Effect Of IIFs On Atherosclerotic Rabbits And Preventive Funtion Of Total Saponins Of Panax Notoginseng

Atherosclerotic cardio-cerebral vascular diseases are still the most serious hazard to people's health and life. Epidemic and clinical investigation showed about 50% patients with AS whose serum lipid level was normal, the incidence of AS remained significiant increase in all world although the drug of anti-hyperlipermia have been applied widely, which showed other etiological factors palyed important role in AS. Inflammatory and immunological factors (IIFs) level were significantly increased in AS patiets, and the patients with chronic inflammatory disease whose incidence of AS was increased, which obviously indicated that IIFs played key role in the pathogenesis of AS. But until now, the studies about IIFs were limited, which difficult to reveal the relationship and rule between IIFs and AS. So, we established durative inflammatory AS model, and contrasted the change of IIFs and pathology alteration of atherosclerotic plaque during atherosclerogenesis in rabbits between durative inflammatory AS model and cholesterol-fed AS model, observed the effect of relieved inflammatory response on the formation of AS, and explored the function of IIFs in AS by experiment firstly. At the same time, studied the relationship between preventive function of total Saponins of Panax Notoginseng (PNS) and inflammatory and immunological modulation to aim at clarifying the mechanism of anti-AS by PNS and developing new spaces about new anti-AS drug including anti-hyperlipermia, anti-throm, as well as inflammatory and immunological modulation. METHODS: Intraperitoneal injected rabbits different dose of Zymosan (30,10,5mg /kg), and counted WBC and NEUT percent then found the right dose and interval ip Zymosan, rabbits durative inflammatory model was established. Rabbits durative inflammation AS model was set up by durative inflammatory factors combined with cholesterol-fed AS model. Compared the extent of aortic atherosclerotic plaque (measured by planimetry of the sudanophilic area), and the pathologic alteration (observed by light microscope) between durative inflammation AS model and cholesterol-fed AS model. 44 male rabbits were divided into five groups. Control group (rabbits were fed regular food, 120-150g /d), cholesterol-fed AS group (high lipid diet 120-150g /d, cholesterol, egg and fat included), durative inflammation AS group (high lipid diet 120-150g /d and Zymosan ip 10mg/kg/48h), Aspirin group (high lipid diet 120-150g /d plus Aspirin 12mg /kg /d and Zymosan ip 10mg/kg/48h), PNS preventive group (high lipid diet 120-150g /d plus PNS 120mg /kg /d and Zymosan ip 10mg/kg/48h). Experiment lasted 8 weeks. The content of interleukin (IL-6), C-reactive protein (CRP), circulating immune complex (CIC), Nitrogen monoxide (NO) and superoxide dismutase (SOD) in serum were detected respectively, IgG contained in the atherosclerotic plaque were investigated by immunohistochemistry technique. The extent of aortic atherosclerotic plaque was measured by planimetry of the sudanophilic area, and the pathologic alteration was observed by light microscope. RESULTS: 1. Rabbits were intraperitoneal injected Zymosan with 10mg /kg, the counts of WBC and the percent of NEUT increased significantly during 24h, and remained the high level until 48h, the counts of WBC and the percent of NEUT begined to decrease at 72h. Zymosan i.p at 48h again could remainde the high level of WBC and NEUT until 72h and 96h. The dose of 10mg /kg resulted in rabbits death and 5mg /kg coulded stimulate the inflammatory respond. 2. Combined durative inflammatory factors with cholesterol-fed AS model, the durative inflammatory AS model was established successfully by ourselvies, the area of aortic AS in durative inflammatory AS model was significant larger than cholesterol-fed AS model. Aorta revealed that marked alteration and the severity in the aortic wall of durative inflammatory AS model was also more serious. 3. The content of IL-6, CRP and CIC in cholesterol-fed AS groups were increased, and the content in durative inflammatory AS group were increased significantly compared with cholesterol-fed AS group (P<0.01). The content in PNS group and Aspirin group were decreased compared with AS model groups (P<0.01 or 0.05). IgG in the atherosclerotic plaque demonstrated yellow or brown-yellow sediment in aortic intimal layer, and the stain in durative inflammatory AS group was the most intensive, in PNS group and Aspirin group was thin.4. The content of NO and SOD were both decrease in cholesterol-fed AS group, and the content in durative inflammatory AS group were decreased significantly compared with cholesterol-fed AS group (P<0.01). The content in PNS group were both increasd compared with AS model groups (P<0.01). The content in Aspirin group were increased compared with durative inflammatory AS group, there was significant difference compared with cholesterol-fed AS group at the 8th weekend (P<0.01). CLNCLUSION: 1. Durative inflammatory model was established by Zymosan ip with the dose of 10mg /kg after each 48 houres interval. 2. Rabbits durative inflammatory AS model was established firstly by combined durative inflammatory factors with cholesterol-fed AS model. 3. Compared with cholesterol-fed AS model, the pathological changes occured earlier and more serious, the content of IL-6, CRP, CIC and IgG were increased, but the anti-inflammation factors such as NO and SOD were decreased in durative inflammatory AS model. Which indicated that IIFs and the inflammatory and immune responses resulted from IIFs had important function in AS. 4. The function of inflammatory and immunological modulation of PNS was the important mechanism and effective pathway to prevent AS, which had the important directive meaning to apply the resourse of chinese traditional medicine reasonably such as PNS.