[Inhibitory effect and acting mechanism of Tongxinluo on IL-1beta-mediated coronary intimal hyperplasia and 5-hydroxytryptamine-induced coronary vasospasm in small swine].
OBJECTIVE
To observe the inhibitory effect of Tongxinluo (TXL) on coronary vaso spasm in small swine in vivo, and to investigate its possible acting mechanism.


METHODS
The model of coronary atherosclerosis in 16 male small swines was established by left thoracotomy after anesthesia, isolated the sections of left anterio-descending branch and proximal end of rotator branch with similar outer diameter, and encapsulated them with paper-towel holding 2.5 microg interleukin-1beta. Two weeks later, the condition of coronary vasospasm induced by catheter intra-coronary injection of 5-hydroxytryptamine (5-HT, 10 microg/kg) was observed through coronary artery contrast examination. The 12 swines with successfully formed coronary vaso spasm were randomly divided into 2 groups, the TXL group and the control group. They were fed with special diet, but TXL 1 g/(kg d) was administered additionally to the TXL group for 4 weeks. The observation on coronary vasospasm was repeated 1 week after discontinuation of TXL treatment, then the animals were sacrificed, their vascular sections enclosed with IL-1beta was taken to conduct the pathologic examination and to detect the expressions of Rho kinase mRNA and its substrate myosin- binding subunit phosphorylation (MBS-P) by RT-PCR and Western blot method.


RESULTS
Coronary artery contrast showed that local coronary stenosis occurred in the 12 model swines to different extents (20% - 30%, and vascular spasm on them could be induced by 5-HT. At the time of repeating examination, 11 vascular sections in the control group still maintain their positive spasm reaction to 5-HT, but only 2 in the TXL group did so, the reaction turned to negative in 1 and 10 in the two groups respectively. Pathological examination showed that different degrees of macrophage aggregation could be found in both groups. The degree of lumen stricture and endometrial hyperplasia in the TXL group was obviously attenuated than those in the control group. The expressions of Rho kinase mRNA and MBS-P in the control group were up-regulated obviously. As compared with those in the control group, they were inhibited significantly in the TXL group, as (71.5 +/- 2.4) vs (98.2 +/- 7.7)% and 16,633 +/- 1,390 vs 25,818 +/- 4,745, respectively (all P < 0.05).


CONCLUSIONS
TXL could obviously inhibit the coronary intimal hyperplasia mediated by IL-1beta and coronary vasospasm induced by 5-HT, one of its mechanisms is possibly the inhibition on the intracellular Rho kinase mRNA expression in the IL-1beta enclosed vascular section to decrease the level of MBS-P.
Guan
Qi-Gang
QG
Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang. gqg74725@sina.com
Zeng
Ding-Yin
DY
Sun
Xi-Zhuo
XZ
D000818:Animals; D003329:Coronary Vasospasm / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D008297:Male; D011897:Random Allocation; D012701:Serotonin / Q000009:adverse effects*; D013552:Swine; D054460:rho-Associated Kinases / Q000235:genetics / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D012701:Serotonin; D054460:rho-Associated Kinases