[Molecular mechanism of effect of wenban humai granule on stability of atheromatous plaque].
OBJECTIVE
To explore the molecular mechanism of wenban humai granule (WHG) in stabilizing atheromatous plaque, by observing its effect on the collagen degradation and synthesis imbalance manner in the fibrous cap of the plaque.


METHODS
Atherosclerosis (AS) rabbit model established by feeding high fat diet. The changes of protein and mRNA expression of macrophage CD68, metalloproteinase-1 (MMP-1), alpha-smooth muscle actin (alpha-SMA) and collagen I (C-I) in model rabbits' neo-genesic intima were determined by immunohistochemical stain and in situ hybridization methods before and after treatment as well as before and after modeling.


RESULTS
After being fed with high fat diet for 7 weeks, the protein and mRNA expression of macrophage CD68, MMP-1 in neo-genesic intima of aorta in the model rabbits significantly increased, these changes could be significantly restored after 8 weeks treatment with WHG or simvastatin. At the same time, the expressions of alpha-SMA protein and C-I protein and mRNA slightly increased due to the immigration of SMC in aortic media to neo-genesic intima, these expressions could be further increased after WHG treatment but showed a reducing trend after simvastatin treatment (P < 0.05 and P < 0.01). In the whole course, positive correlation was shown between protein expressions of CD68 and MMP-1 (r = 0.952, P < 0.01) and also between these of alpha-SMA and C-I (r = 0.793, P < 0.01).


CONCLUSIONS
WHG affects the collagen degradation and synthesis imbalance in the fibrous cap of the plaque to stabilize plaque through bi-directional regulation, up-regulating synthesis thesis factors and down-regulating degradation factors, while simvastatin perform its action on plaque stability by down-regulating degradation factors alone.
Zhang
Bao-ting
BT
Department of TCM, Shanhai Tenth People's Hospital, Tongji University, Shanghai 200072. zbtzg@vip.sina.com
Yan
Qian-lin
QL
Yan
De-xin
DX
Li
Zhi
Z
Yu
Yong-chun
YC
Huang
Guo-ping
GP
Tang
De-sheng
DS
Ye
Xin
X
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001011:Aorta / Q000473:pathology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D008264:Macrophages / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D003094:Collagen; D004365:Drugs, Chinese Herbal; D020781:Matrix Metalloproteinase 1; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule