXiao JiuXin Wan can ameliorate the atherosclerotic changes and its protection effect may be involve in regulating plasma lipid metabolic disorder,enhancing anti-oxidant capacity and so on. (1)SX has obvious effect on decreasing the serum levels of TC,TG,LDL,MDA and ox-LDL,and increasing the serum level of HDL,SOD in AS rats;(2)SX can increase the expression of ABCA1,HO-1 of aortic;(3)Morphological changes of aorta show a significant effect of protecting aorta endothelial cell,decreasing the proliferation of vascular smooth muscle cell and collagen fibers in AS rats.