[Effects of some active ingredients of Chinese drugs for activating blood circulation and detoxicating on blood lipids and atherosclerotic plaque inflammatory reaction in ApoE-gene knockout mice].
OBJECTIVE
To observe the effects of active ingredients from Chinese drugs for activating blood circulation and detoxicating, including notoginseng saponins (drug 1), Coptis chinensis (drug 2), giant knotweed rhizome (drug 3) and rhubarb (drug 4), on blood lipids and inflammatory reaction of aortic atherosclerotic plaques in ApoE knockout mice.


METHODS
ApoE knockout mice were fed with high-fat diet for 26 weeks, then they were randomized into 6 groups, the untreated model group and the test groups treated with various test drugs respectively. After ending the 13 weeks of treatment, all the mice were sacrificed with their blood lipids detected, and their heart and aorta were taken out to make slices with paraffin embedding. Four sections from aortic root of each mouse were chosen to measure and calculate the percentage of lipid core (LC) in the total area of plaque (TP) and the lipid/collagen ratio (L/C) in the plaque by HE and Movat staining respectively, and the mean value of the four sections was taken for analysis. The expressions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha) in mice's aorta root were determined by immunohistochemical staining as well.


RESULTS
After being treated for 13 weeks, either the percentage of LC in TP and the L/C ratio was significantly lower in all the test drug treated groups than those in the model group, respectively (P < 0.01), especially prominent in the group treated with drug 3. Although lowering of the two indexes presented in all the 3 groups treated by drug 1, 2 and 3, significant difference still presented between drug 3 treated group vs drug 1 and 2 treated group (P < 0.05). As for the expressions of GM-CSF and TNF-alpha, in comparing with the untreated model group, significant decreasing of the TNF-alpha showed only in the drug 4 treated group, while that of GM-CSF could be found in all the test drug treated groups (P < 0.05).


CONCLUSIONS
All the 4 drugs tested in the recommended dosage can stabilize the vulnerable plaques in ApoE knockout mice by improving the constitution of plaque, among them, drug 3 and 4, the drugs possess both the actions of activating blood circulation and detoxicating, show more significant effect, and their mechanisms may be related to their actions in regulating lipid metabolism and inhibiting inflammatory reaction.
Zhou
Ming-xue
MX
Department of National Integrative Medicine Center for Cardiovasicular Diseases, China Academy of Chinese Medical Sciences, Beijing.
Xu
Hao
H
Chen
Ke-ji
KJ
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D001775:Blood Circulation / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis; D007150:Immunohistochemistry; D008055:Lipids / Q000032:analysis / Q000097:blood*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011897:Random Allocation; D012503:Saponins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D001057:Apolipoproteins E; D004365:Drugs, Chinese Herbal; D008055:Lipids; D012503:Saponins; D014409:Tumor Necrosis Factor-alpha; D016178:Granulocyte-Macrophage Colony-Stimulating Factor