Effect of QiShenYiQi pill on myocardial collagen metabolism in experimental autoimmune myocarditis rats.
OBJECTIVE
To observe the effect of QiShenYiQi pill (QSYQ) on myocardial collagen metabolism in experimental autoimmune myocarditis rats, and to explore its mechanism of action.


METHODS
Lewis rats underwent the injection of myocardial myosin mixed with freund's complete adjuvant were randomized into three groups: model, valsartan and QSYQ groups. And we treated rats which were injected phosphate buffered saline (PBS) mixed with freund's complete adjuvant as control group. Rats were intervened and euthanized at 4 and 8 weeks. We use alkaline hydrolysis to detect the content of myocardial hydroxyproline (HYP), and ELISA to detect the level of serum procollagen type I carboxyterminal peptide (PICP), procollagen type III amino-terminal peptide (PIIINP), and collagen C telopeptide type I (CTX-I). Myocardial MMP-1 and TIMP-1 protein expression was detected by immunohistochemistry, and myocardial MMP-1 and TIMP-1 mRNA expression was detected by real-time qPCR.


RESULTS
QSYQ reduced the content of myocardial HYP, and this reduction was greater over time. QSYQ also reduced the serum concentration of PICP, PIIINP, CTX-I and the PICP/PIIINP ratio, which further reduced over time, whereas its effect on lowering PICP was significantly greater than that of valsartan at 4 and 8 weeks, and lowering CTX-I was significantly greater than that of valsartan at 8 weeks. In addition, after 4 weeks, QSYQ enhanced the protein and mRNA expression of MMP-1 and TIMP-1, and its effect on highering TIMP-1 was significantly greater than that of valsartan, whereas there was no significant difference in the expression of myocardial MMP-1 or TIMP-1 at 8 weeks. QSYQ reduced the ratio of MMP-1/TIMP-1, which further reduced over time, and the effect of QYSQ was significantly greater than that of valsartan after 4 weeks.


CONCLUSIONS
This study provides evidence that QSYQ can reduce the rate of myocardial collagen synthesis and degradation. It also effectively improved the degree of myocardial fibrosis in experimental autoimmune myocarditis rats and it had a tendency to have a greater effect with longer treatment duration, which is related to the mechanism of regulation of MMP-1 and TIMP-1 expression in the myocardial rat.
Department of Geriatric Medicine, First Teaching Hospital of Tianjin University of Traditional Chinese Medcine, 314 An Shan Xi Road, Nan Kai District, Tianjin, 300193, China.
Shi-Chao
SC
Lv
Tianjin University of Traditional Chinese Medcine, 312 An Shan Xi Road, Nan Kai District, Tianjin, 300193, China.
Meifang
M
Wu
Tianjin University of Traditional Chinese Medcine, 312 An Shan Xi Road, Nan Kai District, Tianjin, 300193, China.
Meng
M
Li
Tianjin University of Traditional Chinese Medcine, 312 An Shan Xi Road, Nan Kai District, Tianjin, 300193, China.
Qiang
Q
Wang
Tianjin University of Traditional Chinese Medcine, 312 An Shan Xi Road, Nan Kai District, Tianjin, 300193, China.
Xiao-Jing
XJ
Wang
School of Integrative Medicine, Tianjin University of Traditional Chinese Medcine, 312 An Shan Xi Road, Nan Kai District, Tianjin, 300193, China.
Ao
A
Zhang
Tianjin University of Traditional Chinese Medcine, 312 An Shan Xi Road, Nan Kai District, Tianjin, 300193, China.
Ling
L
Xu
Department of Geriatric Medicine, First Teaching Hospital of Tianjin University of Traditional Chinese Medcine, 314 An Shan Xi Road, Nan Kai District, Tianjin, 300193, China. Electronic address: tjzhtcm@163.com.
Jun-Ping
JP
Zhang
D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D009205:Myocarditis / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D059748:Proteolysis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011917:Rats, Inbred Lew; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; C528580:qishen yiqi; D003094:Collagen; D020781:Matrix Metalloproteinase 1; D006909:Hydroxyproline
Collagen metabolism; Experimental autoimmune myocarditis; QiShenYiQi pill