[Effects of Xiongshao capsule on the proliferation of vascular smooth muscle cells in rabbits with atherosclerosis].
OBJECTIVE
To study the effects of Xiongshao Capsule (XSC) on the proliferation of vascular smooth muscle cells (VSMC) in rabbits with experimental atherosclerosis (AS), and to explore its possible mechanisms.


METHODS
Rabbit's fractional AS model was established by denuding and injuring the endodermis of abdominal aorta with 4F * Fogarty catheter, followed with feeding of high cholesterol forage. The animals were randomly divided into 8 groups, the model groups of 3 days, 2 weeks and 6 weeks after modeling (Group A, B and C); the single endothelium injury group (Group D), the probucol treated group (Group E), the low-dose and high-dose XSC treated groups (Group F and G) and the sham operative group (Group N). All were fed with high fat forage except those in Group N and D. The proliferative activity of neogenetic SMC at abdominal aorta with the most obvious pathological changes was analyzed by proliferating cell nuclear antigen immunohistochemical method; the VSMC phenotypic modulation was detected by transmission electron microscope (TEM), and the level of plasma angiotensin (Ang II) was measured by radioimmunoassay. And the effects of treatment on them were observed as well.


RESULTS
The plasma Ang II level elevated gradually in Group A, and showed significant difference as compared that between Group C and Group N (P < 0.01); as compared with Group C, that in Group G was reduced significantly (P < 0.05); a reducing tendency was shown in Group E and F, but the difference of them with Group C was insignificant. Immunohistochemical dyeing showed that PCNA positive expressing cell was not found in the blood vessels of Group N, few was seen in Group A, while the upmost positive expression was shown in Group B, as for in Group C, significantly thickened endomembrane appeared, but the PCNA positive expression dropped. Number of PCNA positive cells reduced significantly (P < 0.05) in the drug treated groups, especially in Group G, showing significant difference as compared with that in Group C (P < 0.05, P < 0.01). TEM demonstrated normal shaped VSMC of aortic medial tunica in Group N, basically normal in Group A, but in Group B, migration of VSMCs into intima was found, as for in Group C, abundant lipid granules and bigger vacuoles appeared in VSMCs with markedly proliferated intercellular collagenous fibers. Synthetic transformation could also be found in Group D. The transform VSMCs in neogenetic endothelium was fewer in the drug treated groups than that in Group C. Morphology of VSMC was basically normal in Group G, with few intercellular collagenous fiber proliferation, while in Group E and F, many lipid droplets in VSMC and lot of collagenous fibers proliferation in intercellular space still retained.


CONCLUSIONS
XSC can prevent the genesis and development of AS through significantly lowering the plasma Ang II level and inhibiting the migration and proliferation of VSMC.
Xu
Feng-Qin
FQ
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing. xufengqin2000@yahoo.com.cn
Xu
Hao
H
Liu
Jian-Gang
JG
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D002214:Capsules / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011817:Rabbits
D002214:Capsules; D004365:Drugs, Chinese Herbal; D018809:Proliferating Cell Nuclear Antigen; C528128:xiongshao; D000804:Angiotensin II