| ObjectiveTo observe the clinical effect of heat-clearing-detoxicating and activating-blood method of traditional Chinese medicine on atherosclerotic vulnerable plaque by the animal experiment and clinical research. And to observe the inflammatory cytokines, especially CD40-CD40L signal pathway in order to explore the possible mechanism of stabilizing the atherosclerotic vulnerable plaque.Methods(1) Experimental Study:To establish forty vulnerable plaque model by injuring the rabbits'abdominal-thoracic aorta intima with the balloon-injured angioplasty through femoral artery at the second week, then followed with high cholesterol feeding beginning at the third week. Then the forty New Zealand white model rabbits were randomly divided into four groups:model control group (n=10), the simvastatin treating group (n=10), small-dose Jiedu-huoxue group(n=10), large-dose Jiedu-huoxue group (n=10).At the third week, first of drug interventions were added during the process. And there was a normal control group those were ten healthy male New Zealand white rabbits fed with standard feed. At the beginning of the experiment and the10th week, blood samples were collected for measuring the lipid profile. After ten weeks,to observe the morphology of the atherosclerotic vas and make a pathological analysis, and to test the expression of ICAM-1and TNF-a in the artery with immunohistochemistry. And the concentrations of sCD40L,ICAM-1, TNF-a, IL-1β on blood serum were measured using the ELISA method. The mRNA expressions of IL-1β, CD40in the arterial atherosclerosis lesions were measured using the real time fluorescence quantitative PCR.(2) Clinical study:114patients with acute myocardial infarction and emergency coronary artery angiography were randomly divided into3groups:A treatment group (38cases, basic thtrapy of western medicine plus heat-clearing and activating-blood decoction), B treatment group(38cases, basic thtrapy of western medicine plus activating-blood decoction),C control group(38cases, basic thtrapy of western medicine). The3groups were treated for2weeks. The score of TCM symptoms were recorded in the1d,7d,14d. At the beginning of the experiment and the14d, blood samples were collected for measuring the concentrations of hs-CRP, Fib, PAgT.Results(1) Experimental Study:the HE staining showed the aortic tissue structure of normal control group is normal. The vulnerable plaque animal model was successfully established by balloon injuring and high cholesterol feeding. The aortic plaques of large-dose Jiedu-huoxue group and simvastatin group showed characteristics of stable plaque. Large-dose Jiedu-huoxue group observably inhibited the immunohis-tochemical expression of ICAM-1and TNF-a in the atherosclerotic plaque. Compared with the model control group and the simvastatin treating group, The mRNA expressions of IL-1β in the arterial atherosclerosis lesions of large-dose Jiedu-huoxue group were lowerd and the differences were significant (P<0.05). Compared with the model control group, the concentrations of ICAM-1,IL-1β on blood serum of large-dose Jiedu-huoxue group were lowerd and the differences were significant (P<0.05), but compared with the simvastatin treating group the differences were no significant (P>0.05). The each intervention group compared with the model group, can reduce serum TNF-a, sCD40levels, there was a significant difference (P<0.05), the intervention group comparison each ather, the simvastatin group have a trend to furtherly reduce the level of serum TNF-a. The mRNA expressions of CD40in the arterial atherosclerosis lesions of large-dose Jiedu-huoxue group were lowerd, compared with the model control group, there were significant differences (P<0.05). The expressions of CD40of large-dose Jiedu-huoxue grou close to normal control group, there were no significant differences(P>0.05). While the low-dose Jiedu-huoxue group and simvastatin group can't significantly affect the mRNA expressions of CD40, compared with the model control group, here were no significant differences(P>0.05). The low-dose Jiedu-huoxue group compared with the model control group, can decrease the concentrations of sCD40L and TNF-a, there was a significant difference (P<0.05). The lipid regulating aspects, especially to reduce LDL-C, the simvastatin group is better than the large-dose Jiedu-huoxue group and low-dose Jiedu-huoxue group.(2)Clinical study:The "heat-toxic" symptoms were obvious in the patients with acute myocardial infarction in acute phase. Compared with B treatment group and C control group, the scores of TCM symptoms such as the points of dry mouth, bitter mouth, irritability, short yellow urine, dry stool and the total score of symptoms were obviously lower in A treatment group(P<0.05). But there was no significant difference between B treatment group and C control group. The rate of total efficiency and significant of A treatment is superior to B treatment group and C control group, there were significant differences (P<0.05). The concentrations of hs-CRP,PAgT on blood serum of A treatment group were lower than B treatment group and C control group(P<0.05). But there was no significant statistical difference on the concentrations of Fib on blood serum in the three groups(P>0.05).Three groups had no obvious adverse reaction.ConclusionAnimal experiments indicated that injuring the rabbits' abdominal-thoracic aorta intima with the balloon-injured angioplasty and high fat feeding method can successfully establish animal model of vulnerable plaque. On the effects of stabilizing vulnerable plaque, large-dose Jiedu-huoxue group may be superior to simvastatin group and low-dose Jiedu-huoxue group. Heat-clearing-detoxicating and Activating-Blood Method can reduce the expression of inflammatory factors, and stabilize the vulnerable plaque in the animal models, and the outcome was positively related to the concentrations of Jiedu-huoxue decoction. Heat-clearing-detoxicating and Activating-Blood Method possibly adjust, rather than completely block the CD40/CD40L system in vulnerable plaques, reduce the levels of CD40, sCD40, TNF-a, ICAM-1, IL-1,and has effects of ant-inflammatory factor to stabilize vulnerable plaque.Clinical studies show that heat-clearing and activating-blood decoction can obviously improve the "heat-toxic" symptoms of traditional Chinese medicine in acute myocardial infarction patients, decrease the levels of hs-CRP, PAgT levels, reduce the trends of blood viscosity, reduce Possibility of thrombosis after stente.Therefore, Heat-clearing-detoxicating and Activating-Blood Method has the effects of anti-inflammatory, can stabilize vulnerable plaque. |
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